Progesterone Within Ovulatory Menstrual Cycles Needed for Cardiovascular Protection: An Evidence-Based Hypothesis
Prior JC, 2014
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Chronic endometritis in women with recurrent early pregnancy loss and/or fetal demise
McQueen DB et al., 2014Fertility and sterility
To assess the prevalence of chronic endometritis in women with a history of recurrent early pregnancy loss (REPL) and/or fetal demise (FD). Observational cohort study using prospectively collected data. Recurrent pregnancy loss program in an academic medical center. PATIENT(S): Three hundred ninety-five women with a history of two or more pregnancy losses of less than 10 weeks' size or a fetal demise of 10 or more weeks' size. INTERVENTION(S): All women had an endometrial biopsy. Chronic endometritis was treated with antibiotics, and a second endometrial biopsy was recommended as a "test of cure." MAIN OUTCOME MEASURE(S): Subsequent live-birth rate (LBR). RESULT(S): The overall prevalence of chronic endometritis was 9% (35/395) in this cohort; 7% (21/285) in the REPL group, 14% (8/57) in the FD group, and 11% (6/53) in the combined REPL/FD group. The cure rate was 100% after a course(s) of antibiotics. The subsequent cumulative LBR was 88% (21/24) for the treated chronic endometritis group versus 74% (180/244) for the group without chronic endometritis. The per-pregnancy LBR for the treated chronic endometritis group was 7% (7/98) before treatment versus 56% (28/50) after treatment. CONCLUSION(S): There was a high prevalence of chronic endometritis in this cohort. The test of cure was 100% with antibiotics. Subsequent LBRs after treatment were encouraging.
Oral contraceptives and breast cancer risk overall and by molecular subtype among young women
Beaber EF et al., 2014Cancer Epidemiol Biomarkers Prev
Evidence suggests that recent oral contraceptive (OC) use is associated with a small increased breast cancer risk; yet risks associated with contemporary OC preparations and by molecular subtype are not well characterized. We conducted a population-based case-control study of invasive breast cancer among women ages 20 to 44 residing in the Seattle-Puget Sound area from 2004 to 2010 (985 cases and 882 controls). We collected information on contraceptive use and participant characteristics via an in-person interview. Multivariable-adjusted logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Lifetime duration of OC use for ≥ 15 years was associated with an increased breast cancer risk (OR, 1.5; 95% CI, 1.1-2.2). Current OC use (within 1 year of reference date) for ≥ 5 years was associated with an increased risk (OR, 1.6; 95% CI, 1.1-2.5) and there were no statistically significant differences in risk by OC preparation. Risk magnitudes were generally greater among women ages 20 to 39, and for estrogen receptor-negative (ER(-)) and triple-negative breast cancer (current use for ≥ 5 years among ages 20-39: ER(-) OR, 3.5; 95% CI, 1.3-9.0; triple-negative OR, 3.7; 95% CI, 1.2-11.8), although differences between groups were not statistically significant. Long-term use of contemporary OCs and current use for ≥ 5 years was associated with an increased breast cancer risk among women ages 20 to 44. Risk may be greater among younger women and for ER(-) and triple-negative breast cancer, but these findings require confirmation. Continued surveillance and pooled analyses of OC use and breast cancer risk by molecular subtype are needed as OC preparations evolve.
Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae--2014
No Authors Listed, 2014MMWR Recomm Rep
This report updates CDC's 2002 recommendations regarding screening tests to detect Chlamydia trachomatis and Neisseria gonorrhoeae infections (CDC. Screening tests to detect Chlamydia trachomatis and Neisseria gonorrhoeae infections-2002. MMWR 2002;51[No. RR-15]) and provides new recommendations regarding optimal specimen types, the use of tests to detect rectal and oropharyngeal C. trachomatis and N. gonorrhoeae infections, and circumstances when supplemental testing is indicated. The recommendations in this report are intended for use by clinical laboratory directors, laboratory staff, clinicians, and disease control personnel who must choose among the multiple available tests, establish standard operating procedures for collecting and processing specimens, interpret test results for laboratory reporting, and counsel and treat patients. The performance of nucleic acid amplification tests (NAATs) with respect to overall sensitivity, specificity, and ease of specimen transport is better than that of any of the other tests available for the diagnosis of chlamydial and gonococcal infections. Laboratories should use NAATs to detect chlamydia and gonorrhea except in cases of child sexual assault involving boys and rectal and oropharyngeal infections in prepubescent girls and when evaluating a potential gonorrhea treatment failure, in which case culture and susceptibility testing might be required. NAATs that have been cleared by the Food and Drug Administration (FDA) for the detection of C. trachomatis and N. gonorrhoeae infections are recommended as screening or diagnostic tests because they have been evaluated in patients with and without symptoms. Maintaining the capability to culture for both N. gonorrhoeae and C. trachomatis in laboratories throughout the country is important because data are insufficient to recommend nonculture tests in cases of sexual assault in prepubescent boys and extragenital anatomic site exposure in prepubescent girls. N. gonorrhoeae culture is required to evaluate suspected cases of gonorrhea treatment failure and to monitor developing resistance to current treatment regimens. Chlamydia culture also should be maintained in some laboratories to monitor future changes in antibiotic susceptibility and to support surveillance and research activities such as detection of lymphogranuloma venereum or rare infections caused by variant or mutated C. trachomatis.
Choice of lumbar spine bone density reference database for fracture prediction in men and women: a population-based analysis
William D Leslie et al., 2014J Clin Densitom
The diagnosis of osteoporosis in men is controversial, although most studies demonstrate similar fracture rates for men and women with the same level of hip bone mineral density (BMD). Whether this applies to the lumbar spine is currently uncertain and has important implications with respect to choice of reference population for T-score calculation and osteoporosis diagnosis. This question was specifically addressed in the population-based Canadian Multicentre Osteoporosis Study cohort of 4745 women and 1887 men ages 50+ yr at the time of baseline lumbar spine dual energy x-ray absorptiometry. In up to 10 yr of observation, incident clinical major osteoporotic fractures occurred in 110 men (5.8%) vs 543 women (11.4%) (p < 0.001). Mean lumbar spine BMD in men was greater than in women, both among those with and those without incident major osteoporotic fracture (p < 0.001). Men were at slightly lower risk for incident major osteoporotic fracture than women for an equivalent lumbar spine BMD (ageand BMD-adjusted rate ratio 0.75, 95% confidence interval 0.60-0.93, p = 0.008) with similar findings after adjustment for the World Health Organization fracture risk assessment clinical risk factors or competing mortality. No significant sex difference in the BMD relationship was seen for vertebral fractures (clinical or radiographic) or for all fractures. In summary, this large population-based longitudinal cohort study found similar or lower fracture risk for men vs women after adjustment for absolute lumbar spine BMD and additional covariates. The least complicated model for describing fracture risk is therefore to use the same reference lumbar spine data for generating T-scores in men and women.
Luteal phase deficiency in regularly menstruating women: prevalence and overlap in identification based on clinical and biochemical diagnostic criteria
Schliep KC et al., 2014J Clin Endocrinol Metab
Although adequate luteal hormone production is essential for establishing pregnancy, luteal phase deficiency (LPD) is poorly characterized among eumenorrheic women. We assessed the prevalence and overlap of two established short luteal phase duration less than10 days (clinical LPD) and suboptimal luteal progesterone of 5 ng/mL or less (biochemical LPD) and their relationship with reproductive hormone concentrations. Design, Setting, We conducted a prospective study in western New York (2005-2007) following 259 women, aged 18-44 years, for up to two menstrual cycles. Among ovulatory cycles with recorded cycle lengths (n = 463), there were 41 cycles (8.9%) with clinical LPD, 39 cycles (8.4%) with biochemical LPD, and 20 cycles (4.3%) meeting both criteria. Recurrent clinical and biochemical LPD was observed in eight (3.4%) and five (2.1%) women, respectively. Clinical and biochemical LPD were each associated with lower follicular estradiol (both P ≤ .001) and luteal estradiol (P = .03 and P = .02, respectively) after adjusting for age, race, and percentage body fat. Clinical, but not biochemical, LPD was associated with lower LH and FSH across all phases of the cycle (P ≤ .001). Clinical and biochemical LPD were evident among regularly menstruating women. Estradiol was lower in LPD cycles under either criterion, but LH and FSH were lower only in association with shortened luteal phase (ie, clinical LPD), indicating that clinical and biochemical LPD may reflect different underlying mechanisms. Identifying ovulation in combination with a well-timed luteal progesterone measurement may serve as a cost-effective and specific tool for LPD assessment by clinicians and researchers.
