Oral contraceptives and endometriosis: the past use of oral contraceptives for treating severe primary dysmenorrhea is associated with endometriosis, especially deep infiltrating endometriosis

Dominique De Ziegler

Université de Versailles Saint-Quentin-en-Yvelines

Abstract:
BACKGROUND: The relationship between the use of oral contraception (OC) and endometriosis remains controversial. We therefore compared various characteristics of OC use and the surgical diagnosis of endometriosis histologically graded as superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA) or deep infiltrating endometriosis (DIE).

METHODS: This cross-sectional study included 566 patients without visible endometriosis at surgery as controls, and 410 patients with histologically proven endometriosis, categorized by their worst lesions as SUP n = 47, OMA n = 120 and DIE n = 243. Personal data, including on OC use, were prospectively collected during standardized interviews. Statistical analysis was performed using unconditional logistic regression.

RESULTS: Past OC users had an increased incidence of endometriosis (adjusted odd ratios (OR) = 2.79, 95% confidence interval (CI) 1.74-5.12, P = 0.002) of any revised American Fertility Society stage. Women who had previously used OC for severe primary dysmenorrhea were even more frequently diagnosed with endometriosis (adjusted OR = 5.6, 95% CI 3.2-9.8), especially for DIE (adjusted OR = 16.2, 95% CI 7.8-35.3). Women who had previously used OC for other reasons also had an increased risk of endometriosis, but to a lesser extent (adjusted OR = 2.6, 95% CI 1.8-4.1). The age at which OC was initiated, duration of OC use and free interval from last OC use were not significantly different between control and endometriosis women, irrespective of histological grading. Current OC users did not show an increased prevalence of endometriosis (OR = 1.22, 95% CI 0.6-2.52).

CONCLUSIONS: Our data indicate that a history of OC use for severe primary dysmenorrhea is associated with surgical diagnosis of endometriosis, especially DIE, later in life. However, this does not necessarily mean that use of OC increases the risk of developing endometriosis. Past use of OC for primary dysmenorrhea may serve as a marker for women with endometriosis and DIE.


Diagnosis and management of endometrial polyps: a critical review of the  literature

S Salim

University of New South Wales, Randwick, New South Wales, Australia.

Abstract: This review article summarizes the salient literature on the diagnosis and management of endometrial polyps. Electronic resources including Medline, PubMed, CINAHL, The Cochrane Library (including the Cochrane Database of Systematic Reviews), Current Contents, and EMBASE were searched with the MeSH terms including all subheadings and keywords endometrial polyps, abnormal uterine bleeding, polypectomy, polyp management, polyp and diagnosis, and polyp and malignancy. There is a paucity of level I evidence in the literature on the diagnosis and management of this common gynecologic disease. Noninvasive investigations such as transvaginal ultrasonography, with or without the use of 3-dimensional ultrasonography and contrast techniques remain the mainstay of first-line investigation. Hysteroscopic resection is the most effective management for endometrial polyps and allows histologic assessment, whereas blind biopsy or curettage has low diagnostic accuracy and should not be performed. This article will review the cause, epidemiology, clinical presentation, diagnostic investigations, and management of endometrial polyps.

Journal of Minimally Invasive Gynecology


The ethics of uterus transplantation

The ethics of uterus transplantation

Renee Mirkes

Pontifical John Paul II Institute for Studies on Marriage and Family

Abstract: Human uterus transplantation (UTx) is currently under investigation as a treatment for uterine infertility. Without a uterus transplant, the options available to women with uterine infertility are adoption or surrogacy; only the latter has the potential for a genetically related child. UTx will offer recipients the chance of having their own pregnancy. This procedure occurs at the intersection of two ethically contentious areas: assisted reproductive technologies (ART) and organ transplantation. In relation to organ transplantation, UTx lies with composite tissue transplants such as face and limb grafts, and shares some of the ethical concerns raised by these non-life saving procedures. In relation to ART, UTx represents one more avenue by which a woman may seek to meet her reproductive goals, and as with other ART procedures, raises questions about the limits of reproductive autonomy. This paper explores the ethical issues raised by UTx with a focus on the potential gap between women's desires and aspirations about pregnancy and the likely functional outcomes of successful UTx.


Incidence of endometriosis by study population and diagnostic method: the ENDO  study

Germaine M Buck Louis

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Abstract:
Objective: To estimate the incidence of endometriosis in an operative cohort of women seeking clinical care and in a matched population cohort to delineate more fully the scope and magnitude of endometriosis in the context of and beyond clinical care.
Design: Matched-exposure cohort design.
Setting: Surgical centers in the Salt Lake City, Utah, and San Francisco, California, areas. PATIENT(S): The operative cohort comprised 495 women undergoing laparoscopy/laparotomy between 2007 and 2009, and the population cohort comprised 131 women from the surgical centers' catchment areas. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Incidence of endometriosis by diagnostic method in the operative cohort and by pelvic magnetic resonance imaged (MRI) disease in the population cohort. RESULT(S): Endometriosis incidence in the operative cohort ranged by two orders of magnitude by diagnostic method: 0.7% for only histology, 7% for only MRI, and 41% for visualized disease. Endometriosis staging was skewed toward minimal (58%) and mild disease (15%). The incidence of MRI-diagnosed endometriosis was 11% in the population cohort. CONCLUSION(S): Endometriosis incidence is dependent on the diagnostic method and choice of sampling framework. Conservatively, 11% of women have undiagnosed endometriosis at the population level, with implications for the design and interpretation of etiologic research.


O11. Myo-inositol may prevent metabolic and hypertensive disorders in PCOS  pregnant women

Rosario D'Anna

Department of Obstetrics and Gynecology, University of Messina, Italy.


Universal cervical-length screening and vaginal progesterone prevents early preterm births, reduces neonatal morbidity and is cost saving: doing nothing is no longer an option

Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology


Child with Beckwith-Wiedemann syndrome born after assisted reproductive techniques to an human immunodeficiency virus serodiscordant couple

Abstract:
Objective: To report a child with Beckwith-Wiedemann syndrome (BWS) born after assisted reproductive technology (ART) to an HIV serodiscordant couple.

Design: Case report.

Setting: Academic medical center.Patient(s)A child with BWS born after ART to an HIV serodiscordant couple.Intervention(s)Assisted reproductive techniques.Main outcome measure(s)ART and HIV.Result(s)Since 2003, it has been suggested that there is an association between ART and BWS, which is a congenital overgrowth syndrome characterized by macrosomia, macroglossia, visceromegaly, umbilical and abdominal wall abnormalities, and an increased risk of developing embryonal tumors in childhood. It is a multigenic disorder resulting from genetic or epigenetic alterations of genes on chromosome 11p15. Methylation errors account for 50%-60% of sporadic cases and almost 100% of cases born after ART. We report the birth of a child diagnosed with BWS arising from an ART cycle to an HIV serodiscordant couple with no history of infertility. This case cannot constitute conclusive evidence but it raises various questions.Conclusion(s)Assisted reproductive technology seems to be in the causal pathway but a male/female factor or an iatrogenic factor is also possible.


Bioidentical hormone therapy

Bioidentical hormone therapy

Abstract: The change in hormonal milieu associated with perimenopause and menopause can lead to a variety of symptoms that can affect a woman's quality of life. Postmenopausal hormone therapy (HT) is an effective, well-tolerated treatment for these symptoms. However, combined HT consisting of conjugated equine estrogen and medroxyprogesterone acetate has been associated with an increased number of health risks when compared with conjugated equine estrogen alone or placebo. As a result, some women are turning to alternative hormonal formulations known as compounded bioidentical HT because they perceive them to be a safer alternative. This article defines compounded bioidentical HT and explores the similarities and differences between it and US Food and Drug Administration-approved HT. We will examine the major claims made by proponents of compounded bioidentical HT and recommend strategies for management of patients who request bioidentical HT from physicians.


Spine-hip T-score difference predicts major osteoporotic fracture risk independent of FRAX(®): a population-based report from CAMOS

William D Leslie

University of Manitoba, Winnipeg, MB, Canada

Christopher S Kovacs

Memorial University of Newfoundland, St John’s, NL, Canada

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: The WHO fracture risk assessment tool (FRAX(®)) estimates an individual's 10-yr major osteoporotic and hip fracture probabilities. When bone mineral density (BMD) is included in the FRAX calculation, only the femoral neck measurement can be used. Recently, a procedure was reported for adjusting major osteoporotic fracture probability from FRAX with femoral neck BMD based on the difference (offset) between the lumbar spine and the femoral neck T-score values. The objective of the current analysis was to independently evaluate this algorithm in a population-based cohort of 4575 women and 1813 men aged 50 yr and older from the Canadian Multicentre Osteoporosis Study. For women and men combined, there was a 15% (95% confidence interval 7-24%) increase in major osteoporotic fracture risk for each offset T-score after adjusting for FRAX probability calculated with femoral neck BMD. The effect was stronger in women than men, but a significant sex interaction was not detected. Among the full cohort, 5.5% had their risk category reclassified after using the offset adjustment. Sexand age-dependent offsets (equivalent to an offset based on Z-scores) showed improved risk classification among individuals designated to be at moderate risk with the conventional FRAX probability measurement. In summary, the T-score difference between the lumbar spine and femoral neck is an independent risk factor for major osteoporotic fractures that is independent of the FRAX probability calculated with femoral neck BMD.


The Fertile Window and Biomarkers: A Review and Analysis of Normal Ovulation Cycles

Abstract: El objetivo de este artículo es revisar los principales conceptos en la literatura acerca de la ventana de la fertilidad en pacientes con ciclos menstruales normales. El énfasis principal del artículo se ha dirigido al análisis de la teoría de Brown de la ovulación, revisar conceptos básicos de la ovulación, secreción y metabolismo de la hormona folículo estimulante, y al estudio clínico, ecográfico y bioquímicos del desarrollo folicular de la ventana de la fertilidad. Este artículo también repasa los biomarcadores clínicos y los diferentes metabolitos endocrinos que delimitan en la fase fértil del ciclo. Se revisan diferentes estudios en los cuales las valoraciones en suero y orina de los esteroides sexuales, han corroborado tener una correlación directa para enmarcar el período fértil. Actualmente tienen relevancia estos conocimientos en diferentes grupos de interés, sobre todo en mujeres con un alto nivel de motivación interesadas en el reconocimiento de su fertilidad, las cuales pueden beneficiarse mediante la aplicación de conocimientos técnicos actuales que detectan la ventana fértil. También estos conocimientos suelen cobrar importancia en aquellas personas que pertenecen a programas de regulación de la fertilidad (PRF), con intención de distanciar un embarazo, o de reconocer el periodo fértil del ciclo para conseguir un embarazo espontáneamente, o mediante programas de NaProTecnología. Otros grupos de interés, son aquellos en los cuales no se tiene experiencia en cursos de PRF, pero desean mejorar sus conocimientos en el reconocimiento de la fertilidad por medio de una breve entrevista, o por medio de cursos de orientación familiar.


