Multi-decade summary report covering assisted reproductive technology (ART) cycles performed in Japan from 1992 through 2014, published by the Ethics Committee of the Japan Society of Obstetrics and Gynecology (JSOG). Provides longitudinal trends in cycle volume, treatment-type stratification, and outcomes from JSOG-registered ART facilities.
The topic of how the menstrual cycle is a vital sign which could signal pathophysiologic process has received considerable attention in the past decade. The current recommendations of various academic groups will be discussed as well as the FertilityTMM Care method of charting and the Naprotechnology approach to evaluating abnormalities of the menstrual cycle. Two clinical scenarios seen in adolescent medicine, PCOS and AUB, will be analyzed looking at the pathophysiology of these clinical scenarios and their management. The approach will be one that conducts an evaluation to try to find the underlying problem and aims to restore the normal physiology of the menstrual cycle.
The American Academy of Pediatrics, the American College of Obstetrics and Gynecology and the New York Academy of Sciences have published academic statements during the past ten years emphasizing the need for providers to teach patients how to chart and the important clinical ramifications of using this charting as a vital sign. In 2006 the American Academy of Pediatrics published in the Pediatrics Journal a "Menstruation Using the Menstrual Sign as a Vital Sign." In 2015, the American College of Obstetrics and Gynecology published a Committee Opinion emphasizing the need to teach women the charting of their menses and the important pathophysiologic process that could be detected with the charting.
Dotters-Katz SK et al., 2017·Obstetrics and gynecology
To identify risk factors for maternal morbidity after previable prelabor rupture of membranes (PROM). We conducted a case-control study of singleton and twin pregnancies complicated by previable PROM (14.0-22.9 weeks of gestation) at a single tertiary care referral institution, 2000-2015. Pregnancies complicated by fetal anomalies, previable PROM within 2 weeks of chorionic villus sampling or amniocentesis, and those with contraindications to expectant management (eg, chorioamnionitis) were excluded. Cases were women with the primary outcome of composite maternal morbidity (defined as having at sepsis, intensive care unit admission, acute renal insufficiency, uterine curettage, hysterectomy, deep vein thrombosis, pulmonary embolus, blood transfusion, readmission, or maternal death). Controls were women without the primary composite morbidity. Bivariate analysis compared demographic, clinical, and management characteristics of women in the case group and those in the control group. Multivariable logistic regression models were developed to quantify the association between maternal characteristics and composite severe maternal morbidity. During the study period, 174 women presented with by previable PROM and were candidates for expectant management. Sixty-five (37%) women opted for immediate delivery; 109 (63%) elected expectant management. Twenty-five of 174 (14%) experienced one or more components of the composite maternal morbidity (cases) and were compared with 149 (86%) women in the control group. Women in the case group were more not more likely to elect expectant management (68% compared with 59%, P=.40), but were more likely to be aged 35 years or older (40% compared with 14%, P=.002) or to be carrying twins (52% compared with 16%, P<.01). In the regression model, twin gestation and age 35 years or older were both significantly associated with increased odds of composite maternal morbidity (odds ratio [OR] 5.62, 95% confidence interval [CI] 2.21-14.3 and OR 4.00, 95% CI 1.48-10.8, respectively). Antenatal counseling of women with previable PROM should include that one in seven women experience significant morbidity. Although expectant management was not associated with increased risk in this cohort, women with twins or those aged 35 years or older were at substantially increased risk.
Chronic pelvic pain is prevalent in 2% of women population globally. The etiology is multifactorial. Even in the absence of pelvic pathology, there is a subgroup of women who do not respond to analgesic and anti-inflammatory therapy. Chronic pelvic pain can be inhibited by direct inhibition of impulses in the preganglionic afferent neuron by closing the hypothetical gate in the dorsal horn of the spinal cord. Transcutaneous electrical nerve stimulation (TENS) is based on the gate control theory of abolishing the painful stimuli by providing simultaneous inputs in larger myelinated nerve fibers. This study was designed to assess the effectiveness and safety of TENS in idiopathic chronic pelvic pain. It is a prospective, experimental study to evaluate the effectiveness of TENS versus placebo in reducing pain severity in chronic pelvic pain (G1 = 30, G2 = 32, G3 = 30, and G0 = 30). Patients with chronic pelvic pain due to benign lesions of genital tract, gastrointestinal, and renal disorders were excluded from the study after performing an ultrasound study of abdomen and pelvis. Ten treatment sessions (5 sessions/week) of 30 min were conducted. There was a significant improvement in pain scores in TENS group as compared with control group, and two patients were completely pain free following TENS therapy. In women patients with idiopathic chronic pelvic pain, TENS can be a useful intervention. TENS units are safe, economical, and easily commercially available.