Hormonal contraceptive use and breast cancer in Thai women
Poosari A et al., 2014J Epidemiol
Breast cancer is the most common cancer in women worldwide. We investigated the association of hormonal contraceptive use and breast cancer in Thai women. A cohort study was conducted in Khon Kaen, Thailand. There were 70 cases of histologically confirmed breast cancer among 11 414 women aged 30 to 69 years who were recruited as participants in the cohort study during the period from 1990 through 2001. The study population was followed-up until December 31, 2011. To identify factors associated with incidence of breast cancer, hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a Cox proportional hazards model. The 11 414 women provided a total observation time of 157 200 person-years. Breast cancer risk among women with a history of hormonal contraceptive use was 1.31 times that of women without such a history, but the difference was not statistically significant (95% CI, 0.65-2.65). No type of hormonal contraceptive was associated with a significant increase in breast cancer risk as compared with women who had never used hormonal contraceptives (oral HR = 1.35, 95% CI, 0.65-2.78; HR = 1.25, 95% CI, 0.56-2.80), and there was no relationship between duration of hormonal contraceptive use and breast cancer. There was no association between hormonal contraceptive use and breast cancer; however, this finding should be viewed with caution due to the small number of cases.
Acceptability of prophylactic salpingectomy with delayed oophorectomy as risk-reducing surgery among BRCA mutation carriers
Holman LL et al., 2014Gynecol Oncol
Given the emerging evidence for the fimbria as the site of origin for many serous carcinomas in BRCA mutation carriers, consideration is being given in studying prophylactic salpingectomy with delayed oophorectomy (PSDO) as a risk-reducing surgery. We aimed to determine the interest in a study of PSDO among these women. We evaluated the results of an online survey conducted by Facing Our Risk of Cancer Empowered (FORCE), a patient advocacy group, from October 2010 to August 2012. Premenopausal BRCA mutation carriers with no history of ovarian cancer or prior bilateral salpingo-oophorectomy (BSO) were included. Of the 204 women meeting inclusion criteria, median age was 35 years, 92.5% were white, 25.7% were Jewish, and 16.7% had a history of breast cancer. Overall, 34.3% reported interest in a study of salpingectomy, 35.3% were unsure, and 30.4% were not interested in the study. Women noted the possibility of lowering ovarian cancer risk without menopause as a compelling reason to participate (83.8%). Reasons for not participating in a salpingectomy study included surgical complications (46.6%), potential ovarian damage (42.2%), planning BSO soon (32.4%), and surgical costs (32.8%). Acceptable study risks included the need for two surgeries (77.2%), possibility of not lowering ovarian cancer risk (68%), and disruption of ovarian blood supply (66.5%). One-third of BRCA mutation carriers indicated definite interest in a PSDO study. Potential study risks were acceptable to most women. These findings suggest that patient accrual for a clinical trial of prophylactic salpingectomy with delayed oophorectomy is possible.
Occult microscopic endometriosis: undetectable by laparoscopy in normal peritoneum
Khan KN et al., 2014Human Reproduction
Is there any occurrence of hidden (occult) endometriotic lesions in normal peritoneum of women with and without visible endometriosis? We detected a slightly higher occurrence of occult microscopic endometriosis (OME) in normal peritoneum of women with visible endometriosis than in control women. Based on a small number of cases, the concept of invisible microscopic endometriosis in visually normal peritoneum has been reported for more than a decade but there is controversy regarding their tissue activity and clinical significance. STUDY DESIGN, SIZE, This case-controlled research study was conducted with prospectively collected normal peritoneal samples from 151 women with and 62 women without visible endometriosis. PARTICIPANTS/MATERIALS, SETTING, Normal peritoneal biopsy specimens from different pelvic sites of were collected during laparoscopy. A histological search of all peritoneal biopsy specimens for the detection of invisible endometriosis was done by immunoreaction to Ber-EP4 (epithelial cell marker), CD10 (stromal cell marker) and Calretinin (mesothelial cell marker). Tissue expression of estrogen/progesterone receptors (ER/PR) and cell proliferation marker, Ki-67, was performed by immunohistochemistry to identify tissue activity. MAIN Three different patterns of OME were detected based on (I) the presence of typical gland/stroma, (II) reactive hyperplastic change of endometrioid epithelial cells with surrounding stroma and (III) single-layered epithelium-lined cystic lesions with surrounding stroma. A higher tendency toward the occurrence of OME was found in women with visible endometriosis (15.2%, 23/151) compared with control women (6.4%, 4/62) (P = 0.06, χ(2) test). The epithelial cells and/or stromal cells of OME lesions were immunoreactive to Ber-EP4 and CD10 but not reactive to Calretinin. ER and PR expression was observed in all patterns of OME lesions. Ki-67 index was significantly higher in pattern I/II OME lesions than in pattern III OME lesions (P< 0.05 for each). LIMITATIONS, Bias in the incidence rate of OME lesions in this study cannot be ignored, because we could not analyze biopsy specimens from the Pouch of Douglas of women with revised classification of the American Society of Reproductive Medicine Stage III-IV endometriosis due to the presence of adhesions in the pelvis. We re-confirmed a decade long old concept of invisible (occult) endometriosis in visually normal peritoneum of women with visible endometriosis. The existence of a variable amount of tissue activity in these occult lesions may contribute to the recurrence/occurrence of endometriosis or persistence/recurrence of pain manifestation in women even after successful ablation or excision of visible lesions by laparoscopy. STUDY FUNDING/COMPETING INTEREST(S): This work was supported in part by Grants-in-aid for Scientific Research from the Japan Society for the Promotion of Science. There is no conflict of interest related to this study. Not applicable.
Serum leptin levels and reproductive function during the menstrual cycle
Ahrens K et al., 2014Am J Obstet Gynecol
The purpose of this study was to investigate the role of leptin on reproductive hormones and ovulation. The BioCycle Study (2005-2007) followed 259 healthy premenopausal women not using hormonal contraceptives for ≤2 menstrual cycles (n = 509 cycles). Serum leptin, estradiol, progesterone, luteinizing hormone (LH), follicle-stimulating hormone, and testosterone were measured ≤8 times per cycle. The association of time-varying leptin and reproductive hormones over the cycle was estimated with the use of linear mixed models that were adjusted for percent body fat and age with inverse probability weighting for time-varying physical activity, caloric intake, and other reproductive hormones. The odds ratio for sporadic anovulation (n = 42 cycles) was estimated with the use of generalized linear models that were adjusted for percent body fat and age. Geometric mean serum leptin levels increased from menses to the late luteal phase (16.7-20.4 ng/mL; P < .01), with a mid-cycle peak (21.7 ng/mL) at the time of the LH surge (P < .01). A 10% higher leptin level across the menstrual cycle was associated with higher estradiol levels (2.2%; 95% CI, 1.5-3.0), luteal progesterone levels (2.1%; 95% CI, 0.5-3.7), ovulatory LH levels (1.2%; 95% CI, 0-2.3), testosterone levels (0.6%; 95% CI, 0.3-0.9), and lower follicle-stimulating hormone levels (-0.7%; 95% CI, -1.1 to -0.4). Leptin at the time of the expected LH surge was moderately inversely associated with sporadic anovulation (per log increase in leptin; adjusted odds ratio, 0.58; 95% CI, 0.28-1.22). The association that was observed between leptin level and reproductive function points to a possible relationship between serum leptin level and enhanced fertility.
Relationship between ovarian cysts and infertility: what surgery and when?