The new women's health science of NaProTECHNOLOGY

Thomas W Hilgers

Pope Paul VI Institute for the Study of Human Reproduction, Omaha, Nebraska.

Abstract: The paper presents the main concepts of NaProTECHNOLOGY. Such problems as family planning effectiveness, targeted hormonal assessment of the menstrual cycle, ovarian hormone and target organ dysfunction, disorders of human ovulation, cooperative progesterone replacement therapy, premenstrual syndrome, postpartum depression, unusual bleeding, infertility and antiadhesion therapy are discussed.


Luteinized unruptured follicle syndrome increased by inactive disease and  selective cyclooxygenase 2 inhibitors in women with inflammatory arthropathies

Mihaela Micu

Spitalul Clinic Județean de Urgență Cluj-Napoca

Romeo Micu

Iuliu Hațieganu University of Medicine and Pharmacy

Abstract:
Objective: Administration of nonsteroidal antiinflammatory drugs (NSAIDs) may impair fertility. The occurrence of the luteinized unruptured follicle (LUF) syndrome was assessed in women with inflammatory arthropathies exposed to NSAIDs and compared to that in nonexposed women.

Methods: Fourteen patients with inflammatory rheumatic disease, 29 women with noninflammatory musculoskeletal conditions, and 449 women not exposed to NSAIDs were studied by intravaginal ultrasound monitoring for follicular development and ovulation in 1 or more menstrual cycles. Disease activity was assessed in inflammatory rheumatic disease.

Results: In 59 monitored cycles of patients with continuous NSAID exposure, 35.6% of LUF syndromes occurred compared to 3.4% of LUF syndromes in untreated women (P < 0.001). Etoricoxib was responsible for 75% of LUF syndromes in patients exposed continuously, whereas diclofenac generated 15% of LUF syndromes. An ibuprofen dosage of 1,600 mg/day did not induce LUF syndrome either at continuous periovulatory or discontinuous exposure. Interestingly, the frequency of LUF syndrome was 46.2% in patients with inactive inflammatory disease compared to 15% in patients with active disease (P = 0.023). Etoricoxib generated LUF syndrome in 94.2% of the cases with inactive disease versus 28.6% in patients with active disease (P = 0.003).

Conclusion: NSAIDs increased the risk of the LUF syndrome, particularly in patients with inactive disease. The selective cyclooxygenase 2 (COX-2) inhibitor etoricoxib was a more potent inductor of LUF syndrome than nonselective COX inhibitors. Continuous periovulatory exposure to NSAIDs should be avoided when planning a pregnancy in patients with rheumatic diseases.


Stress and hormones

Stress and hormones

Abstract: In the modern environment one is exposed to various stressful conditions. Stress can lead to changes in the serum level of many hormones including glucocorticoids, catecholamines, growth hormone and prolactin. Some of these changes are necessary for the fight or flight response to protect oneself. Some of these stressful responses can lead to endocrine disorders like Graves' disease, gonadal dysfunction, psychosexual dwarfism and obesity. Stress can also alter the clinical status of many preexisting endocrine disorders such as precipitation of adrenal crisis and thyroid storm.

Indian Journal of Endocrinology and Metabolism


Role of genetic and environmental factors in British twins with inflammatory  bowel disease

Abstract:
Background: Twin studies provide insight into the complex interaction between genetic and environmental factors in the development of inflammatory bowel disease (IBD). We assessed associations between childhood environmental factors and development of Crohn's disease (CD) and ulcerative colitis (UC) in twins.

Methods: Questionnaires on clinical demographics and exposure to environmental factors were sent to twins with IBD, their healthy co-twins, and their doctors. Kappa statistics were used to examine agreement between twin pairs and odds ratios were calculated by conditional logistic regression.

Results: In all, 250 IBD twin pairs (122 CD; 125 UC; 3 CD/UC; 28 concordant pairs) were analyzed. Concordant monozygotic twins with CD showed good agreement for disease location (κ 0.88; 95% confidence interval [CI]: 0.45-1.00), disease behavior (κ 1.00; 95% CI: 0.43-1.00), and moderate agreement for age at diagnosis and need for medical and surgical therapy. Concordant monozygotic twins with UC showed good agreement for disease extent (κ 0.60; CI 0.13-1.00) and use of thiopurines (κ 0.73; CI 0.10-1.00). In discordant twins, symptomatic childhood mumps infection (odds ratio [OR], 3.8; 95% CI, 1.2-11.3) and oral contraceptives (OR, 4.0; 1.1-14.2) were associated with CD. Smoking was associated with CD (OR, 4.3; 95% CI, 1.9-9.8) but inversely associated with UC (OR, 0.3; 95% CI, 0.1-0.9). Both CD and UC twins had suffered more "gastroenteritis" and spent more time with animals than their co-twins.

Conclusions: Disease phenotype in CD and disease extent in UC appeared to be genetically influenced. Smoking is a risk factor for CD but is protective for UC. Early exposure to "infections" during childhood may be associated with the development of IBD.


Current practice in tubal surgery and adhesion management: a review

A Watrelot

Centre de Recherche en Linguistique Appliquée

Abstract: The diminished role of tubal surgery in infertile women following widespread access to IVF is now being reviewed as more patients and surgeons today consider tubal surgery as an effective alternative to assisted reproduction treatment in certain circumstances. The limitations of and lack of patient acceptance of assisted reproduction treatment for ethical and moral reasons have contributed to this change as well as advances in surgical techniques and instrument technology, notably developments in endoscopic surgery. Strategies in tubal surgery are largely unchanged but the mini-invasive nature of the endoscopic approach has added value because of less tissue trauma, better visualization of the operative field and more rapid healing, which make surgery using today's techniques an integral part of the treatment strategy in infertile couples.


Menarche delay and menstrual irregularities persist in adolescents with type 1 diabetes

Abstract:
BACKGROUND: Menarche delay has been reported in adolescent females with type 1 diabetes (T1DM), perhaps due to poor glycemic control. We sought to compare age at menarche between adolescent females with T1DM and national data, and to identify factors associated with delayed menarche and menstrual irregularity in T1DM.

METHODS: This was a cross-sectional study and females ages 12- 24 years (n = 228) with at least one menstrual period were recruited during their outpatient diabetes clinic appointment. The National Health and Nutrition Examination Survey (NHANES) 2001-2006 data (n = 3690) for females 12-24 years were used as a control group.

RESULTS: Age at menarche was later in adolescent females with T1DM diagnosed prior to menarche (12.81 +/- 0.09 years) (mean+/- SE) (n = 185) than for adolescent females diagnosed after menarche (12.17 0.19 years, p = 0.0015) (n = 43). Average age of menarche in NHANES was 12.27 +/- 0.038 years, which was significantly earlier than adolescent females with T1DM prior to menarche (p < 0.0001) and similar to adolescent females diagnosed after menarche (p = 0.77). Older age at menarche was negatively correlated with BMI z-score (r = -0.23 p = 0.0029) but not hemoglobin A1c (A1c) at menarche (r = 0.01, p = 0.91). Among 181 adolescent females who were at least 2 years post menarche, 63 (35%) reported usually or always irregular cycles.

CONCLUSION: Adolescent females with T1DM had a later onset of menarche than both adolescent females who developed T1DM after menarche and NHANES data. Menarche age was negatively associated with BMI z-score, but not A1c. Despite improved treatment in recent decades, menarche delay and high prevalence of menstrual irregularity is still observed among adolescent females with T1DM.

Reproductive biology and endocrinology : RB&E


Fertility Awareness-Based Methods for Family Planning and as an Alternative to Hormonal Contraceptives for Therapeutic Reasons

Abstract: In current medical practice, many women are prescribed hormonal contraceptives as a method of family planning. Over the years, medical professionals have prescribed hormonal contraceptives to manage numerous health conditions in addition to family planning purposes. A particular question arises in regard to women taking hormonal contraceptives for therapeutic reasons if the drug has a contraceptive effect and abortifacient properties. An important consideration is a definite lack of knowledge among medical professionals and patients about alternatives to hormonal contraceptives. To most lay people and medical professionals, fertility awareness-based methods equate to the outdated calendar rhythm method and therefore tend to be regarded as mostly a matter of chance so that they would have no benefit in helping manage gynecological conditions. In this paper, one will be able to see that modern fertility awareness-based methods are effective as a method of family planning and that there are medical applications that offer an excellent alternative in the treatment of various gynecological conditions, including infertility.


Endocrine modulation of the adolescent brain: a review

Pilar Vigil

Pontificia Universidad Católica de Chile

Abstract: Neurophysiological and behavioral development is particularly complex in adolescence. Youngsters experience strong emotions and impulsivity, reduced self-control, and preference for actions which offer immediate rewards, among other behavioral patterns. Given the growing interest in endocrine effects on adolescent central nervous system development and their implications on later stages of life, this article reviews the effects of gonadal steroid hormones on the adolescent brain. These effects are classified as organizational, the capacity of steroids to determine nervous system structure during development, and activational, the ability of steroids to modify nervous activity to promote certain behaviors. During transition from puberty to adolescence, steroid hormones trigger various organizational phenomena related to structural brain circuit remodelling, determining adult behavioral response to steroids or sensory stimuli. These changes account for most male-female sexual dimorphism. In this stage sex steroids are involved in the main functional mechanisms responsible for organizational changes, namely myelination, neural pruning, apoptosis, and dendritic spine remodelling, activated only during embryonic development and during the transition from puberty to adolescence. This stage becomes a critical organizational window when the appropriately and timely exerted functions of steroid hormones and their interaction with some neurotransmitters on adolescent brain development are fundamental. Thus, understanding the phenomena linking steroid hormones and adolescent brain organization is crucial in the study of teenage behavior and in later assessment and treatment of anxiety, mood disorders, and depression. Adolescent behavior clearly evidences a stage of brain development influenced for the most part by steroid hormones.

Journal of Pediatric and Adolescent Gynecology


Risk of non-fatal venous thromboembolism in women using oral contraceptives  containing drospirenone compared with women using oral contraceptives containing  levonorgestrel: case-control study using United States claims data

Susan S Jick

Boston Collaborative Drug Surveillance Program

Abstract:
Objective: To compare the risk of non-fatal venous thromboembolism in women receiving oral contraceptives containing drospirenone with that in women receiving oral contraceptives containing levonorgestrel.
Design: Nested case-control and cohort study.
Setting: The study was based on information from PharMetrics, a United States based company that collects information on claims paid by managed care plans.