1. Biomedicines. 2017 Apr 18;5(2):16. 10.3390/biomedicines5020016. Reduced Pro-Inflammatory Cytokines after Eight Weeks Fibromyalgia. Parkitny L(1), Younger J(2). (1)Department of Psychology, University of Alabama at Birmingham, Birmingham, AL
35205, USA. lukeparkitny@interleuk.in.
(2)Department of Psychology, University of Alabama at Birmingham, Birmingham, AL
35205, USA. younger@uab.edu. Fibromyalgia (FM) is a complex, multi-symptom affects women. The majority of those affected are symptomatic control from the few treatments that are approved for FM. 10-week, single-blind, crossover trial we tested weeks of oral administration of low-dose naltrexone (LDN). women with an average age of 46 years, symptom severity of 62 out of 100, symptom duration of 14 years. We found that LDN plasma concentrations of interleukin (IL)-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6,
IL-10, IL-12p40, IL-12p70, IL-15, IL-17A, IL-27, interferon (IFN)-α,
transforming growth factor (TGF)-α, TGF-β, tumor necrosis factor (TNF)-α, granulocyte-colony stimulating factor (G-CSF). We also found a 15% FM-associated pain and an 18% reduction in overall symptoms. this pilot trial suggest that LDN treatment in fibromyalgia reduction of several key pro-inflammatory cytokines and symptoms. role of LDN as an atypical anti-inflammatory further. 10.3390/biomedicines5020016
PMC5489802
28536359 The authors declare no conflict of interest.
This population-based cohort study examined preconception TSH levels and their association with pregnancy outcomes in 184,611 Chinese women planning to conceive. Women were classified into reference (0.48-2.49 mIU/L), upper limit (2.5-4.28 mIU/L), and high TSH (4.29-10 mIU/L) groups. The high normal TSH group showed higher rates of spontaneous abortion, preterm birth, and operative vaginal delivery compared to reference. The high TSH group had higher rates of spontaneous abortion, stillbirth, and preterm births.
Sunderam S et al., 2017·Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)
Assisted Reproductive Technology Surveillance - United States, 2014. Sunderam S(1), Kissin DM(1), Crawford SB(1), Folger SG(1), Jamieson DJ(1), Warner L(1), Barfield WD(1). (1)Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, CDC. Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Women who undergo ART procedures are more likely than women who conceive naturally to deliver multiple-birth infants. Multiple births pose substantial risks to both mothers and infants, including obstetric complications, preterm delivery, and low birthweight infants. This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2014 and compares birth outcomes that occurred in 2014 (resulting from ART procedures performed in 2013 and 2014) with outcomes for all infants born in the United States in 2014. 2014. In 1996, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102-493). Data are collected through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC. This report includes data from 52 reporting areas (the 50 states, the District of Columbia, and Puerto Rico). In 2014, a total of 169,568 ART procedures (range: 124 in Wyoming to 21,018 in California) with the intent to transfer at least one embryo were performed in 458 U.S. fertility clinics and reported to CDC. These procedures resulted in 56,028 live-birth deliveries (range: 52 in Wyoming to 7,230 in California) and 68,782 infants born (range: 64 in Wyoming to 8,793 in California). Nationally, the total number of ART procedures performed per million women of reproductive age (15-44 years), a proxy measure of the ART usage rate, was 2,647 (range: 364 in Puerto Rico to 6,726 in Massachusetts). ART use exceeded the national average in 13 reporting areas (Connecticut, Delaware, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Virginia). Eight reporting areas (Connecticut, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Jersey, and New York) had rates of ART use exceeding 1.5 times the national average. Nationally, among ART transfer procedures in patients using fresh embryos from their own eggs, the average number of embryos transferred increased with increasing age of the woman (1.7 among women aged <35 years, 1.9 among women aged 35-37 years, and 2.3 among women aged >37 years). Among women aged <35 years, who typically are considered to be good candidates for elective single embryo transfer (eSET) procedures, the national eSET rate was 28.5% (range: 4.3% in Puerto Rico to 67.9% in Delaware). In 2014, ART contributed to 1.6% of all infants born in the United States (range: 0.4% in Puerto Rico to 4.7% in Massachusetts) and 18.3% of all multiple-birth infants (range: 5.5% in Alaska and West Virginia to 37.3% in Hawaii), including 18.0% of all twin