Legendre G et al., 2014Fertility and sterility
The relationship between ovarian cysts and infertility is a subject of debate, mainly because it is difficult to determine the real impact of the cyst and its treatment on later fertility. For a long time it was hoped that surgical treatment could prevent potential complications (such as rupture or malignancy). For presumed benign ovarian tumors, fertility sparing should be the main concern. The goal of this survey of current knowledge on the subject is to thoroughly explore the potential relationship between cysts, their treatment, and infertility. Our study is based on a review of the literature dealing with the epidemiology of ovarian cysts and the effects of their surgical management in relation to infertility. Analysis of the epidemiologic data, drawn mainly from comparative studies and cohorts, shows that the role of cysts in infertility is controversial and that the effects of surgical treatment are often more harmful than the cyst itself to the ovarian reserve. Surgery does not seem to improve pregnancy rates. When a surgical option is nonetheless chosen, a conservative laparoscopic approach is more suitable. Besides excision, sclerotherapy and plasma vaporization are promising, offering a greater preservation of the ovarian parenchyma, especially in endometriomas. These techniques must be better defined. The context of the infertility is essential, and surgeons and specialists in reproductive medicine should decide management jointly.
Cardiovascular and general safety of a 24-day regimen of drospirenone-containing combined oral contraceptives: final results from the International Active Surveillance Study of Women Taking Oral Contraceptives
Dinger J et al., 2014Contraception
The "International Active Surveillance Study of Women Taking Oral Contraceptives" investigated the risks of shortand long-term use of an extended 24-day regimen of drospirenone and ethinylestradiol (DRSP24d) compared to established oral contraceptives (OCs) in a routine clinical setting. Prospective, controlled, noninterventional cohort study conducted in the United States and six European countries new users of DRSP24d, DRSP21d (21-day regimens of DRSP-containing OCs), and non-DRSP (OCs without DRSP). All self-reported clinical outcomes of interest (OoI) were validated via attending physicians and relevant source documents. Main OoI were serious clinical outcomes, in particular venous thromboembolism (VTE). Comprehensive follow-up procedures were implemented. Statistical analyses were based on Cox regression models. Primary statistical variable was the VTE hazard ratio (HR) for DRSP24d vs. non-DRSP. A total of 2285 study centers enrolled 85,109 women. Study participants were followed for 2 to 6 years, which generated 206,296 woman-years (WY) of observation. A low loss to follow-up of 3.3% was achieved. DRSP24d, DRSP21d, non-DRSP and levonorgestrel-containing OCs (LNG) showed similar incidence rates of venous and arterial thromboembolism, fatal outcomes, cancer, severe depression and other serious adverse events. VTE incidence rates for DRSP24d, DRSP21d, non-DRSP and LNG were 7.2, 9.4, 9.6 and 9.8 VTE/10,000 WY, respectively. Adjusted HRs for DRSP24d vs. non-DRSP and DRSP24d vs. LNG were 0.8 [95% confidence interval (CI), 0.5-1.3] and 0.8 (95% CI, 0.4-1.5). DRSP24d, DRSP21d, non-DRSP and LNG use was associated with similar risks of serious adverse events, and particularly VTE, during routine clinical use. The 24-day regimen of drospirenone-containing combined OCs is associated with similar risks of venous and arterial thromboembolism, fatal outcomes, cancer, severe depression and other serious adverse events compared to 21-day regimens of drospirenone-containing combined OCs, OCs without drospirenone and LNGs.
Glucocorticoids predict 10-year fragility fracture risk in a population-based ambulatory cohort of men and women: Canadian Multicentre Osteoporosis Study (CaMos)
George Ioannidis et al., 2014Arch Osteoporos
We determined the prospective 10-year association among incident fragility fractures and four glucocorticoid (GC) treatment groups (Never GC, Prior GC, Baseline GC, and Ever GC). Results showed that GC treatment is associated with increased 10-year incident fracture risk in ambulatory men and women across Canada. Using the Canadian Multicentre Osteoporosis Study dataset, we determined the prospective 10-year association between incident fragility fractures and GC treatment. We conducted a 10-year prospective observational cohort study at nine sites across Canada. A total of 9,263 ambulatory men and women 25 years of age and older were included in the analysis. Multivariable Cox proportional hazards analyses were conducted to determine the relationship among GC treatment groups in four levels that included Never GC, Prior GC, Baseline GC, and Ever GC (combined baseline and prior groups) and time to fracture. In each of the Never GC, Prior GC, Baseline GC, and Ever GC treatment groups, the number of participants were 8,832 (95.4 %), 303 (3.3 %), 128 (1.4 %), and 431 (4.7 %), respectively. Of the 9,263 individuals enrolled, incident fragility non-spine, hip, spine, and any fractures were experienced by a total of 896 (9.67 %), 157 (1.69 %), 130 (1.40 %), and 1,102 (11.90 %) over 10-years, respectively. For men and women combined, prior GC treatment was associated with a higher hazard ratio (HR) for time to incident non-vertebral (HR = 1.5, 95 % confidence interval [CI] = 1.1, 2.0), hip (HR = 2.1, 95 % CI = 1.1, 4.0), and any fracture (HR = 1.4, 95 % CI = 1.0, 1.8) compared with never GC treatment. GC treatment is associated with increased 10-year incident fracture risk; this highlights the importance of considering therapy to prevent GC-induced fractures for patients who are using GC for various medical conditions.
Effect of progestins on immunity: medroxyprogesterone but not norethisterone or levonorgestrel suppresses the function of T cells and pDCs
Huijbregts RP et al., 2014Contraception
The potential effect of hormonal contraception on HIV-1 acquisition and transmission represents an important public health issue. Several observational studies have suggested an association between the use of hormonal contraception, in particular injectable depot medroxyprogesterone acetate (DMPA), and an increased risk of HIV-1 acquisition and transmission. We and others have previously demonstrated that DMPA acts as a potent inhibitor of innate and adaptive immune mechanisms. The study presented here addresses the immunomodulatory properties of several common progestins with a potential to replace DMPA. To identify safe alternatives to DMPA, we tested the effect of commonly used progestins on the function of human primary T cells and plasmacytoid dendritic cells (pDCs) obtained from the blood of healthy premenopausal women. Medroxyprogesterone acetate (MPA) inhibited the activation of T cells and pDCs in response to T cell receptorand Toll-like receptor-mediated activation at physiological concentrations. Etonogestrel exerted a partial suppressive activity at high concentrations. In sharp contrast, norethisterone (NET) and levonorgestrel (LNG) did not exhibit detectable immunosuppressive activity. Evidence indicating the immunosuppressive properties of DMPA strongly suggests that DMPA should be discontinued and replaced with other forms of long-term contraception. Since NET and LNG do not exert immunosuppressive properties at physiological concentrations, these progestins should be considered as alternative contraceptives for women at high risk for HIV-1 infection. The presented data suggest that, at physiological levels, the progestins NET and LNG do not suppress cytokine production by immune cells and should be considered as alternatives to DMPA; however, more in vivo testing is needed to confirm this data.
Antidepressant use and 10-year incident fracture risk: the population-based Canadian Multicentre Osteoporosis Study (CaMoS)
C Moura et al., 2014Osteoporos Int
We used data from a large, prospective Canadian cohort to assess the association between selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) and fracture. We found an increased risk of fractures in individuals who used SSRI or SNRI, even after controlling for multiple risk factors. Previous studies have suggested an association between SSRIs and increasing risk of fragility fractures. However, the majority of these studies were not long-term analyses or were performed using administrative data and, thus, could not fully control for potential confounders. We sought to determine whether the use of SSRIs and SNRIs is associated with increased risk of fragility fracture, in adults aged 50 + . We used data from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective randomly selected population-based community cohort; our analyses focused on subjects aged 50+. Time to event methodology was used to assess the association between SSRI/SNRI use, modeled time-dependently, and fragility fracture. Among 6,645 subjects, 192 (2.9%) were using SSRIs or/and SNRIs at baseline. During the 10-year study period, 978 (14.7%) participants experienced at least one fragility fracture. In our main analysis, SSRI/SNRI use was associated with increased risk of fragility fracture (hazard ratio (HR), 1.88; 95% confidence intervals (CI), 1.48-2.39). After controlling for multiple risk factors, including Charlson score, previous falls, and bone mineral density hip and lumbar bone density, the adjusted HR for current SSRI/SNRI use remained elevated (HR, 1.68; 95% CI, 1.32-2.14). Our results lend additional support to an association between SSRI/SNRI use and fragility fractures. Given the high prevalence of antidepressants use, and the impact of fractures on health, our findings may have a significant clinical impact.