Participants: The study encompassed all women aged 15 to 44 years who received an oral contraceptive containing either drospirenone or levonorgestrel after 1 January 2002. Cases were women with current use of a study oral contraceptive and a diagnosis of venous thromboembolism in the absence of identifiable clinical risk factors (idiopathic venous thromboembolism). Up to four controls were matched to each case by age and calendar time.

MAIN OUTCOME MEASURES: Odds ratios comparing the risk of non-fatal venous thromboembolism in users of the two contraceptives; incidence rates and rate ratios of non-fatal venous thromboembolism for users of each of the study contraceptives.

Results: 186 newly diagnosed, idiopathic cases of venous thromboembolism were identified in the study population and matched with 681 controls. In the case-control analysis, the conditional odds ratio for venous thromboembolism comparing use of oral contraceptives containing drospirenone with use of those containing levonorgestrel was 2.3 (95% confidence interval 1.6 to 3.2). The incidence rates for venous thromboembolism in the study population were 30.8 (95% confidence interval 25.6 to 36.8) per 100,000 woman years among users of oral contraceptives containing drospirenone and 12.5 (9.61 to 15.9) per 100,000 woman years among users of oral contraceptives containing levonorgestrel. The age adjusted incidence rate ratio for venous thromboembolism for current use of oral contraceptives containing drospirenone compared with those containing levonorgestrel was 2.8 (2.1 to 3.8).

Conclusions: The risk of non-fatal venous thromboembolism among users of oral contraceptives containing drospirenone seems to be around twice that of users of oral contraceptives containing levonorgestrel, after the effects of potential confounders and prescribing biases have been taken into account.


Risk of venous thromboembolism in users of oral contraceptives containing  drospirenone or levonorgestrel: nested case-control study based on UK General  Practice Research Database

Abstract:
Objective: To examine the risk of non-fatal idiopathic venous thromboembolism in current users of a combined oral contraceptive containing drospirenone, relative to current users of preparations containing levonorgestrel.
Design: Nested case-control study.
Setting: UK General Practice Research Database.

Participants: Women aged 15-44 years without major risk factors for venous thromboembolism who started a new episode of use of an oral contraceptive containing 30 µg oestrogen in combination with either drospirenone or levonorgestrel between May 2002 and September 2009. Cases were women with a first diagnosis of venous thromboembolism; up to four controls, matched by age, duration of recorded information, and general practice, were randomly selected for each case.

MAIN OUTCOME MEASURES: Odds ratios and 95% confidence intervals estimated with conditional logistic regression; age adjusted incidence rate ratio estimated with Poisson regression.

Results: 61 cases of idiopathic venous thromboembolism and 215 matched controls were identified. In the case-control analysis, current use of the drospirenone contraceptive was associated with a threefold higher risk of non-fatal idiopathic venous thromboembolism compared with levonorgestrel use; the odds ratio adjusted for body mass index was 3.3 (95% confidence interval 1.4 to 7.6). Subanalyses suggested that referral, diagnostic, first time user, duration of use, and switching biases were unlikely explanations for this finding. The crude incidence rate was 23.0 (95% confidence interval 13.4 to 36.9) per 100,000 woman years in current users of drospirenone and 9.1 (6.6 to 12.2) per 100,000 woman years in current users of levonorgestrel oral contraceptives. The age adjusted incidence rate ratio was 2.7 (1.5 to 4.7).

Conclusions: These findings contribute to emerging evidence that the combined oral contraceptive containing drospirenone carries a higher risk of venous thromboembolism than do formulations containing levonorgestrel.


Use of the oral contraceptive pill is associated with increased large artery  stiffness in young women: the ENIGMA study

Abstract:
Background: The oral contraceptive pill (OCP) is widely prescribed throughout the world. Although it is associated with a small but significant increase in blood pressure, the influence of the OCP on large artery stiffness and wave reflection is unclear. The aim of this study was to determine the relationship between use of the OCP and aortic stiffness and wave reflections in a young, healthy cohort of women.

Methods: Participants were drawn from the ENIGMA study, which examines the natural history of blood pressure in young adults. A detailed medical history and lifestyle questionnaire, including OCP details were taken. Blood pressure was measured according to the British Hypertension Society guidelines. Aortic pulse wave velocity (aPWV) was measured together with augmentation index (AIx). Stroke volume (SV) and cardiac output (CO) were also assessed.

Results: Women taking the OCP (n = 225) had a higher SBP and pulse pressure compared with nonusers (n = 660; 112 ± 12 vs. 110 ± 11 and 43 ± 8 vs. 42 ± 8 mmHg, respectively, P < 0.05 for both). CO and SV were also higher (6.6 ± 1.5 vs. 6.3 ± 1.5 l/min, P < 0.01 and 81 ± 16 vs. 78 ± 19 ml, P < 0.05) as was aPWV (5.5 ± 0.7 vs. 5.4 ± 0.7 m/s, P < 0.05). However, there was no difference in DBP (68 ± 9 vs. 69 ± 9 mmHg), mean arterial pressure (81 ± 10 vs. 81 ± 10 mmHg) or AIx (2 ± 12 vs. 3 ± 13%) between the groups.

Conclusion: Use of the OCP is associated with elevated pulse pressure and SV and a small increase in aPWV in young women. The longer term implications of these effects require further investigation.


Pilot evaluation of an internet-based natural family planning education and  service program

Abstract:
Objective: To evaluate the efficacy, knowledge of fertility, and acceptability of a web-based natural family planning (NFP) education and service program.
Design: A 6-month repeated measure longitudinal evaluation pilot study.
Setting: A university based online website.

Participants: The website was piloted with 468 volunteer women seeking NFP services. Of these participants, 222 used the automatic online fertility charting system to avoid pregnancy. The 222 charting participants had a mean age of 29.9 years (SD=5.6), 2.2 children (SD=1.9), 37% were postpartum, and 47% had regular menstrual cycle lengths.

Intervention: Nurse-managed web-based NFP education and service program.

Outcomes: Pregnancies were confirmed by an online self-assessed pregnancy evaluation form. A 10-item fertility quiz and 10-item acceptability survey was administered online.

Results: Among the 222 users avoiding pregnancy, at 6 months of use, there were two correct-use unintended pregnancies that provided a pregnancy rate of 2% and seven total unintended pregnancies providing a typical use pregnancy rate of 7%. Mean knowledge of fertility increased significantly from time of registration (8.96, SD=1.10) to 1 month of use (9.46, SD=.10), t=4.60, p<.001). Acceptability increased nonsignificantly from 1 month of use (45.6; SD=8.98) to 6 months of use (48.4; SD=8.77).

Conclusion: The nurse-managed online NFP system seems to provide adequate knowledge of fertility and help participants meet pregnancy intentions. Acceptability of such a system of NFP is still in question.

Journal of Obstetric, Gynecologic, and Neonatal Nursing : JOGNN


Interstitial cystitis is associated with vulvodynia and sexual dysfunction--a  case-control study

Daniele Porru

Istituti di Ricovero e Cura a Carattere Scientifico

Rossella E Nappi

Department of Obstetrics and Gynecology, Institute for Clinical and Scientific Research (IRCCS) S. Matteo, University of Pavia, Pavia, Italy. renappi@tin.it

Abstract:
Introduction: Dyspareunia and sexual dysfunction are common in women with urological disorders. The study of comorbidity between interstitial cystitis (IC) and vulvodynia seems to be relevant to understand the mechanism generating pain in these conditions.

Aim: To conduct a case-control study for evaluating vulvodynia and sexual dysfunction in women with IC.

Methods: Forty-seven women with new diagnosis (National Institutes of Health [NIH]/National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK] Criteria) of IC were compared with 188 age-matched, negative controls. Each woman completed a semi-structured interview and the Female Sexual Function Index (FSFI). A gynecological examination to assess vulvodynia (cotton swab testing) and genital health (vulvoscopy, Pap smear, culture, and vaginal health index score [VHIS]) was performed.

Main Outcome Measures: Prevalence of vulvodynia, sexual function, and sociodemographic/gynecological variables significantly associated with IC.

Results: Spontaneous or provoked vulvodynia was reported by 23.4% and 74.5% of IC cases, respectively. Sexual function was significantly impaired (median total FSFI score: IC cases 16.85 ± 8.73 vs. controls 27.34 ± 6.41; P<0.0001) in sexually active women, and 23.4% of IC cases as compared to 9% of controls reported no sexual activity in the year preceding the study (χ(2) for trend=38.2, P<0.0001). VHIS was highly impaired in women with IC in comparison with controls (P<0.0001). Variables significantly associated with IC were a diagnosis of menopause (odds ratio [OR]=31.2, 95% confidence interval [CI]=8.1-120.5), past (OR=4.6, 95% CI=1.74-12.1) or current (OR=6.9, 95% CI=2.1-22.1) oral contraceptive use, and a histologically confirmed diagnosis of endometriosis (OR=3.7, 95% CI=1.1-12.7).

Conclusion: We found an increased prevalence of vulvodynia among women with recently diagnosed IC; both conditions seem to have profound consequences on women's sexual function. A potential role for sex hormone-dependent mechanisms into the comorbidity of vulvar and bladder pain is proposed, but further research is warranted.


Effects of hormonal contraceptives on mental rotation and verbal fluency

Abstract: Cognitive abilities, such as verbal fluency and mental rotation, are most sensitive to changes in sex steroids but poorly studied in the context of hormonal contraceptive usage. Therefore, we investigated the performance of mental rotation and verbal fluency in young (21.5±1.8 years) healthy oral contraceptive (OC) users (23 women) and non-users (20 women) during the follicular, ovulatory and luteal phases of the menstrual cycle. Salivary 17β-estradiol, progesterone and testosterone levels were assayed to evaluate hormonal differences between groups and the phases of the menstrual cycle. To assess the effects of progestins having androgenic/anti-androgenic properties, OC users were subdivided into the third and new generation OC users. In addition, positive and negative affects as factors possibly affecting cognitive performance were evaluated. Salivary 17β-estradiol and progesterone levels were significantly lower in hormonal contraception users. Level of salivary testosterone was slightly lower in the OC users group with significant difference only during ovulatory phase. Naturally cycling women performed better on verbal fluency task as compared to OC users. Subjects who used the third generation (androgenic) OCs generated significantly fewer words as compared to new generation (anti-androgenic) OC users and non-users. The third generation OC users demonstrated significantly longer RT in MRT task as compared to non-users. The MRT, verbal fluency and mood parameters did not depend on the phase of menstrual cycle. The parameters of the PANAS (Positive and Negative Affect Schedule) scales did not differ between OC users and non-users. Our findings show that hormonal contraception has an impact on verbal and spatial abilities. Different performances between users of oral contraceptives with androgenic and anti-androgenic properties suggest an essential role for the progestins contained in OCs on cognitive performance.


FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age

Malcolm G Munro

Kaiser Permanente West Los Angeles Medical Center

FIGO Working Group on Menstrual Disorders

Abstract: There is general inconsistency in the nomenclature used to describe abnormal uterine bleeding (AUB), in addition to a plethora of potential causes-several of which may coexist in a given individual. It seems clear that the development of consistent and universally accepted nomenclature is a step toward rectifying this unsatisfactory circumstance. Another requirement is the development of a classification system, on several levels, for the causes of AUB, which can be used by clinicians, investigators, and even patients to facilitate communication, clinical care, and research. This manuscript describes an ongoing process designed to achieve these goals, and presents for consideration the PALM-COEIN (polyp; adenomyosis; leiomyoma; malignancy and hyperplasia; coagulopathy; ovulatory dysfunction; endometrial; iatrogenic; and not yet classified) classification system for AUB, which has been approved by the International Federation of Gynecology and Obstetrics (FIGO) Executive Board as a FIGO classification system.

International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics


Honey: its medicinal property and antibacterial activity

Manisha Deb Mandal

Department of Physiology and Biophysics, KPC Medical College and Hospital, 1F Raja S C Mallick Road, Jadavpur, Kolkata-700 032, India.

Abstract: Indeed, medicinal importance of honey has been documented in the world's oldest medical literatures, and since the ancient times, it has been known to possess antimicrobial property as well as wound-healing activity. The healing property of honey is due to the fact that it offers antibacterial activity, maintains a moist wound condition, and its high viscosity helps to provide a protective barrier to prevent infection. Its immunomodulatory property is relevant to wound repair too. The antimicrobial activity in most honeys is due to the enzymatic production of hydrogen peroxide. However, another kind of honey, called non-peroxide honey (viz., manuka honey), displays significant antibacterial effects even when the hydrogen peroxide activity is blocked. Its mechanism may be related to the low pH level of honey and its high sugar content (high osmolarity) that is enough to hinder the growth of microbes. The medical grade honeys have potent in vitro bactericidal activity against antibiotic-resistant bacteria causing several life-threatening infections to humans. But, there is a large variation in the antimicrobial activity of some natural honeys, which is due to spatial and temporal variation in sources of nectar. Thus, identification and characterization of the active principle(s) may provide valuable information on the quality and possible therapeutic potential of honeys (against several health disorders of humans), and hence we discussed the medicinal property of honeys with emphasis on their antibacterial activities.

Asian Pacific Journal of Tropical Biomedicine


Complete laparoscopic excision of endometriosis in teenagers: is postoperative hormonal suppression necessary?

Ken Sinervo

Center for Endometriosis Care, Atlanta, GA.

Abstract:
OBJECTIVE: To determine long-term outcomes after complete laparoscopic excision done at a tertiary referral center in a teenager population, who were not specifically advised to take postoperative hormonal suppression.

DESIGN: Prospective observational case series (Canadian Task Force II-3).

SETTING: A tertiary referral center that specializes in the laparoscopic treatment of endometriosis.

PATIENT(S): Teenagers with symptoms suspicious for endometriosis who consented and were prospectively recruited to participate in the study.

INTERVENTION(S): All patients underwent diagnostic laparoscopy and complete excision of all areas of abnormal peritoneum with typical and atypical endometriosis. Patients were not specifically advised to take postoperative hormonal suppression.

MAIN OUTCOME MEASURE(S): Rate of recurrent (or persistent) endometriosis.

RESULT(S): Twenty teenagers underwent complete laparoscopic excision of all areas of abnormal peritoneum with typical and atypical endometriosis. Seventeen patients had endometriosis confirmed by histology at initial surgery. Follow-up was up to 66 months (average 23.1 months). There was a statistically significant improvement in most pain symptoms, including bowel-related symptoms, during this time period. The rate of repeat surgery was 8 of 17 patients (47.1%), but the rate of endometriosis (diagnosed visually or histologically) found at surgery was zero. Only one-third of patients took postoperative hormonal suppression for any length of time.

CONCLUSION(S): Complete laparoscopic excision of endometriosis in teenagers--including areas of typical and atypical endometriosis--has the potential to eradicate disease. These results do not depend on postoperative hormonal suppression. These data have important implications in the overall care of teenagers, regarding pain management, but also potentially for fertility. Further large comparative trials are needed to verify these results.


NaProTechnology (Natural Procreative Technology) - A Multifactorial Approach to the Chronic Problem of Infertility

Phil C Boyle

NeoFertility Clinic, Suite 7, 1st Floor, Beacon Mall, Sandyford, Dublin 18, Ireland. Phil.Boyle@NeoFertility.ie.

Abstract:
Description: Infertility is usually a consequence of multiple chronic conditions rather than a single acute condition. We propose that it is erroneous to apply acute medical interventions to a condition that is chronic in nature.
Method: Retrospective analysis of 3 case studies which demonstrate the multifactorial and chronic nature of infertility that were previously managed unsuccessfully with acute intervention using IVF (in Vitro Fertilisation) or ART (Assisted Reproductive Technology).
Results: Demonstration of the multifactorial approach and 3 successful singleton live births using NPT (Natural Procreative Technology or NaProTechnology).

Conclusion: Infertility can be treated successfully with a multifactorial approach which takes into account the chronic nature of infertility and targets treatment to manage multiple factors responsible for the condition.

Discussion: Infertility is not a diagnosis but is often the expression of several underlying ill health conditions which if diagnosed and treated correctly will result in restoration of normal reproductive function. Physicians ought to consider broader diagnostic possibilities in their evaluation of infertile couples. A multifactorial treatment strategy for the chronic condition of infertility may be more effective than the widespread acute strategy employed by ART. Further study is required to investigate this possibility in more detail. Future studies looking at NPT and ART outcomes must be cohort studies comparing populations with similar patient characteristics.

Biomedicina (Sveikatos Mokslai/Health Sciences)


The association between oral contraceptive use, bone mineral density and fractures in women aged 50-80 years

Abstract:
Background: The associations between oral contraceptive (OC) use, bone mineral density (BMD) and the risk of fractures remain controversial.

Study Design: A cross-sectional study of 491 women aged 50-80 years was performed. We assessed OC use and fractures by questionnaire, and BMD and vertebral deformity by dual-energy x-ray absorptiometry.

Results: Ever use of OC was associated with significantly higher BMD at the total body (6%, p<.001) and spine (4%; p=.05) (but not hip) after adjustment for confounders. There was also a significant association between duration of OC use and total body and spine BMD. Use of OCs for 5-10 years was associated with reduced vertebral deformity (adjusted odds ratio 0.46, 95% confidence interval 0.22-0.94).

Conclusions: Oral contraceptive use and duration were associated with higher total body and spine BMD and a consistent reduction in vertebral deformities, although most associations did not reach significance.


Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention

Leo Baggerly

Stacie Nguyen, Leo Baggerly, and Christine French are with GrassrootsHealth, Encinitas, CA. Robert P. Heaney is with Creighton University, Osteoporosis Research Center, Omaha, NE. Edward D. Gorham ...

Abstract:
BACKGROUND: Studies indicate that intake of vitamin D in the range from 1,100 to 4,000 IU/d and a serum 25-hydroxyvitamin D concentration [25(OH)D] from 60-80 ng/ml may be needed to reduce cancer risk. Few community-based studies allow estimation of the dose-response relationship between oral intake of vitamin D and corresponding serum 25(OH)D in the range above 1,000 IU/d.

MATERIALS AND METHODS: A descriptive study of serum 25(OH)D concentration and self-reported vitamin D intake in a community-based cohort (n = 3,667, mean age 51.3 ± 13.4 y).

RESULTS: Serum 25(OH)D rose as a function of self-reported vitamin D supplement ingestion in a curvilinear fashion, with no intakes of 10,000 IU/d or lower producing 25(OH)D values above the lower-bound of the zone of potential toxicity (200 ng/ml). Unsupplemented all-source input was estimated at 3,300 IU/d. The supplemental dose ensuring that 97.5% of this population achieved a serum 25(OH)D of at least 40 ng/ml was 9,600 IU/d.

CONCLUSION: Universal intake of up to 40,000 IU vitamin D per day is unlikely to result in vitamin D toxicity.


Costs of infertility treatment: results from an 18-month prospective cohort study

Abstract: To examine resource use (costs) by women presenting for infertility evaluation and treatment over 18 months, regardless of treatment pursued. Prospective cohort study in which women were followed for 18 months. Setting: eight infertility practices. 398 women recruited from infertility practices. Women completed interviews and questionnaires at baseline and after 4, 10, and 18 months of follow-up; medical records were abstracted after 18 months. Main outcome measures: per-person and per-successful-outcome costs. Treatment groups were defined as highest intensity treatment use. Twenty percent of women did not pursue cycle-based treatment; approximately half pursued IVF. Median per-person costs ranged from $1,182 for medications only to $24,373 and $38,015 for IVF and IVF-donor egg groups, respectively. Estimates of costs of successful outcomes (delivery or ongoing pregnancy by 18 months) were higher ($61,377 for IVF, for example), reflecting treatment success rates. Within the time frame of the study, costs were not significantly different for women whose outcomes were successful and women whose outcomes were not. Although individual patient costs vary, these cost estimates developed from actual patient treatment experiences may provide patients with realistic estimates to consider when initiating infertility treatment.


Acute effects of premenopausal hysterectomy with bilateral oophorectomy on serum lipids, hormonal values, inflammatory markers and metabolism

Christine L Hitchcock

Centre for Menstrual Cycle and Ovulation Research, Division of Endocrinology, University of British Columbia, Vancouver, BC, Canada.

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract:
Objectives: The aim of this study was to provide a clinical reference for the acute postoperative changes to lipids and inflammation following premenopausal hysterectomy with bilateral oophorectomy and compare them to normal reference values.
Design: The study design was a planned secondary analysis of data from a randomized double-blind trial comparing the effectiveness of two different hormone therapies for preventing post-oophorectomy bone loss and controlling vasomotor symptoms. These data were obtained on hospital discharge before randomization to treatment. MATERIALS AND METHODS: Premenopausal women scheduled for a hysterectomy with bilateral oophorectomy for benign reasons were identified from preoperative lists and approached, prior to hospital discharge, to participate in this study. Postoperative data were compared with premenopausal reference intervals using Z scores.