infants (range: 5.2% in some states to 36.2% in Hawaii) and 26.4% of all triplets and higher-order infants (range: 0% in some states to 65.2% in Hawaii). Percentages of live births that were multiple-birth deliveries were higher among infants conceived with ART (39.4%; 11.5% in Delaware to 55.6% in Puerto Rico) than among all infants born in the total birth population (3.5%; 2.2% in Puerto Rico to 4.4% in New Jersey). Approximately 38.0% of ART-conceived infants were twin infants, and 2.0% were triplets and higher-order infants. ART-conceived twins accounted for approximately 95.3% of all ART-conceived infants born in multiple deliveries. Nationally, infants conceived with ART contributed to 5.5% of all low birthweight (<2,500 g) infants (range: 1.2% in West Virginia to 14.2% in Massachusetts). Among ART-conceived infants, 27.8% were low birthweight (range: 10.6% in Delaware to 44.4% in Puerto Rico), compared with 8.0% among all infants (range: 5.9% in Alaska to 11.3% in Mississippi). ART-conceived infants contributed to 4.7% of all preterm (<37 weeks) infants (range: 1.2% in Puerto Rico to 13.4% in Massachusetts). Percentages of preterm births were higher among infants conceived with ART (33.2%; 18.9% in the District of Columbia to 45.9% in Puerto Rico) than among all infants born in the total birth population (11.3%; 8.5% in California to 16.0% in Mississippi). The percentage of ART-c
Delphinidin anthocyanins have previously been associated with the inhibition of glucose absorption. Blood glucose lowering effects have been ascribed to maqui berry (Aristotelia chilensis) extracts in humans after boiled rice consumption. In this study, we aimed to explore whether a standardized delphinidin-rich extract from maqui berry (Delphinol) affects glucose metabolism in prediabetic humans based on glycemia and insulinemia curves obtained from an oral glucose tolerance test (OGTT) after a challenge with pure glucose. Volunteers underwent four consecutive OGTTs with at least one week washout period, in which different doses of Delphinol were administered one hour before glucose intake. Delphinol significantly and dose-dependently lowered basal glycemia and insulinemia. Lower doses delayed postprandial glycemic and insulinemic peaks, while higher doses reversed this tendency. Glycemia peaks were dose-dependently lowered, while insulinemia peaks were higher for the lowest dose and lower for other doses. The total glucose available in blood was unaffected by treatments, while the total insulin availability was increased by low doses and decreased by the highest dose. Taken together, these open exploratory results suggest that Delphinol could be acting through by inhibition of intestinal glucose transporters, by an incretin-mediated effect, or by improving insulin sensitivity.
Bone HealthTrabecular Bone ScoreDXA DensitometryDevice Comparison
Trabecular bone score (TBS) is a gray-level texture measure derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images that predicts fractures independent of bone mineral density (BMD). Increased abdominal soft tissue in individuals with elevated body mass index (BMI) absorbs more X-rays during image acquisition for BMD measurement and must be accommodated by the TBS algorithm. We aimed to determine if the relationship between BMI and TBS varied between 2 major manufacturers' densitometers, because different densitometers accommodate soft tissues differently. We identified 1919 women and 811 men, participants of the Canadian Multicentre Osteoporosis Study, aged ≥40 yr with lumbar spine DXA scans acquired on GE Lunar (4 centers) or Hologic (3 centers) densitometers at year 10 of follow-up. TBS was calculated for L1-L4 (TBS iNsight® software, version 2.1). A significant negative correlation between TBS and BMI was observed when TBS measurements were performed on Hologic densitometers in men (Pearson r = -0.36, p <0.0001) and in women (Pearson r = -0.33, p <0.0001); significant correlations were not seen when TBS was measured on GE Lunar densitometers (Pearson r = 0.00 in men, Pearson r = -0.02 in women). Age-adjusted linear regression models confirmed significant interactions between BMI and densitometer manufacturer for both men and women (p < 0.0001). In contrast, comparable positive correlations were observed between BMD and BMI on both Hologic and GE Lunar densitometers in men and women. In conclusion, BMI significantly affects TBS values in men and women when measured on Hologic but not GE Lunar densitometers. This finding has implications for clinical and research applications of TBS, especially when TBS is measured sequentially on DXA densitometers from different manufacturers or when results from different machines are pooled for analysis.