The association between endometriosis and chronic endometritis
Takebayashi A et al., 2014PLoS One
To evaluate the association between endometriosis and chronic endometritis. Endometrial specimens were obtained from 71 patients, 34 with endometriosis (endometriosis group) and 37 without endometriosis (non-endometriosis group), who underwent hysterectomy, and the specimens were immunostained for the plasmacyte marker CD138. The rate of chronic endometritis was compared between the endometriosis group and the non-endometriosis group. Furthermore, the 71 patients were also divided into two groups, 28 with chronic endometritis (chronic endometritis group) and 43 without chronic endometritis (non-chronic endometritis group). Logistic regression analysis was performed with variables including age, body mass index (BMI), gravidity and parity, and diagnoses of leiomyoma, adenomyosis, and endometriosis on pathology to examine the independent effect of each variable on chronic endometritis. Patients suffering from cervical invasive carcinoma, endometrial carcinoma, and endometrial polyps or treated with gonadotropin-releasing hormone agonists, progestins, or oral contraceptives before surgery were excluded. Chronic endometritis was identified in 52.94% of the endometriosis group and 27.02% of the non-endometriosis group (p<0.05). Logistic regression analysis revealed that endometriosis was associated with chronic endometritis. This result suggests a strong association between endometriosis and chronic endometritis.
Impact of ART on pregnancies in California: an analysis of maternity outcomes and insights into the added burden of neonatal intensive care
Merritt TA et al., 2014Journal of Perinatology
We reviewed the occurrence of prematurity, low birth weight, multiple gestations, frequency of stillbirths and maternity care-associated variables including hospital stay and hospital charges of women conceiving using assisted reproductive technology (ART) or artificial insemination (AI) compared with women with a history of infertility who conceived naturally, and all other naturally conceived pregnancies in California at non-federal hospitals between 2009 and 2011. At a single center, infants born after ART/AI were compared with infants provided care in the normal nursery. Publically available inpatient data sets from the California Office of Statewide Health Planning and Development for years 2009-2011 using data from all California non-federal hospitals were used to determine the impact of ART on a variety of pregnancy-related outcomes and infant characteristics. Infant data from a single center was used to determine hospital charges for infants delivered over an 18-month period to compare the hospital and physician charges indexed to similar charges for infants admitted to the 'normal' newborn nursery. Among ART/AI pregnancies, there was a 4-5-fold increase in stillbirths, compared with a 2-3-fold increase among women with infertility compared with other naturally conceiving women. ART/AI pregnancies underwent more cesarean sections (fourfold), and a near fourfold increase in the rate of preterm deliveries. Multiple gestations were increased 24-27-fold compared with naturally conceived pregnancies. Maternal hospital stay and hospital charges were increased among those undergoing ART/AI. Infant charges were increased multi-fold for singletons, twins and triplets delivered after ART/AI compared with naturally conceived infants. Multiple births, preterm births and a higher overall rate of fetal anomalies were found in California after ART/AI for 2009-2011. Cesarean section rates, longer length of maternal stay and hospital charges among women receiving ART/AI could be lowered if emphasis on elective single embryo transfers was a higher priority among providers. Charges for the care of infants delivered after ART/AI are substantially higher than among naturally conceived infants born late preterm or at term. Families seeking ART/AI need to be informed of the impact of these adverse pregnancy outcomes, including neonatal outcomes and charges for medical care for their infant(s), when considering ART/AI.
Differential glucocorticoid receptor-mediated effects on immunomodulatory gene expression by progestin contraceptives: implications for HIV-1 pathogenesis
Hapgood JP et al., 2014Am J Reprod Immunol
Whether hormonal contraceptives increase HIV-1 acquisition, transmission and disease progression are critical questions. Clinical research has been hampered by a lack of understanding that different progestins used in contraception exhibit differential off-target effects via steroid receptors other than the progesterone receptor. Of particular, relevance is the relative effects of medroxyprogesterone acetate (MPA) and norethisterone enanthate (NET-EN), widely used as injectable contraceptives in sub-Saharan Africa. While most high-quality clinical studies find no increased risk for HIV-1 acquisition with oral contraception or injectable NET-EN, most do find an increase with MPA, particularly in young women. Furthermore, mounting evidence from animal, ex vivo and biochemical studies are consistent with MPA acting to increase HIV-1 acquisition and pathogenesis, via mechanisms involving glucocorticoid-like effects on gene expression, in particular genes involved in immune function. We report that MPA, unlike NET and progesterone, represses inflammatory genes in human PBMCs in a dose-dependent manner, via the glucocorticoid receptor (GR), at concentrations within the physiologically relevant range. These and published results collectively suggest that the differential GR activity of MPA versus NET may be a mechanism whereby MPA, unlike NET or progesterone, differentially modulates HIV-1 acquisition and pathogenesis in target cells where the GR is the predominant steroid receptor expressed.
Variability in the morphologic assessment of human sperm: use of the strict criteria recommended by the World Health Organization in 2010
Wang Y et al., 2014Fertil Steril
To determine the variability in the recognition of normal sperm and various sperm defects using the strict criteria recommended by the World Health Organization (5th edition, 2010). Sperm morphologic assessment by three experienced evaluators. Image processing laboratory and reproduction research institute. PATIENT(S): Semen donors from a sperm bank. INTERVENTION(S): The morphology of 5,296 sperm was evaluated using statistical analyses of variability. MAIN OUTCOME MEASURE(S): The proportion and coefficients of variation (CVs) of normal sperm, defects of specific parts, and the categories of defects were measured. The degree of agreement between any two of the three evaluators was calculated. The multiple anomalies index, teratozoospermia index, sperm deformity index, and the CVs were also measured. RESULT(S): The CVs of normal sperm, multiple anomalies index, teratozoospermia index, and sperm deformity index were 4.80%, 4.14%, 5.75%, and 6.81%, respectively. A broader range (4.80%-132.97%) of CVs was observed for the recognition of various defects. The coefficients of the degree of agreement concerning specific morphologic parts of sperm varied (0.387-0.607), with lower relative values for the head and mid-piece than for the tail and cytoplasm. CONCLUSION(S): The sperm head is more difficult to evaluate than the other parts using the criteria recommended by the World Health Organization in 2010. The degree of agreement concerning specific parts and various defects varied in broad ranges. A stricter definition for each defect is needed.
The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain
Younger J et al., 2014Clinical Rheumatology
Low-dose naltrexone (LDN) has been demonstrated to reduce symptom severity in conditions such as fibromyalgia, Crohn's disease, multiple sclerosis, and complex regional pain syndrome. We review the evidence that LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells. These effects may be unique to low dosages of naltrexone and appear to be entirely independent from naltrexone's better-known activity on opioid receptors. As a daily oral therapy, LDN is inexpensive and well-tolerated. Despite initial promise of efficacy, the use of LDN for chronic disorders is still highly experimental. Published trials have low sample sizes, and few replications have been performed. We cover the typical usage of LDN in clinical trials, caveats to using the medication, and recommendations for future research and clinical work. LDN may represent one of the first glial cell modulators to be used for the management of chronic pain disorders.
Anti-N-methyl-aspartate receptor encephalitis in identical twin sisters: role for oophorectomy
Masghati S et al., 2014Obstetrics & Gynecology
Anti-N-methyl-aspartate receptor encephalitis is a potentially fatal form of encephalitis and frequently associated with ovarian teratomas. Surgical removal of ovarian teratomas improves clinical outcome, but it is unclear whether bilateral salpingo-oophorectomy for normal-appearing ovaries is of clinical benefit. Our report describes a unique clinical scenario of identical twin sisters with anti-N-methyl-aspartate receptor encephalitis. Neither patient responded to immunosuppressive therapy. Imaging studies showed normal-appearing ovaries. The first twin continued on medical therapy only and died of the disease. The second twin underwent a bilateral salpingo-oophorectomy followed by gradual recovery. Based on our experience in two genetically identical individuals, we suggest considering the removal of normal-appearing ovaries in patients with anti-N-methyl-aspartate receptor encephalitis who fail to respond to medical treatment.