Results: Thirty-three (33) women (mean age 45 ± 4.8 years) were studied an average of 7 days postsurgery. Hemoglobin, albumin, testosterone, and high-density lipoprotein values were decreased in comparison to the normal mean, having Z scores of −3.0, −2.5, −2.4, and −1.7, respectively. C-reactive protein levels were quite significantly elevated (Z score = 20.3).

Conclusions: The high levels of inflammation and abnormal lipids postsurgical menopause are important considerations for physicians when planning subsequent treatment and care. (J GYNECOL SURG 27:9)


Return of ovulation and menses in postpartum nonlactating women: a systematic review

Abstract:
OBJECTIVES: To estimate, from the literature, when nonlactating postpartum women regain fertility.

DATA SOURCES: We searched PubMed and Cochrane Library databases for all articles (in all languages) published in peer-reviewed journals from database inception through May 2010 for evidence related to the return of ovulation and menses in nonlactating postpartum women. Search terms included "Fertility" (Mesh) OR "Ovulation" (Mesh) OR "Ovulation Detection" (Mesh) OR "Ovulation Prediction" (Mesh) OR fertility OR ovulat* AND "Postpartum Period" (Mesh) OR postpartum OR puerperium AND Human AND Female.

METHODS OF STUDY SELECTION: We included articles assessing nonlactating women's first ovulation postpartum. Studies in which women breastfed for any period of time or in whom lactation was suppressed with medications were excluded.

TABULATION, INTEGRATION AND RESULTS: We identified 1,623 articles; six articles reported four studies met our inclusion criteria. In three studies utilizing urinary pregnanediol levels to measure ovulation, mean day of first ovulation ranged from 45 to 94 days postpartum; 20%-71% of first menses were preceded by ovulation and 0%-60% of these ovulations were potentially fertile. In one study that used basal body temperature to measure ovulation, mean first ovulation occurred on day 74 postpartum; 33% of first menses were preceded by ovulation and 70% of these were potentially fertile.

CONCLUSION: Most nonlactating women will not ovulate until 6 weeks postpartum. A small number of women will ovulate earlier, potentially putting them at risk for pregnancy sooner, although the fertility of these early ovulations is not well-established. The potential risk of pregnancy soon after delivery underscores the importance of initiating postpartum contraception in a timely fashion.


Effects of hyperprolactinemia treatment with the dopamine agonist quinagolide on endometriotic lesions in patients with endometriosis-associated hyperprolactinemia

Abstract:
OBJECTIVE: To assess whether dopamine receptor 2 agonists reduced the size of peritoneal lesions in women with endometriosis and elucidate whether affectation of vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2)-dependent angiogenesis was mediating the observed effects.

DESIGN: Proof-of-concept study.

SETTING: University hospital and a university-affiliated private IVF research center.

PATIENT(S): Hyperprolactinemic patients (n = 9) with endometriosis requiring a first surgical intervention (L1) and benefiting from a second-look laparoscopy (L2) were evaluated.

INTERVENTION(S): During L1, four to six peritoneal red lesions were identified. One-half of the lesions were removed and the remaining one-half were labeled with silk knot sutures. After L1, quinagolide was administered in a titrated manner (25-75 μg/d) for 18-20 weeks. During L2, the remaining lesions were surgically excised.

MAIN OUTCOME MEASURE(S): Both L1 and L2 were video recorded to compare the effects of quinagolide treatment on lesion size. Lesions removed at L1 and L2 were compared by means of: 1) histologic analysis; 2) immunohistochemical quantitative analysis of angiogenesis; and 3) quantitative fluorescence polymerase chain reaction array analysis of 84 chemokines and pro-/antiangiogenic molecules.

RESULT(S): Quinagolide induced a 69.5% reduction in the size of the lesions, with 35% vanishing completely. Histologic analysis showed tissue degeneration, which was supported by down-regulation of VEGF/VEGFR2, three proangiogenic cytokines (CCL2, RUNX1, and AGGF1) and plasminogen activator inhibitor (PAI) 1, a potent inhibitor of fibrinolysis in the L2 lesions.

CONCLUSION(S): By interfering with angiogenesis, enhancing fibrinolysis, and reducing inflammation, quinagolide reduces or eliminates peritoneal endometriotic lesions in women with endometriosis.


Folic acid food fortification-its history, effect, concerns, and future directions

Abstract: Periconceptional intake of folic acid is known to reduce a woman's risk of having an infant affected by a neural tube birth defect (NTD). National programs to mandate fortification of food with folic acid have reduced the prevalence of NTDs worldwide. Uncertainty surrounding possible unintended consequences has led to concerns about higher folic acid intake and food fortification programs. This uncertainty emphasizes the need to continually monitor fortification programs for accurate measures of their effect and the ability to address concerns as they arise. This review highlights the history, effect, concerns, and future directions of folic acid food fortification programs.


Reproductive history and oral contraceptive use in relation to risk of  triple-negative breast cancer

Lucile L Adams-Campbell

Slone Epidemiology Center at Boston University, Boston, Massachusetts and 2Lombardi Comprehensive Cancer Center at Georgetown University Medical Center, Washington, District of Columbia

Anne McTiernan

University at Buffalo, State University of New York

Jean Wactawski-Wende

Department of Epidemiology and Environmental Health, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY.

Abstract:
Background: Triple-negative (ie, estrogen receptor [ER], progesterone receptor, and HER2 negative) breast cancer occurs disproportionately among African American women compared with white women and is associated with a worse prognosis than ER-positive (ER+) breast cancer. Hormonally mediated risk factors may be differentially related to risk of triple-negative and ER+ breast cancers.

Methods: Using data from 155,723 women enrolled in the Women's Health Initiative, we assessed associations between reproductive and menstrual history, breastfeeding, oral contraceptive use, and subtype-specific breast cancer risk. We used Cox regression to evaluate associations with triple-negative (N = 307) and ER+ (N = 2610) breast cancers and used partial likelihood methods to test for differences in subtype-specific hazard ratios (HRs).

Results: Reproductive history was differentially associated with risk of triple-negative and ER+ breast cancers. Nulliparity was associated with decreased risk of triple-negative breast cancer (HR = 0.61, 95% confidence interval [CI] = 0.37 to 0.97) but increased risk of ER+ breast cancer (HR = 1.35, 95% CI = 1.20 to 1.52). Age-adjusted absolute rates of triple-negative breast cancer were 2.71 and 1.54 per 10,000 person-years in parous and nulliparous women, respectively; by comparison, rates of ER+ breast cancer were 21.10 and 28.16 per 10,000 person-years in the same two groups. Among parous women, the number of births was positively associated with risk of triple-negative disease (HR for three births or more vs one birth = 1.46, 95% CI = 0.82 to 2.63) and inversely associated with risk of ER+ disease (HR = 0.88, 95% CI = 0.74 to 1.04). Ages at menarche and menopause were modestly associated with risk of ER+ but not triple-negative breast cancer; breastfeeding and oral contraceptive use were not associated with either subtype.

Conclusion: The association between parity and breast cancer risk differs appreciably for ER+ and triple-negative breast cancers. These findings require further confirmation because the biological mechanisms underlying these differences are uncertain.

Journal of the National Cancer Institute


Providing hospice in the womb

Providing hospice in the womb

Abstract: Amy Kuebelbeck was 25 weeks into her pregnancy when she received the terrible news. Her fetus had been diagnosed with an incurable heart defect. If she carried through with her pregnancy, her baby's life would be a brief one. Kuebelbeck did continue her pregnancy and gave birth to a boy. Her new

CMAJ : Canadian Medical Association Journal = Journal De l'Association Medicale  Canadienne


Emotional distress in infertile women and failure of assisted reproductive technologies: meta-analysis of prospective psychosocial studies

Abstract: OBJECTIVE: To examine whether pretreatment emotional distress in women is associated with achievement of pregnancy after a cycle of assisted reproductive technology. DESIGN: Meta-analysis of prospective psychosocial studies. DATA SOURCES: PubMed, Medline, Embase, PsycINFO, PsychNET, ISI Web of Knowledge, and ISI Web of Science were searched for articles published from 1985 to March 2010 (inclusive). We also undertook a hand search of reference lists and contacted 29 authors. Eligible studies were prospective studies reporting a test of the association between pretreatment emotional distress (anxiety or depression) and pregnancy in women undergoing a single cycle of assisted reproductive technology. Review methods Two authors independently assessed the studies for eligibility and quality (using criteria adapted from the Newcastle-Ottawa quality scale) and extracted data. Authors contributed additional data not included in original publication. RESULTS: Fourteen studies with 3583 infertile women undergoing a cycle of fertility treatment were included in the meta-analysis. The effect size used was the standardised mean difference (adjusted for small sample size) in pretreatment anxiety or depression (priority on anxiety where both measured) between women who achieved a pregnancy (defined as a positive pregnancy test, positive fetal heart scan, or live birth) and those who did not. Pretreatment emotional distress was not associated with treatment outcome after a cycle of assisted reproductive technology (standardised mean difference -0.04, 95% confidence interval -0.11 to 0.03 (fixed effects model); heterogeneity I2=14%, P=0.30). Subgroup analyses according to previous experience of assisted reproductive technology, composition of the not pregnant group, and timing of the emotional assessment were not significant. The effect size did not vary according to study quality, but a significant subgroup analysis on timing of the pregnancy test, a contour enhanced funnel plot, and Egger's test indicated the presence of moderate publication bias. CONCLUSIONS: The findings of this meta-analysis should reassure women and doctors that emotional distress caused by fertility problems or other life events co-occurring with treatment will not compromise the chance of becoming pregnant.


Urine bisphenol-A (BPA) level in relation to semen quality

Abstract:
OBJECTIVE: To determine whether urine bisphenol-A (BPA) levels are associated with lower semen quality.

DESIGN: Cohort study.

SETTING: Four regions in China where high exposure to BPA in the workplace existed.

PATIENT(S): 218 men with and without BPA exposure in the workplace.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): Semen parameters.