Definition and epidemiology of unexplained infertility
Gelbaya TA et al., 2014Obstetrical & gynecological survey
The diagnosis of unexplained infertility can be made only after excluding common causes of infertility using standard fertility investigations,which include semen analysis, assessment of ovulation, and tubal patency test. These tests have been selected as they have definitive correlation with pregnancy. It is estimated that a standard fertility evaluation will fail to identify an abnormality in approximately 15% to 30% of infertile couples. The reported incidence of such unexplained infertility varies according to the age and selection criteria in the study population. We conducted a review of the literature via MEDLINE. Articles were limited to English-language, human studies published between 1950 and 2013. Since first coined more than 50 years ago, the term unexplained infertility has been a subject of debate. Although additional investigations are reported to explain or define other causes of infertility, these have high false-positive results and therefore cannot be recommended for routine clinical practice. Couples with unexplained infertility might be reassured that even after 12 months of unsuccessful attempts, 50% will conceive in the following 12 months and another 12% in the year after.
The effect of physical activity across the menstrual cycle on reproductive function
Ahrens KA et al., 2014Ann Epidemiol
To evaluate the association between physical activity (PA) across the menstrual cycle and reproductive function. The BioCycle Study (2005-2007) followed 259 healthy premenopausal women not using hormonal contraceptives for up to two menstrual cycles (N = 509 cycles). Serum leptin, estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, and testosterone were measured five to eight times per cycle. Linear mixed models were used to estimate the effect of past-week PA (measured four times during each cycle) on hormone levels. Past-week PA was categorized into tertiles based on metabolic equivalent of task hours per week (cut-points were 15.3 and 35.7). Risk ratios for sporadic anovulation were estimated using generalized linear models. Analyses adjusted for habitual PA (assessed at baseline), body mass index, race, age, and perceived stress. Linear mixed models used inverse probability weights to control for concurrent reproductive hormones and caloric intake. High past-week PA was inversely associated with leptin (-6.6%; 95% confidence interval, -10.6 to -2.5) and luteal phase progesterone (-22.1%; -36.2 to -4.7) as compared with low past-week PA. High past-week PA was not significantly associated with sporadic anovulation (adjusted risk ratio, 1.5; 0.6 to 3.4). High levels of PA were modestly associated with changes in select hormones but not sporadic anovulation among moderate to highly active premenopausal women.
[Interconnection between assisted reproductive technologies, pregnancy complications and risk of birth defects]
Grabar' VV, 2014Georgian medical news
The aim of the article was to investigate the relationship between pregnancy complications, infertility and assisted reproductive technologies (ART). The study was conducted on 1331 couples with complicated reproductive history. It is found that miscarriage and other complications of pregnancy depend rather on the etiopathogenesis of infertility than on the technique of ART. The highest frequency of complications of pregnancy was diagnosed in women with endocrine disorders. In case of congenital malformations in the fetus the frequency of birth defects was 3.6% after in vitro fertilization (IVF) and 1.8% in case of spontaneous pregnancy. It was found an increased risk of birth defects in singleton boys conceived by IVF.
Clitoral vascularization and sexual behavior in young patients treated with drospirenone-ethinyl estradiol or contraceptive vaginal ring: a prospective, randomized, pilot study
Battaglia C et al., 2014The journal of sexual medicine
Oral contraceptives (OC) are effective for birth control and have good cycle control and tolerability. However, the hormonal components could modify mood and libido. The aim of this study is to evaluate the genital vascular effects and sexual behavior of an OC containing 30 μg ethinyl estradiol and 3 mg drospirenone in comparison with a flexible combined contraceptive vaginal ring. Forty women underwent a sonographic assessment of the clitoral anatomy and vascularization and were administered the McCoy Female Sexuality Questionnaire (MFSQ) and the Beck's Depression Inventory questionnaire (BDI). Estradiol, androstenedione, testosterone, and SHBG were assayed. Free Androgen Index (FAI) and Free Estrogen Index (FEI) were calculated. The patients were randomly submitted to OC (group I; n = 21) or vaginal ring (group II; n = 19). Ultrasonographic clitoral volume, pulsatility index (PI) of dorsal clitoral arteries, MFSQ, BDI, and hormonal and biochemical assays were analyzed. After therapy, the testosterone levels were reduced in both groups, whereas estradiol decreased only in group I women. The SHBG increased in all the subjects, and both FAI and FEI decreased. The clitoral volume decreased in all the women. The PI of the dorsal clitoral artery increased only in patients on OC. The hormonal contraception was associated, in both studied groups, with a significant decrease of the two-factor Italian MFSQ score, which was more marked in OC users. In group I subjects, there was a reduction of the number of intercourse/week and a reduction of orgasm frequency during intercourse. The pain during intercourse worsened after OC use. The vaginal ring users reported a vaginal wetness. Six-month treatment with hormonal contraception is associated with a diminished MFSQ score. However, the frequency of sexual intercourse and orgasm was reduced only by the use of OC. The OC use was associated with increased pain during intercourse.
Out-of-pocket fertility patient expense: data from a multicenter prospective infertility cohort
Wu AK et al., 2014The Journal of urology
The high costs of fertility care may deter couples from seeking care. Urologists often are asked about the costs of these treatments. To our knowledge previous studies have not addressed the direct out-of-pocket costs to couples. We characterized these expenses in patients seeking fertility care. Couples were prospectively recruited from 8 community and academic reproductive endocrinology clinics. Each participating couple completed face-to-face or telephone interviews and cost diaries at study enrollment, and 4, 10 and 18 months of care. We determined overall out-of-pocket costs, in addition to relationships between out-of-pocket costs and treatment type, clinical outcomes and socioeconomic characteristics on multivariate linear regression analysis. A total of 332 couples completed cost diaries and had data available on treatment and outcomes. Average age was 36.8 and 35.6 years in men and women, respectively. Of this cohort 19% received noncycle based therapy, 4% used ovulation induction medication only, 22% underwent intrauterine insemination and 55% underwent in vitro fertilization. The median overall out-of-pocket expense was $5,338 (IQR 1,197-19,840). Couples using medication only had the lowest median out-of-pocket expenses at $912 while those using in vitro fertilization had the highest at $19,234. After multivariate adjustment the out-of-pocket expense was not significantly associated with successful pregnancy. On multivariate analysis couples treated with in vitro fertilization spent an average of $15,435 more than those treated with intrauterine insemination. Couples spent about $6,955 for each additional in vitro fertilization cycle. These data provide real-world estimates of out-of-pocket costs, which can be used to help couples plan for expenses that they may incur with treatment.
Combination contraceptives: effects on weight
Gallo MF et al., 2014Cochrane Database Syst Rev
Weight gain is often considered a side effect of combination hormonal contraceptives, and many women and clinicians believe that an association exists. Concern about weight gain can limit the use of this highly effective method of contraception by deterring the initiation of its use and causing early discontinuation among users. However, a causal relationship between combination contraceptives and weight gain has not been established. The aim of the review was to evaluate the potential association between combination contraceptive use and changes in weight. In November 2013, we searched the computerized databases CENTRAL (The Cochrane Library), MEDLINE, POPLINE, EMBASE, and LILACS for studies of combination contraceptives, as well as ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP). For the initial review, we also wrote to known investigators and manufacturers to request information about other published or unpublished trials not discovered in our search. All English-language, randomized controlled trials were eligible if they had at least three treatment cycles and compared a combination contraceptive to a placebo or to a combination contraceptive that differed in drug, dosage, regimen, or study length. All titles and abstracts located in the literature searches were assessed. Data were entered and analyzed with RevMan. A second author verified the data entered. For continuous data, we calculated the mean difference and 95% confidence interval (CI) for the mean change in weight between baseline and post-treatment measurements using a fixed-effect model. For categorical data, such as the proportion of women who gained or lost more than a specified amount of weight, the Peto odds ratio with 95% CI was calculated. We found 49 trials that met our inclusion criteria. The trials included 85 weight change comparisons for 52 distinct contraceptive pairs (or placebos). The four trials with a placebo or no intervention group did not find evidence supporting a causal association between combination oral contraceptives or a combination skin patch and weight change. Most comparisons of different combination contraceptives showed no substantial difference in weight. In addition, discontinuation of combination contraceptives because of weight change did not differ between groups where this was studied. AUTHORS' Available evidence was insufficient to determine the effect of combination contraceptives on weight, but no large effect was evident. Trials to evaluate the link between combination contraceptives and weight change require a placebo or non-hormonal group to control for other factors, including changes in weight over time.
Progesterone therapy, endothelial function and cardiovascular risk factors: a 3-month randomized, placebo-controlled trial in healthy early postmenopausal women
Prior JC et al., 2014PLoS One
Progesterone is effective treatment for hot flushes/night sweats. The cardiovascular effects of progesterone therapy are unknown but evidence suggests that premenopausal normal estradiol with also normal progesterone levels may provide later cardiovascular protection. We compared the effects of progesterone to placebo on endothelial function, weight, blood pressure, metabolism, lipids, inflammation and coagulation. We conducted a randomized, double-blind, 3-month placebo-controlled trial of progesterone (300 mg daily) among 133 healthy postmenopausal women in Vancouver, Canada from 2003-2009. Endothelial function by venous occlusion plethysmography was a planned primary outcome. Enrolled women were 1-11 y since last menstruation, not using hormones (for >6 months), non-smoking, without diabetes, hypertension, heart disease or their medications. Randomized (1∶1) women (55 ± 4 years, body mass index 25 ± 3) initially had normal blood pressure, fasting lipid, glucose and electrocardiogram results. Endothelial function (% forearm blood flow above saline) was not changed with progesterone (487 ± 189%, n = 18) compared with placebo (408 ± 278%, n = 16) (95% CI diff [-74 to 232], P = 0.30). Progesterone (n = 65) and placebo (n = 47) groups had similar changes in systolic and diastolic blood pressure, resting heart rate, weight, body mass index, waist circumference, total cholesterol, low-density lipoprotein cholesterol and triglyceride levels. High-density lipoprotein was lower (-0.14 mmol/L, P = 0.001) on progesterone compared with placebo. Fasting glucose, hs-C-reactive protein, albumin and D-dimer changes were all comparable to placebo. Framingham General Cardiovascular Risk Profile scores were initially low and remained low with progesterone therapy and not statistically different from placebo. Results indicate that progesterone has short-term cardiovascular safety. Endothelial function, weight, blood pressure, waist circumference, inflammation and coagulation were unchanged as were lipids except for HDL-C. The statistically significant decrease in HDL-C levels was not clinically important (based on lack of Cardiovascular Risk Profile change). ClinicalTrials.gov NCT00152438.
Are we overusing IVF?
Kamphuis EI et al., 2014BMJ
The indications for IVF have expanded from tubal disorders to many causes of subfertility, including unexplained. But with limited evidence underpinning its extended remit Esme Kamphuis and colleagues explain how the risks could outweigh the benefits.
Oral contraceptives, hormone replacement therapy and breast cancer risk: a cohort study of 16 928 women 48 years and older
Thorbjarnardottir T et al., 2014Acta Oncol
Findings on potential interactive effects of oral contraceptives (OCs) and hormone replacement therapy (HRT) on breast cancer risk have been inconsistent. We aimed to use population-based cohort data to determine whether former use of OCs affects breast cancer risk among HRT users, taking into account regimens of HRT, duration and currency of use. The cohort consisted of 16 928 Icelandic women who visited the Icelandic Cancer Detection Clinic in 1979-2006 and provided information on use of OCs and HRT when they were 48 years or older. By record linkage to the Icelandic Cancer Registry, all breast cancer diagnosed during follow-up was identified. Using Cox regression, hazard ratios (HRs) for breast cancer according to hormone use were estimated, adjusting for menstrual and reproductive risk factors. Also, interaction analyses were carried out. Breast cancer risk was significantly increased among ever users of combined estrogen and progestin (EP-HRT) preparations (HR=2.61; 95% CI 2.00-3.41) and not among users of estrogen-only regimens (E-only HRT) (HR=1.13; 95% CI 0.85-1.49). Ever users of both OCs and HRT had higher breast cancer risk than users of only one of the two (HR=2.19; 95% CI 1.67-2.87). After restricting the analysis to EP-HRT and focusing on long-term and current use, there was an indication of a negative interaction with ever OC use (p=0.06); HR=2.87; 95% CI 1.79-4.60 for never OC users and HR=2.24; 95% CI 1.51-3.34 for former OC users. After taking HRT regimen, duration and currency of use into account, the results of our population-based cohort study do not support the notion that former OC use increases breast cancer risk among HRT users, on the contrary there was an indication of a slightly lower risk in former OC users, restricted to current, long-term EP-HRT users.
In vitro effects of coital lubricants and synthetic and natural oils on sperm motility
Sandhu RS et al., 2014Fertil Steril
To evaluate the effects of coital lubricants and oils on sperm motility. Comparative prospective in vitro study. University Andrology laboratory. PATIENT(S): Twenty-two normozoospermic donors. INTERVENTION(S): Semen samples were incubated in modified human tubal fluid (mHTF) control and in 10% Pre-Seed, Astroglide, and KY products (Sensitive, Warming, and Tingling) and baby, canola, sesame, and mustard oils. Total and progressive sperm motility was evaluated before and at 5, 30, and 60 minutes of incubation. MAIN OUTCOME MEASURE(S): Sperm motility. RESULT(S): Control samples exhibited no significant decrease in sperm motility. Pre-Seed showed a slight (∼4%) but significant drop in progressive motility after 30 minutes. Total and progressive sperm motility significantly declined under Astroglide, KY products (Sensitive, Warming, and Tingling) and sesame oil incubation. Canola oil significantly decreased total motility after 30 minutes and progressive motility after 5 minutes of incubation. Similarly, baby oil decreased total motility after 60 minutes and progressive motility after 5 minutes. After initial decline, total and progressive sperm motility under Pre-Seed and canola and baby oils remained high. Exposure to mustard oil caused persistent hyperactivation of sperm in each sample with no decrease in motility. CONCLUSION(S): Sesame oil and synthetic coital lubricants impaired sperm motility and may hamper fertility. Pre-Seed and canola, mustard, and baby oils showed no deleterious effect and may be considered sperm-friendly coital lubricants. Mustard oil exposure resulted in hyperactivation of sperm and needs to be studied further.
Timing of oral contraceptive use and the risk of breast cancer in BRCA1 mutation carriers
Kotsopoulos J et al., 2014Breast Cancer Res Treat
It is not clear if early oral contraceptive use increases the risk of breast cancer among young women with a breast cancer susceptibility gene 1 (BRCA1) mutation. Given the benefit of oral contraceptives for the prevention of ovarian cancer, estimating age-specific risk ratios for oral contraceptive use and breast cancer is important. We conducted a case-control study of 2,492 matched pairs of women with a deleterious BRCA1 mutation. Breast cancer cases and unaffected controls were matched on year of birth and country of residence. Detailed information about oral contraceptive use was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the odds ratios (OR) and 95 % confidence intervals (CI) for the association between oral contraceptive and breast cancer, by age at first use and by age at diagnosis. Among BRCA1 mutation carriers, oral contraceptive use was significantly associated with an increased risk of breast cancer for women who started the pill prior to age 20 (OR 1.45; 95 % CI 1.20-1.75; P = 0.0001) and possibly between ages 20 and 25 as well (OR 1.19; 95 % CI 0.99-1.42; P = 0.06). The effect was limited to breast cancers diagnosed before age 40 (OR 1.40; 95 % CI 1.14-1.70; P = 0.001); the risk of early-onset breast cancer increased by 11 % with each additional year of pill use when initiated prior to age 20 (OR 1.11; 95 % CI 1.03-1.20; P = 0.008). There was no observed increase for women diagnosed at or after the age of 40 (OR 0.97; 95 % CI 0.79-1.20; P = 0.81). Oral contraceptive use before age 25 increases the risk of early-onset breast cancer among women with a BRCA1 mutation and the risk increases with duration of use. Caution should be taken when advising women with a BRCA1 mutation to take an oral contraceptive prior to age 25.
The Genetics of Infertility: Current Status of the Field
Zorrilla M et al., 2014Curr Genet Med Rep
Infertility is a relatively common health condition, affecting nearly 7% of all couples. Clinically, it is a highly heterogeneous pathology with a complex etiology that includes environmental and genetic factors. It has been estimated that nearly 50% of infertility cases are due to genetic defects. Hundreds of studies with animal knockout models convincingly showed infertility to be caused by gene defects, single or multiple. However, despite enormous efforts, progress in translating basic research findings into clinical studies has been challenging. The genetic causes remain unexplained for the vast majority of male or female infertility patients. A particular difficulty is the huge number of candidate genes to be studied; there are more than 2,300 genes expressed in the testis alone, and hundreds of those genes influence reproductive function in humans and could contribute to male infertility. At present, there are only a handful of genes or genetic defects that have been shown to cause, or to be strongly associated with, primary infertility. Yet, with completion of the human genome and progress in personalized medicine, the situation is rapidly changing. Indeed, there are 10-15 new gene tests, on average, being added to the clinical genetic testing list annually.