RESULT(S): After adjustment for potential confounders using linear regression, increasing urine BPA level was statistically significantly associated with [1] decreased sperm concentration, [2] decreased total sperm count, [3] decreased sperm vitality, and [4] decreased sperm motility. Compared with men who did not have detectable urine BPA levels, those with detectable urine BPA had more than three times the risk of lowered sperm concentration and lower sperm vitality, more than four times the risk of lower sperm count, and more than twice the risk of lower sperm motility. The urine BPA level was not associated with semen volume or abnormal sperm morphology. Similar dose-response associations were observed among men with environmental BPA exposure at levels comparable with those in the U.S population. Despite a markedly reduced sample size, the inverse correlation between increased urine BPA levels and decreased sperm concentration and total sperm count remained statistically significant.

CONCLUSION(S): These results provide the first epidemiologic evidence of an adverse effect of BPA on semen quality.


Effect of omega-3 polyunsaturated fatty acid supplementation on semen profile and enzymatic anti-oxidant capacity of seminal plasma in infertile men with idiopathic oligoasthenoteratospermia: a double-blind, placebo-controlled, randomised study

Abstract: Effective medical treatments of infertile men with idiopathic oligoasthenoteratospermia (OAT) have yet to be determined. This study considered two major aims: (i) to measure the changes in semen parameters, omega-3 fatty acids (FA) compositions and anti-oxidant activity; (ii) to determine if the administration of omega-3 FA affect semen quality in infertile men with OAT. Two hundred thirty-eight infertile men with idiopathic OAT were randomised to eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), 1.84 g per day (EPAX 5500TG; Lysaker, Norway), or placebo for 32 weeks. The semen parameters were assessed according to WHO criteria, and the EPA and DHA concentrations were determined in red blood cells (RBCs), seminal plasma and sperm cells at baseline and 32-week treatment period. Of randomised subjects, 211 (88.7%) completed the full 32-week randomisation period. The anti-oxidant status of seminal plasma was also evaluated by measuring the superoxide dismutase (SOD) and catalase-like activity. In the total group of participants, all EPA and DHA levels in RBC, and seminal plasma, were statistically significantly correlated with those in spermatozoa (both P = 0.001). A significant improvement of sperm cell total count (from 38.7 ± 8.7 ' 10⁶ to 61.7 ± 11.2 ' 10⁶, P = 0.001) and sperm cell concentration (from 15.6 ± 4.1 ' 10⁶ per ml to 28.7 ± 4.4 ' 10⁶ per ml, P = 0.001) was observed in the omega-3 group. A significant positive correlation was found between the EPA and DHA in seminal plasma and the semen parameters. Seminal plasma EPA and DHA concentrations were positively correlated with seminal plasma SOD-like and catalase-like activity (both P = 0.001). In seminal plasma, both SOD-like and catalase-like activity were positively correlated with sperm count, sperm motility, and sperm morphology. Oligoasthenoteratospermic men with low levels of EPA and DHA may benefit from omega-3 FA supplementation. Further studies are warranted to shed more light on this important issue.


Is the oral contraceptive pill associated with fracture in later life? New evidence from the Royal College of General Practitioners Oral Contraception Study

Abstract:
Background: Several studies, including an earlier analysis from the Royal College of General Practitioners (RCGP) Oral Contraception Study, have suggested that ever users of oral contraceptives have an increased risk of fracture when compared with never users. In this paper, we examined a subset of women in the RCGP study living in Scotland to determine whether this risk has persisted.

Study Design: A nested case-control study was carried out using data collected prospectively for the RCGP Oral Contraception Study. Cases were women with a first ever diagnosis of fracture (n=651), age-matched to two controls (n=1302). Adjustments were made for smoking, social class and parity.

Results: There was not a significant association between ever use of oral contraception and fracture (adjusted odds ratio 1.05, 95% confidence interval 0.86-1.29), compared with never users. Neither were significant associations found between fracture and smoking, social class and parity. The findings did not vary materially with age or type of fracture.

Conclusion: Ever use of oral contraception was not associated with fracture in this study.


Characteristics of the menstrual cycle after discontinuation of oral contraceptives

Abstract:
BACKGROUND: Menstrual cycle function may continue to be altered after discontinuation of oral contraceptives (OC). Few studies have been published on the effects of recent OC use on menstrual cycle parameters; none have examined characteristics of the menstrual flow or the quality of cervical mucus. The purpose of this retrospective matched cohort study is to assess biomarkers of the menstrual cycle after discontinuation of OCs.

METHODS: Among a sample of women who daily recorded observations of menstrual cycle biomarkers, 70 women who had recently discontinued OCs were randomly matched by age and parity with 70 women who had not used OCs for at least 1 year. Outcomes investigated included overall cycle length, length of the luteal phase, estimated day of ovulation, duration of menstrual flow, menstrual intensity, and mucus score. Differences between recent OC users and controls were assessed using random effects modeling.

RESULTS: Recent OC users had statistically significantly lower scores for mucus quality for cycles 1 and 2. Additionally, OC users had a later estimated day of ovulation that was statistically significant in cycle 2 and a decreased intensity of menstrual flow that was significant in the first four cycles (difference = -0.48 days). In random effects modeling, all these parameters were significantly different for the first six cycles combined.

CONCLUSIONS: Menstrual cycle biomarkers are altered for at least two cycles after discontinuation of OCs, and this may help explain the temporary decrease in fecundity associated with recent OC use.


Progesterone for Symptomatic Perimenopause Treatment - Progesterone politics,  physiology and potential for perimenopause

Abstract: Perimenopause, women's normal midlife reproductive transition, is highly symptomatic for about 20% of women who are currently inaccurately counseled and inappropriately treated with oral contraceptives, menopausal hormone therapy or hysterectomy. About 80% of perimenopausal women experience vasomotor symptoms (VMS), 25% have menorrhagia, and about 10% experience mastalgia. The majority of women describe varying intensities of sleep, -coping or mood difficulties. Women are more symptomatic because common knowledge inaccurately says that estradiol (E2) levels are dropping/deficient. Evidence shows that with disturbed brain-ovary feedbacks, E2 levels average 26% higher and soar erratically - some women describe feeling pregnant! Also, ovulation and progesterone (P4) levels become insufficient or absent. The most symptomatic women have higher E2 and lower P4 levels. Because P4 and E2 complement/counterbalance each other's tissue effects, oral micronized P4 (OMP4 300 mg at -bedtime) is a physiological therapy for treatment-seeking, symptomatic perimenopausal women. Given cyclically (cycle d 14-27, or 14 on/off) in menstruating midlife women, OMP4 decreases cyclic VMS, improves sleep and premenstrual mastalgia. Menorrhagia is treated with ibuprofen 200mg/6h plus OMP4 cycle d 4-28. For insulin resistance, metformin plus cyclic or daily OMP4 decreases insulin resistance and weight gain. Non-responsive migraines need daily OMP4 plus usual therapies. VMS and insomnia in late perimenopause respond to daily OMP4. In summary, OMP4 is a physiology-based therapy that improves sleep, treats VMS, does not increase breast proliferation or cancer risk, increases bone formation and has beneficial cardiovascular effects. A


Modulation of spermatozoon acrosome reaction

Renán F Orellana

Pontificia Universidad Católica de Chile

Abstract: Spermatozoon acrosome reaction is an exocytotic event of the utmost importance for the development of mammalian fertilisation. Current evidence shows that the triggering of the acrosome reaction (AR) could be regulated by the action of diverse compounds, namely, metabolites, neurotransmitters and hormones. The aim of the present review is to describe the modulating effects of several compounds that have been classified as inductors or inhibitors of acrosome reaction. Among AR inductors, it is necessary to mention progesterone, angiotensin II, atrial natriuretic peptide, cathecolamines, insulin, leptin, relaxin and other hormones. Regarding the inhibitors, oestradiol and epidermal growth factor are among the substances that retard AR. It is worth mentioning that gamma-aminobutyric acid, a neurotransmitter known to be an inhibitor in the central nervous system, has been shown to induce AR. The multiple hormones located in the fluids of the female reproductive tract are also likely to act as subtle regulators of AR, constituting a fundamental aspect for the development of successful fertilisation. Finally, it is necessary to emphasise that the study of regulation exerted by hormones and other compounds on AR is essential for further understanding of mammalian reproductive biology, especially spermatozoon physiology.


Birth Defects in Singleton versus Multiple ART Births in Japan (2004–2008)

Abstract: The purpose of the present study was to evaluate the relative risk (RR) of multiple births for birth defects after assisted reproductive technology (ART) using Japanese nationwide data from 2004 to 2008 with singletons as the reference group. In multiples compared to singletons, the percentage of birth defects per pregnancy were significantly higher (RR = 1.88, 95% confidence interval (CI) 1.60-2.13), the percentage of birth defects per live birth was not significantly higher (RR = 0.90, 95% CI 0.78-1.05 or RR = 0.94, 95% CI 0.81-1.10), and the early neonatal mortality rate was significantly higher (RR = 2.68, 95% CI 1.52-4.70 or RR = 2.80, 95% CI 1.60-4.92). The early neonatal mortality per 10,000 live births was slightly higher in ART (5.09) than in the general population (3.86). We concluded that the impact of birth defects after ART would be larger in families with multiples compared to families with singletons, since the mean number of children would be larger in the former.


Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries

World Endometriosis Research Foundation Global Study of Women's Health consortium

Lone Hummelshoj

World Endometriosis Research Foundation, London, United Kingdom.


The endocrinology of perimenopause: need for a paradigm shift

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Christine L Hitchcock

Centre for Menstrual Cycle and Ovulation Research, Division of Endocrinology, University of British Columbia, Vancouver, BC, Canada.

Abstract: Perimenopause, rather than a time of declining estrogen, is characterized by three major hormonal changes that may begin in regularly menstruating women in their mid-thirties: erratically higher estradiol levels, decreased progesterone levels (in normally ovulatory, short luteal phase or anovulatory cycles), and disturbed ovarian-pituitary-hypothalamic feedback relationships. Recent data show that approximately a third of all perimenopausal cycles have a major surge in estradiol occurring de novo during the luteal phase. This phenomenon, named "luteal out of phase (LOOP)" event, may explain a large proportion of symptoms and signs for symptomatic perimenopausal women. Large urinary hormone data-sets from women studied yearly over a number of years in the Study of Women Across the Nation (SWAN) and in the Tremin data will eventually provide a more clear prospective understanding of within-woman hormonal changes. Predicting menopause proximity with FSH or Inhibin B levels is documented to be ineffective. Anti-Mullerian hormone levels may prove predictive. Finally, there is an urgent need to change perimenopause understandings, language and therapies used for midlife women's symptoms to reflect these hormonal changes.


Naprotechnology for Women's Health: Promising Results from Clinical Trials

Thomas W Hilgers

Pope Paul VI Institute for the Study of Human Reproduction, Omaha, Nebraska.

Abstract: The paper presents the main concepts of NaProTECHNOLOGY. Such problems as family planning effectiveness, targeted hormonal assessment of the menstrual cycle, ovarian hormone and target organ dysfucntion, disorders of human ovulation, cooperative progesterone replacement therapy, premustrual syndrome, postpartum depression, unusual bleeding, infertility and antiadhesion therapy are discussed.


Can anti-ovarian antibody testing be useful in an IVF-ET clinic?

Abstract:
OBJECTIVE: To establish importance of anti-ovarian antibodies (AOA) testing in infertile women.

DESIGN: A clinical reproductive outcome comparative study between two groups of women undergoing IVF-ET. Group 1 consists of women tested positive for AOA, put on corticosteroid therapy, reverted to AOA negative and then taken up for IVF-ET. Group 2 were seronegative for AOA.

SETTING: Major urban infertility reference centre and National research institute.

PATIENT(S): Five hundred seventy infertile women enrolled for IVF-ET.

INTERVENTION(S): AOA testing, corticosteroid therapy and IVF-ET/ICSI.

MAIN OUTCOME MEASURE(S): Comparable clinical outcome and significance of AOA testing established.

RESULTS: AOA positive serum samples were sent periodically to re-investigate presence of AOA after corticosteroid therapy and women turned AOA negative were taken up for IVF-ET. Of the 70/138 women in group 1 who were treated with corticosteroids and turned seronegative for AOA, 22/70 were poor responders and needed donor oocyte-recipient cycles. Results demonstrated that fertilization and clinical pregnancy rates between both groups are comparable. Nevertheless, it is also observed that there is poor response to stimulation protocol, smaller number of oocytes retrieved and more spontaneous abortions in group 1 women. Hence not all outcomes following the treatment are comparable between the two groups. Usefulness of the test was established in two case studies.

CONCLUSIONS: AOA testing could be included in the battery of tests investigating and treating infertility.

Journal of assisted reproduction and genetics


The NaPro Technology Revolution: Unleashing the Power in a Woman's Cycle

Abstract: Dr. Thomas W. Hilgers draws on decades of medical experience to provide educational and revolutionary insights into the world of women's health. The NaPro Technology Revolution provides real solutions to real problems such as infertility, repetitive miscarriage, menstrual cramps, postpartum depression, PMS, prematurity prevention, ovarian cysts, hormonal abnormalities, irregular/abnormal bleeding, chronic discharges, polycystic ovarian disease, and family planning. Hilgers sheds light on abnormal ovarian function, an issue that millions of women unknowingly suffer from. His methods have proven to assist infertile couples nearly three times more successfully than those who use In Vitro Fertilization, without the dangers of early abortions, frozen embryos, or high rates of multiple pregnancy. The NaProTechnology Prematurity Prevention Program cuts the rate from the national 12.7% to 7%. The NaPro Technology Revolution discusses what every woman has a right to know about her body, her health, and her future!


Cell phones and male infertility: a review of recent innovations in technology and consequences

Abstract: Cell phones have become a vital part of everyday life. However, the health risks associated with their usage are often overlooked. Recently, evidence from several studies supports a growing claim that cell phone usage may have a detrimental effect on sperm parameters leading to decreased male fertility. Nonetheless, other studies showed no conclusive link between male infertility and cell phone usage. The ambiguity of such results is attributed to the lack of a centralized assay for measuring inflicted damage caused by cell phones. Study design, ethics, and reproducibility are all aspects which must be standardized before any conclusions can be made.

International braz j urol : official journal of the Brazilian Society of Urology


CARTR 2011 Annual Report - 2010 Results from the Canadian ART Register

Abstract: Canadian ART Register (CARTR) annual report for 2010. A total of 18,454 cycles was reported to CARTR. Voluntary professional society database operated by the Canadian Fertility and Andrology Society.


DIR Jahrbuch 2010 (Deutsches IVF-Register Annual Report 2010)

Abstract: Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2010. 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).


Abstract: 10.1016/j.fertnstert.2011.03.058. Epub 2011 May 4. International Committee for Monitoring Assisted Reproductive Technology (ICMART) world report: assisted reproductive technology 2003. Nygren KG(1), Sullivan E, Zegers-Hochschild F, Mansour R, Ishihara O, Adamson GD, de Mouzon J. (1)IVF Unit, Queen Sophia Hospital, Stockholm, Sweden. OBJECTIVE: To analyze information on assisted reproductive technologies (ART) performed globally. DESIGN: Data on access, efficacy, and safety of ART were collected for the year 2003 from 54 countries. SETTING: National and regional ART registries globally. PATIENT(S): Patients undergoing ART globally. INTERVENTION(S): Collection and analysis of international ART registry data. MAIN OUTCOME MEASURE(S): Number of cycles performed in reporting countries and regions globally for different ART procedures with resulting pregnancy, live birth and multiple birth rates. RESULT(S): A total of 433,427 initiated cycles reported in this registry resulted in 173,424 babies born. This corresponded to a delivery rate per aspiration of 22.4% for in vitro fertilization (IVF), 23.3% for intracytoplasmic sperm injection (ICSI), and a delivery rate per transfer of 17.1% for frozen embryo transfer. Although there is wide variation among countries and regions, the overall proportion of deliveries with twins and triplets from IVF and ICSI was 24.8% and 2.0%, respectively. There were wide variations in access, and compared with the previous report (year 2002), there was a 3.9% increase in the number of reported cycles and a minor increase in the delivery rate per aspiration. There was also a marginal decline in the mean number of embryos transferred and in the rate of multiple births. CONCLUSION(S): ART access, efficacy, and safety varies greatly globally. Collection and analysis of data over time will benefit ART patients, providers, and policy makers. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.


Bone changes and fracture related to menstrual cycles and ovulation

Abstract: Women's menstrual cycles and bone remodeling are linked in part by their co-dependency on the stressand resource-associated variables that govern both of their cyclical natures. Therefore, it is not surprising that evolution has resulted in the same signaling molecules and pathways that regulate normal ovarian function to be involved in bone remodeling and turnover. This review will first provide an overview of the normal menstrual cycle, its modification by age and ovulatory disturbances, and how it parallels bone remodeling. Epidemiological and clinical evidence will be presented that link bone remodeling, strength, and fractures with women's history of reproductive and menstrual cycle characteristics. This combined evidence will then be presented alongside a synthesis of current concepts derived from basic science investigations focused on understanding the molecular mechanisms underlying the influence of ovarian factors on bone physiology. Osteoporosis is a significant source of morbidity for older women. The data presented in this review suggest that a woman's reproductive cycle and ovulatory characteristics foreshadow the future health of her bones. More importantly, identifying the key mechanisms underlying reproductive and bone health would not only provide essential preventative strategies, but may also uncover attractive targets for the treatment of osteoporosis.

Critical Reviews in Eukaryotic Gene Expression


Independent external validation of nomograms for predicting risk of low-trauma fracture and hip fracture

Christopher S Kovacs

Memorial University of Newfoundland, St John’s, NL, Canada

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

the Canadian Multicentre Osteoporosis Study Research Group

Jacqueline R Center

Faculty of MedicineUniversity of New South WalesSydneyAustralia

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Abstract:
Background: A set of nomograms based on the Dubbo Osteoporosis Epidemiology Study predicts the fiveand ten-year absolute risk of fracture using age, bone mineral density and history of falls and low-trauma fracture. We assessed the discrimination and calibration of these nomograms among participants in the Canadian Multicentre Osteoporosis Study.

Methods: We included participants aged 55-95 years for whom bone mineral density measurement data and at least one year of follow-up data were available. Self-reported incident fractures were identified by yearly postal questionnaire or interview (years 3, 5 and 10). We included low-trauma fractures before year 10, except those of the skull, face, hands, ankles and feet. We used a Cox proportional hazards model.

Results: Among 4152 women, there were 583 fractures, with a mean follow-up time of 8.6 years. Among 1606 men, there were 116 fractures, with a mean follow-up time of 8.3 years. Increasing age, lower bone mineral density, prior fracture and prior falls were associated with increased risk of fracture. For low-trauma fractures, the concordance between predicted risk and fracture events (Harrell C) was 0.69 among women and 0.70 among men. For hip fractures, the concordance was 0.80 among women and 0.85 among men. The observed fracture risk was similar to the predicted risk in all quintiles of risk except the highest quintile of women, where it was lower. The net reclassification index (19.2%, 95% confidence interval [CI] 6.3% to 32.2%), favours the Dubbo nomogram over the current Canadian guidelines for men.

Interpretation: The published nomograms provide good fracture-risk discrimination in a representative sample of the Canadian population.


Fracture prediction and calibration of a Canadian FRAX® tool: a population-based report from CaMos

LA Fraser, L Langsetmo, C Berger, G Ioannidis, D Goltzman, J D Adachi, A Papaioannou, R Josse, C S Kovacs, W P Olszynski, T Towheed, D A Hanley, S M Kaiser, J Prior, S Jamal, N Kreiger, J P Brown, H Johansson, A Oden, E McCloskey, J A Kanis, W D Leslie

Abstract:
A new Canadian WHO fracture risk assessment (FRAX®) tool to predict 10-year fracture probability was compared with observed 10-year fracture outcomes in a large Canadian population-based study (CaMos). The Canadian FRAX tool showed good calibration and discrimination for both hip and major osteoporotic fractures.
Introduction: The purpose of this study was to validate a new Canadian WHO fracture risk assessment (FRAX®) tool in a prospective, population-based cohort, the Canadian Multicentre Osteoporosis Study (CaMos).

Methods: A FRAX tool calibrated to the Canadian population was developed by the WHO Collaborating Centre for Metabolic Bone Diseases using national hip fracture and mortality data. Ten-year FRAX probabilities with and without bone mineral density (BMD) were derived for CaMos women (N = 4,778) and men (N = 1,919) and compared with observed fracture outcomes to 10 years (Kaplan-Meier method). Cox proportional hazard models were used to investigate the contribution of individual FRAX variables.

Results: Mean overall 10-year FRAX probability with BMD for major osteoporotic fractures was not significantly different from the observed value in men [predicted 5.4% vs. observed 6.4% (95%CI 5.2-7.5%)] and only slightly lower in women [predicted 10.8% vs. observed 12.0% (95%CI 11.0-12.9%)]. FRAX was well calibrated for hip fracture assessment in women [predicted 2.7% vs. observed 2.7% (95%CI 2.2-3.2%)] but underestimated risk in men [predicted 1.3% vs. observed 2.4% (95%CI 1.7-3.1%)]. FRAX with BMD showed better fracture discrimination than FRAX without BMD or BMD alone. Age, body mass index, prior fragility fracture and femoral neck BMD were significant independent predictors of major osteoporotic fractures; sex, age, prior fragility fracture and femoral neck BMD were significant independent predictors of hip fractures.