15. The menstrual cycle and lipid levels
Mumford S et al., 2014Handbook of diet and nutrition in the menstrual cycle, periconception and fertility
Pilot test and validation of the peak day method of prospective determination of ovulation against a handheld urine hormone monitor
Porucznik CA et al., 2014BMC Womens Health
Transient exposures may influence fertility and early embryonic development. To assess the time of conception in vivo and conduct concurrent biomonitoring, ovulation must be identified prospectively. We report on the development and validation of a simple, prospective method, the Peak Day method, to determine likely day of ovulation based upon daily observations of cervical fluid. We recruited 98 women to learn the Peak Day method from a brochure, 26 of whom concurrently used the method with blinded daily urine hormone monitoring (estrone glucuronide and luteinizing hormone). All women were instructed to complete an exposure questionnaire immediately upon identifying ovulation. Briefly, the exposure questionnaire captured time-varying and transient exposures such as medication use, water consumption, and amount of sleep. We assessed timely completion of the exposure questionnaire, agreement of women's estimated day of ovulation (EDO) and the EDO by expert review, and agreement between the EDO by expert review and by blinded urine monitoring. Of 147 cycles evaluated, women selected an EDO in 130 (88%) and subsequently completed the periovulatory exposure questionnaire in 122 (94%) cycles. Of the 26 cycles evaluated with blinded hormonal monitoring, the Peak Day "best quality" algorithm, based upon cervical fluid, identified ovulation ± 3 days of the urine monitor in 24 cycles (92%). With simple written instructions, women can identify an estimated day of ovulation and perform periovulatory exposure assessment. The Peak Day method is highly cost-effective and could be applied by researchers to target periconceptional or very early developmental stage exposure assessment.
Stem cell and endometriosis: new knowledge may be producing novel therapies
Yang J et al., 2014International journal of clinical and experimental medicine
The human endometrium is a dynamic tissue, which undergoes cycles of growth and regression with each menstrual cycle. Adult progenitor stem cells are likely responsible for this remarkable regenerative capacity; these same progenitor stem cells may also have an enhanced capacity to generate endometriosis if shed in a retrograde fashion. The progenitor stem cells reside in the uterus, and, however, may also travel from other tissues such as bone marrow to repopulate the progenitor population. Mesenchymal stem cells are also involved in the pathogenesis of endometriosis and may be the principle source of endometriosis outside of the peritoneal cavity when they differentiate into endometriosis in ectopic locations. The present short review mainly summarizes the latest observations contributing to the current knowledge regarding the presence and the potential contribution of stem cells in the etiology of endometriosis. All these data can have clinical implications and provide a basis for new potential therapeutic applications.
412: The effect of very short interpregnancy interval on pregnancy outcomes after previous pregnancy loss
Wong L et al., 2014American Journal of Obstetrics and Gynecology
Beyond labor: the role of natural and synthetic oxytocin in the transition to motherhood
Bell AF et al., 2014Journal of midwifery & women's health
Emerging research raises questions that synthetic oxytocin during childbirth may alter the endogenous oxytocin system and influence maternal stress, mood, and behavior. Endogenous oxytocin is a key component in the transition to motherhood, affecting molecular pathways that buffer stress reactivity, support positive mood, and regulate healthy mothering behaviors (including lactation). Synthetic oxytocin is widely used throughout labor and postpartum care in modern birth. Yet research on the implications beyond labor of maternal exposure to perinatal synthetic oxytocin is rare. In this article, we review oxytocin-related biologic pathways and behaviors associated with the transition to motherhood and evidence supporting the need for further research on potential effects of intrapartum oxytocin beyond labor. We include a primer on oxytocin at the molecular level.
Prevalence of symptoms consistent with a diagnosis of vulvodynia: population-based estimates from 2 geographic regions
Harlow BL et al., 2014American Journal of Obstetrics and Gynecology
We used validated sensitive and specific questions associated with clinically confirmed diagnoses of unexplained vulvar pain (vulvodynia) to compare the cumulative incidence of vulvar pain and prevalence of care-seeking behavior in Boston metropolitan area (BMA) and in Minneapolis/Saint Paul metropolitan area (MSP) from 2001 through 2005 using census-based data, and 2010 through 2012, using outpatient community-clinic data, respectively. We received self-administered questionnaires from 5440 women in BMA and 13,681 in MSP, 18-40 years of age, describing their history of vulvar burning or pain on contact that persisted >3 months that limited/prevented intercourse. By age 40 years, 7-8% in BMA and MSP reported vulvar pain consistent with vulvodynia. Women of Hispanic origin compared to whites were 1.4 times more likely to develop vulvar pain symptoms (95% confidence interval, 1.1-1.8). Many women in MSP (48%) and BMA (30%) never sought treatment, and >50% who sought care with known health care access received no diagnosis. Using identical screening methods, we report high prevalence of vulvar pain in 2 geographic regions, and that access to health care does not increase the likelihood of seeking care for chronic vulvar pain.
Perinatal outcome in singleton pregnancies following in vitro fertilization
Bergh C et al., 2014Seminars in Fetal and Neonatal Medicine
The effect of combined oral contraception on testosterone levels in healthy women: a systematic review and meta-analysis
Zimmerman Y et al., 2014Human reproduction update
BACKGROUND; Combined oral contraceptives (COCs) reduce levels of androgen, especially testosterone (T), by inhibiting ovarian and adrenal androgen synthesis and by increasing levels of sex hormone-binding globulin (SHBG). Although this suppressive effect has been investigated by numerous studies over many years, to our knowledge no systematic review concerning this issue had been performed. This systematic review and meta-analysis was performed to evaluate the effect of COCs on concentrations of total T, free T and SHBG in healthy women and to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T and free T. A review of the literature was performed using database searches (MEDLINE, EMBASE and the Cochrane Central Register of Clinical Trials) and all publications (from inception date until July 2012) investigating the effect of COCs on androgen levels in healthy women were considered eligible for selection. Three reviewers were involved in study selection, data extraction and critical appraisal. For the meta-analysis, data on total T, free T and SHBG were extracted and combined using random effects analysis. Additional subgroup analyses were performed to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T or free T. A total of 151 records were identified by systematic review and 42 studies with a total of 1495 healthy young women (age 18-40 years) were included in the meta-analysis. All included studies were experimental studies and 21 were non-comparative. Pooling of the results derived from all the included papers showed that total T levels significantly decreased during COC use [mean difference (MD) (95% confidence interval, CI) -0.49 nmol/l (-0.55, -0.42); P < 0.001]. Significantly lower levels of free T were also found [relative change (95% CI) 0.39 (0.35, 0.43); P < 0.001], with a mean decrease of 61%. On the contrary, SHBG concentrations significantly increased during all types of COC use [MD (95% CI) 99.08 nmol/l (86.43, 111.73); P < 0.001]. Subgroup analyses revealed that COCs containing 20-25 µg EE had similar effects on total and free T compared with COCs with 30-35 µg EE. In addition, suppressive effects on T levels were not different when comparing different types of progestins. However, subgroup analyses for the estrogen dose and the progestin type in relation to changes in SHBG levels did COCs containing second generation progestins and/or the lower estrogen doses (20-25 µg EE) were found to have less impact on SHBG concentrations. The current literature review and meta-analysis demonstrates that COCs decrease circulating levels of total T and free T and increase SBHG concentrations. Due to the SHBG increase, free T levels decrease twice as much as total T. The estrogen dose and progestin type of the COC do not influence the decline of total and free T, but both affect SHBG. The clinical implications of suppressed androgen levels during COC use remain to be elucidated.