Conclusion: The Canadian FRAX tool provides predictions consistent with observed fracture rates in Canadian women and men, thereby providing a valuable tool for Canadian clinicians assessing patients at risk of fracture.


Risk of congenital heart defects associated with assisted reproductive technologies: a population-based evaluation

Abstract:
Aims: To estimate the risk of congenital heart defects (CHD) associated with assisted reproductive technologies (ART).Methods and resultsWe used data from the Paris Registry of Congenital Malformations on 5493 cases of CHD and 3847 malformed controls for which no associations with ART were reported in the literature. Assisted reproductive technologies included inductors of ovulation only, in vitro fertilization, and intracytoplasmic sperm injection. Exposure to ART was higher for cases than controls (4.7 vs. 3.6%, P= 0.008) and was associated with a 40% increase in the maternal age, socioeconomic factors, and year of birth-adjusted odds of CHD without chromosomal abnormalities [adjusted odds ratio (OR) 1.4, 95% confidence interval (CI) 1.1-1.7]. Assisted reproductive technologies were specifically associated with significant increases in the odds of malformations of the outflow tracts and ventriculoarterial connections (adjusted OR 1.7, 95% CI 1.2-2.4) and of cardiac neural crest defects and double outlet right ventricle (adjusted OR 1.7, 95% CI 1.1-2.7). In general, we found specific associations between methods of ART and subcategories of CHD.

Conclusion: Cases with CHD were more likely to have been conceived following ART when compared with malformed controls. This higher risk for CHD varied specifically according to the method of ART and the type of CHD and may be due to ART per se and/or the underlying infertility of couples.


Evaluating the effect of magnesium and magnesium plus vitamin B6 supplement on the severity of premenstrual syndrome

Abstract:
BACKGROUND: Since premenstrual syndrome (PMS) can cause suicide, dissociation of familial relationships, abnormalities in the daily work and inter-personal relationships in the patients, and bring about direct and indirect economic burden for the society, it is important to resolve the problems of the patients. The objective of the current study is to determine the effect of magnesium (Mg), combination of vitamin B6 and Mg, and the placebo on the severity of PMS in the patients affected by the disease referred to the health centers of Isfahan University of Medical Sciences during 2009-2010.

METHODS: The participants were randomly assigned to two intervention groups and one control group. The study was carried out for four months in ten selected health centers in Isfahan. To confirm the PMS diagnosis in patients, they were asked to fill out the PMS daily symptom record form for two months and then, when the diagnosis was confirmed, the participants were randomly assigned to one of the three groups of the study (Mg, Mg plus vitamin B6, and placebo). Medical intervention was carried out in two menstrual cycles and the results of pre- and post-test were compared.

RESULTS: After the intervention, the mean score of PMS significantly decreased in all the three groups (p < 0.05). The decrease was the greatest in the Mg plus vitamin B6 group, and was the least in the placebo group.

CONCLUSIONS: The findings indicated that Mg plus vitamin B6 and placebo has the greatest and the least effect on the mean score of PMS, respectively.

Iranian journal of nursing and midwifery research


Pregnancy outcome at extremely advanced maternal age

Abstract:
OBJECTIVE: The purpose of this study was to evaluate pregnancy outcome in women at extremely advanced maternal age (≥ 45 years).

STUDY DESIGN: We compared the condition of women aged ≥ 45 years (n = 177) in a 10:1 ratio (20-29, 30-39, and 40-44 years.). Subgroup analysis compared the condition of women aged 45-49 years with those women aged ≥ 50 years.

RESULTS: The rates of gestational diabetes mellitus and hypertensive complications were higher for the study group, compared with the whole group (17.0% vs 5.6% and 19.7% vs 4.5%, respectively; P < .001), as was the rate of preterm delivery at <37 and <34 weeks of gestation (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.6 and OR, 3.5; 95% CI, 1.4-9.0, respectively). The rates of cesarean delivery (OR, 31.8; 95% CI, 18.0-56.1), placenta previa, postpartum hemorrhage, and adverse neonatal outcome were significantly higher among the study group. The risk for gestational diabetes mellitus, preeclampsia toxemia, preterm delivery, and neonatal intensive care unit admission was increased for women aged ≥ 50 years.

CONCLUSION: Pregnancy at extreme advanced maternal age is associated with increased maternal and fetal risk.

American journal of obstetrics and gynecology


Insulin resistance/hyperinsulinemia and reproductive disorders in infertile women

Abstract: Obesity, which disturbs lipid and glucose metabolism, is a recent medical concern. It threatens human health and also has adverse effects on reproductive functions by causing insulin resistance/hyperinsulinemia, especially in women with polycystic ovary syndrome (PCOS). For PCOS patients to prevent these adverse effects, it is important to take into account improving their lifestyles by exercise and proper diets. The relationship between insulin resistance/hyperinsulinemia and reproductive disorders should be understood as fully as possible in order to provide effective treatment. It is well known that insulin resistance and compensatory hyperinsulinemia can be triggered by obesity with visceral fat accumulation. Hyperinsulinemia affects granulosa cells in small follicles and theca cells. This condition induces early response to luteinizing hormones on granulosa cells of small follicles and causes premature differentiation of these cells, which eventually results in anovulation. For improvement of anovulation because of hyperinsulinemia, insulin-sensitizing agents (biguanide and thiazolidinedione derivatives) are useful. Hyperinsulinemia may adversely affect the endometrial functions and environment, and evoke implantation disturbance. Treatment with an insulin-sensitizing agent (metformin) improves the levels of glycodelin, insulin-like growth factor binding protein 1, and blood flow in spiral arteries during the peri-implantation period. It supports endometrial function, improves the endometrial environment, and facilitates embryo implantation. The rate of early pregnancy loss during the first trimester is 30-50% in women with PCOS, which is threefold higher than for normal women. Metformin treatment improves the levels of insulin, the homeostasis model assessment for insulin resistance, and plasminogen activator inhibitor activity, and decreases early pregnancy loss. It goes without saying that lifestyle change is fundamental for improving reproductive performance in addition to treatment with insulin-sensitizing agents.


Effectiveness of delayed-release doxylamine and pyridoxine for nausea and vomiting of pregnancy: a randomized placebo controlled trial

Abstract:
OBJECTIVE: To evaluate the effectiveness of Diclectin (doxylamine succinate 10 mg-pyridoxine hydrochloride 10 mg, delayed-release preparation) as compared with placebo for nausea and vomiting of pregnancy.

STUDY DESIGN: A randomized, double-blind, multicenter placebo controlled trial studying pregnant women suffering from nausea and vomiting of pregnancy, analyzed by intention to treat. Women received Diclectin (n = 131) or placebo (n = 125) for 14 days. Nausea and vomiting of pregnancy symptoms were evaluated daily using the pregnancy unique quantification of emesis scale.

RESULTS: Diclectin use resulted in a significantly larger improvement in symptoms of nausea and vomiting of pregnancy compared with placebo based on both the pregnancy unique quantification of emesis score (-4.8 ± 2.7 vs -3.9 ± 2.6; P = .006) and quality of life. After the trial, 64 (48.9%) women receiving Diclectin asked to continue compassionate use of their medication, as compared with 41 (32.8%) of placebo-treated women (P = .009).

CONCLUSION: Diclectin delayed release formulation of doxylamine succinate and pyridoxine hydrochloride is effective and well tolerated in treating nausea and vomiting of pregnancy.


Longitudinal study of insulin resistance and sex hormones over the menstrual cycle: the BioCycle Study

Edwina H Yeung

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Lihui Chen

Fujian Agriculture and Forestry University

Richard W Browne

University at Buffalo, State University of New York

Jean Wactawski-Wende

Department of Epidemiology and Environmental Health, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY.

Abstract:
CONTEXT: Conflicting findings have been reported regarding the effect of menstrual cycle phase and sex hormones on insulin sensitivity.

OBJECTIVE: The aim was to determine the pattern of insulin resistance over the menstrual cycle and whether variations in sex hormones explain these patterns.

DESIGN: The BioCycle study is a longitudinal study that measured hormones at different phases of the menstrual cycle. Participants had up to eight visits per cycle; each visit was timed using fertility monitors to capture sensitive windows of hormonal changes.

SETTING: The study was conducted in the general community of the University at Buffalo (Buffalo, NY).

PARTICIPANTS: A total of 257 healthy, premenopausal women (age, 27±8 yr; body mass index, 24±4 kg/m2) participated in the study.

MAIN OUTCOME MEASURES: We measured fasting insulin, glucose, and insulin resistance by the homeostasis model of insulin resistance (HOMA-IR).

RESULTS: Significant changes in HOMA-IR were observed over the menstrual cycle; from a midfollicular phase level of 1.35, levels rose to 1.59 during the early luteal phase and decreased to 1.55 in the late-luteal phase. HOMA-IR levels primarily reflected changes in insulin and not glucose. After adjustment for age, race, cycle, and other sex hormones, HOMA-IR was positively associated with estradiol (β=0.082; P<0.001) and progesterone (β=0.025; P<0.001), and inversely associated with FSH (adjusted β=-0.040; P<0.001) and SHBG (β=-0.085; P<0.001). LH was not associated with HOMA-IR. Further adjustment for BMI weakened the association with SHBG (β=-0.057; P=0.06) but did not affect other associations.

CONCLUSION: Insulin exhibited minor menstrual cycle variability. Estradiol and progesterone were positively associated with insulin resistance and should be considered in studies of insulin resistance among premenopausal women.

The Journal of clinical endocrinology and metabolism


Laparo-endoscopic single site hysterectomy in gynecologic surgery

Abstract: Laparo-endoscopic single site (LESS) surgery has recently gained broader acceptance as a less-invasive approach to traditional multi-port laparoscopic procedures. LESS hysterectomy represents the gynecologic surgeon's progression toward this goal of performing minimally invasive hysterectomy procedures through increasingly fewer incisions. Although this procedure offers improved cosmesis and potentially decreased post-operative pain, there are also many challenges to adoption of this surgical procedure. LESS hysterectomy is associated with a steep learning curve and the need for the gynecologic surgeon to adopt new technologies and develop a new set of surgical skills. Following the basic principles of LESS surgery is essential for the gynecologic surgeon to safely and efficiently adopt this surgical procedure. Advances in surgical instrumentation will continue to allow surgeons to perform increasingly complex LESS surgical procedures in the future.