Congenital malformations among babies born following letrozole or clomiphene for infertility treatment
Sharma S et al., 2014PloS one
Clomiphene citrate (CC) is the first line drug for ovulation induction but because of its peripheral antiestrogenic effect, letrozole was introduced as the 2nd line drug. It lacks the peripheral antiestrogenic effect and is associated with similar or even higher pregnancy rates. Since letrozole is a drug for breast cancer, its use for the purpose of ovulation induction became controversial in the light of studies indicating an increased incidence of congenital malformations. To evaluate and compare the incidence of congenital malformations among offsprings of infertile couples who conceived naturally or with clomiphene citrate or letrozole treatment. A retrospective cohort study done at a tertiary infertility centre. A total of 623 children born to infertile women who conceived naturally or following clomiphene citrate or letrozole treatment were included in this study. Subjects were sorted out from medical files of both mother and newborn and follow up study was done based on the information provided by parents through telephonic conversations. Babies with suspected anomaly were called and examined by specialists for the presence of major and minor congenital malformations. Other outcomes like multiple pregnancy rate and birth weight were also studied. Overall, congenital malformations, chromosomal abnormalities were found in 5 out of 171 (2.9%) babies in natural conception group and 5 out of 201 babies in the letrozole group (2.5%) and in 10 of 251 babies in the CC group (3.9%). There was no significant difference in the overall rate of congenital malformations among children born to mothers who conceived naturally or after letrozole or CC treatment. Congenital malformations have been found to be comparable following natural conception, letrozole and clomiphene citrate. Thus, the undue fear against letrozole may be uncalled for.
Exposure to endocrine disrupting chemicals and male reproductive health
Jeng HA, 2014Frontiers in public health
Endocrine disrupting chemicals (EDCs) can interfere with normal hormonal balance and may exert adverse consequences on humans. The male reproductive system may be susceptible to the effects of such environmental toxicants. This review discusses the recent progress in scientific data mainly from epidemiology studies on the associations between EDCs and male reproductive health and our understanding of possible mechanisms associated with the effects of EDCs on male reproductive health. Finally, the review provides recommendations on future research to enhance our understanding of EDCs and male reproductive health. The review highlights the need for (1) well-defined longitudinal epidemiology studies, with appropriately designed exposure assessment to determine potential causal relationships; (2) chemical and biochemical approaches aimed at a better understanding of the mechanism of action of xenoestrogens with regard to low-dose effects, and assessment of identify genetic susceptibility factors associated with the risk of adverse effects following exposure to EDCs.
Use of a mouse in vitro fertilization model to understand the developmental origins of health and disease hypothesis
Feuer SK et al., 2014Endocrinology
1. Endocrinology. 2014 May;155(5):1956-69. 10.1210/en.2013-2081. Epub 2014 Mar 31. Use of a mouse in vitro fertilization model to origins of health and disease hypothesis. Feuer SK(1), Liu X, Donjacour A, Lin W, Simbulan RK, Giritharan G, Piane LD, Kolahi K, Ameri K, Maltepe E, Rinaudo PF. (1)Department of Obstetrics, Gynecology and Reproductive Sciences (S.K.F., X.L., A.D., W.L., R.K.S., G.G., L.D.P., K.K., P.F.R.), (K.A., E.M.), University of California San Francisco, San Francisco, 94143; Nevada Center for Reproductive Medicine (G.G.), Reno, Nevada 89511; Obstetric and Gynecology Department (L.D.P.), University of Turin, Turin, Italy; and Oregon Health & Science University (K.K.), Portland, Oregon 97239. The Developmental Origins of Health and alterations to homeostasis during critical periods individuals to adult-onset chronic diseases syndrome. It remains controversial whether preimplantation embryo manipulation, clinically used to treat patients with infertility, affects long-term growth and metabolism. To address this controversy, assessed the effects of in vitro fertilization (IVF) mice. We demonstrate that IVF and embryo culture, considered optimal for mouse embryo culture, alter postnatal growth trajectory, fat accumulation, and glucose metabolism in adult mice. profiling in serum and microarray analysis of sensitive tissues (liver, skeletal muscle, and adipose tissue) changes in metabolic homeostasis, characterized by mitochondrial dysfunction. Adopting a candidate approach, thioredoxin-interacting protein (TXNIP), a key molecule cellular nutritional and oxidative states with metabolic response, for preimplantation stress and demonstrate transcriptional TXNIP misregulation in selected adult tissues. Importantly, dysregulation of TXNIP expression is associated with enrichment for H4 acetylation at the Txnip promoter that persists through adulthood in adipose tissue. Our data preimplantation embryos to environmental disturbance conception by IVF can reprogram metabolic homeostasis through metabolic, transcriptional, and epigenetic mechanisms with lasting and fitness. This study has wide clinical importance of continued follow-up of IVF-conceived offspring. 10.1210/en.2013-2081 PMC3990843 24684304 [Indexed for MEDLINE]
Adverse Incidents in Fertility Clinics: Lessons to Learn 2013
Human Fertilisation and Embryology Authority, 2014
DIR Jahrbuch 2013 (Deutsches IVF-Register Annual Report 2013)
Deutsches IVF-Register e.V., 2014Deutsches IVF-Register Jahrbuch
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2013. DIR is the German national IVF/ICSI registry, founded 1982 — the oldest continuously operating ART registry. Voluntary professional-society database with high de-facto coverage of German fertility centres. Reports cycles, transfers, pregnancies and clinical outcomes by treatment type (IVF, ICSI, frozen embryo transfer, donor). German-language registry document. Used as a Phase B historical-archive source for the ART Registry Comparison study (cross-registry classification by reporting completeness on 7 framework dimensions).
CARTR Plus 2014 Annual Report (2013 Data) - Canadian Assisted Reproductive Technologies Register Plus
Canadian Fertility and Andrology Society; BORN Ontario, 2014CFAS / BORN Ontario
CARTR Plus annual report covering Canadian ART cycle outcomes; presented at CFAS Annual Meeting October 2015 with 2013 birth outcomes and 2011-2014 cycle data. The Canadian Assisted Reproductive Technologies Register Plus (CARTR Plus) is a voluntary professional society database operated by CFAS in collaboration with BORN Ontario.
Incarcerated Omentum With Tamponade Effect in the Uterine Perforation Scar After Dilation and Curettage: A Case Report
Kim KW, 2014J Med Cases
Perforation of the uterus is the most common immediate complication at the time of dilatation and curettage (D&C). We experienced the case of a patient with intra-abdominal extrusion of fetal part and incarcerated omentum in the perforation site of uterine fundus after D&C. It resulted in massive bleeding after the reduction of the incarcerated omentum which had a tamponade effect. A 26-year-old gravida 2, para 1 woman was referred to our hospital because of uterine perforation during D&C. A laparoscopic exploration was performed. Bleeding started massively at the perforation scar after reduction of the incarcerated omentum which had a tamponade effect. Though bleeding from perforation site stopped after laparoscopic myometrial repair, vaginal bleeding persisted further. The placing of an intrauterine balloon tamponade stopped the vaginal bleeding. The patient recovered successfully and was discharged on the fifth postoperative day. J Med Cases. 2014;5(4):204-207 //dx.doi.org/10.14740/jmc1713w
Chronic Pelvic Pain: An Integrated Approach - APGO Educational Series on Women's Health Issues
Association of Professors in Gynecology and Obstetrics, 2014
Menstrual phase as predictor of outcome after mild traumatic brain injury in women
Wunderle K et al., 2014The Journal of head trauma rehabilitation
To determine whether menstrual cycle phase in women at the time of mild traumatic brain injury (mTBI) predicts 1-month outcomes. Six emergency departments; 5 in Upstate New York, and 1 in Pennsylvania. One hundred forty-four female participants (age, 16-60) who presented to participating emergency departments within 4 hours of mTBI. Nested cohort study with neurologic and quality-of-life outcome assessment, 1 month after enrollment. Female subjects aged 16 to 60 enrolled in the parent cohort study, with 1-month neurological determination data available, were classified into menstrual cycle groups by serum progesterone concentration and self-reported contraceptive use. Rivermead Post Concussion Questionnaire and EuroQoL/EQ5D. Women injured during the luteal phase of their menstrual cycle, when progesterone concentration is high, had significantly lower EuroQoL General Health Ratings and Index Scores than women injured during the follicular phase of their cycle or women taking oral contraceptives. Multivariate analysis confirmed a significant independent effect of menstrual cycle phase on EuroQoL Index Score and the Rivermead Post Concussion Questionnaire Somatic Subscore. Menstrual cycle phase and progesterone concentration at the time of mTBI affect 1-month quality-of-life and neurologic outcomes. This association has important implications for treatment and prognosis after mTBI.