We review the general topic of traumatic brain injury (TBI) and our research utilizing transcranial photobiomodulation (tPBM) to improve cognition in chronic TBI using red/near-infrared (NIR) light-emitting diodes (LEDs) to deliver light to the head. tPBM improves mitochondrial function increasing oxygen consumption, production of adenosine triphosphate (ATP), and improving cellular energy stores. Nitric oxide is released from the cells increasing regional blood flow in the brain. In our previously published study, 11 chronic TBI patients with closed-head TBI caused by different accidents (motor vehicle accident, sports-related, improvised explosive device blast injury) and exhibiting long-lasting cognitive dysfunction received 18 outpatient treatments (Monday, Wednesday, Friday for 6 weeks) starting at 10 months to 8 years post-TBI. LED therapy is nonthermal, painless, and noninvasive. An LED-based device classified as nonsignificant risk (FDA cleared) was used. Each LED cluster head (5.35 cm diameter, 500 mW, 22.2 mW/cm(2)) was applied for 9 min 45 sec (13 J/cm(2)) using 11 midline from front-to-back hairline and bilaterally on frontal, parietal, and temporal areas. Testing was performed before and after transcranial LED (tLED; at 1 week, 1 month, and at 2 months after the 18th treatment) and showed significant improvements in executive function and verbal memory. There were also fewer post-traumatic stress disorder (PTSD) symptoms reported. Ongoing, current studies involve TBI patients who have been treated with tLED using either 26 J/cm(2) per LED location on the head or treated with intranasal only (iLED) using red (633 nm) and NIR (810 nm) diodes placed into the nostrils. The NIR iLED is hypothesized to deliver photons to the hippocampus, and the red 633 nm iLED is believed to increase melatonin. Results have been similar to the previously published tLED study. Actigraphy sleep data showed increased time asleep (on average one additional hour per night) after the 18th tLED or iLED treatment. LED treatments may be performed in the home. Sham-controlled studies with veterans who have cognitive dysfunction from Gulf War Illness, blast TBI, and TBI/PTSD are currently ongoing.
Fertility AwarenessElectronic Fertility MonitoringTypical and Perfect UseOnline Programs
Fehring RJ et al., 2016·MCN Am J Matern Child Nurs
The aims of this study were to determine and compare extended use-effectiveness of an online nurse-managed fertility education service program among women (and subgroups of women) seeking to avoid pregnancy. This was a 24-month prospective study of a university-based online Web site with 663 nonbreastfeeding women using an online charting system to avoid pregnancy. Participants tracked their fertility online with either cervical mucus monitoring, electronic hormonal fertility monitoring, or both fertility indicators. Unintended pregnancies were validated by professional nurses. Participants had a mean age of 30.4 years (SD = 6.3) and mean 1.7 children (SD = 2.0). Among the 663 nonbreastfeeding participants there were 2 unintended pregnancies per 100 at 24 cycles of correct use and 15 pregnancies at 24 cycles of typical use. However, the 212 women using the electronic fertility monitor had a typical use unintended pregnancy rate of 6 at 24 cycles of use in comparison with the 118 women using cervical mucus monitoring that had a typical use pregnancy rate of 19 at 24 cycles and with the 333 women using both fertility indicators that had a pregnancy rate of 18 at 24 cycles of use. Use of the fertility monitor to estimate fertility among nonbreastfeeding women provides the most secure method of avoiding pregnancy.
Gibson-Helm M et al., 2016·J Clin Endocrinol Metab
Polycystic ovary syndrome (PCOS) is a complex, chronic, and under-recognized disorder. Diagnosis experience may have lasting effects on well-being and self-management. To investigate PCOS diagnosis experiences, information provided, and concerns about PCOS.
Cross-sectional study using an online questionnaire.
Recruitment via support group web sites in 2015 to 2016. There were 1385 women with a reported diagnosis of PCOS who were living in North America (53.0%), Europe (42.2%), or other world regions (4.9%); of these, 64.8% were 18 to 35 years of age. Satisfaction with PCOS diagnosis experience, satisfaction with PCOS information received at the time of diagnosis, and current concerns about PCOS. One-third or more of women reported >2 years (33.6%) and ≥3 health professionals (47.1%) before a diagnosis was established. Few were satisfied with their diagnosis experience (35.2%) or with the information they received (15.6%). Satisfaction with information received was positively associated with diagnosis satisfaction [odds ratio (OR), 7.0; 95% confidence interval (CI), 4.9 to 9.9]; seeing ≥5 health professionals (OR, 0.5; 95% CI, 0.3 to 0.8) and longer time to diagnosis (>2 years; OR, 0.4; 95% CI, 0.3 to 0.6) were negatively associated with diagnosis satisfaction (independent of time since diagnosis, age, and world region). Women's most common concerns were difficulty losing weight (53.6%), irregular menstrual cycles (50.8%), and infertility (44.5%). In the largest study of PCOS diagnosis experiences, many women reported delayed diagnosis and inadequate information. These gaps in early diagnosis, education, and support are clear opportunities for improving patient experience.
James AH, 2016·Hematology American Society of Hematology Education Program
Heavy menstrual bleeding (HMB), which is the preferred term for menorrhagia, affects approximately 90% of women with an underlying bleeding disorder and approximately 70% of women on anticoagulation. HMB can be predicted on the basis of clots of >=1 inch diameter, low ferritin, and 'flooding' (a change of pad or tampon more frequently than hourly). The goal of the work-up is to determine whether there is a uterine/endometrial cause, a disorder of ovulation, or a disorder of coagulation. HMB manifest by flooding and/or prolonged menses, or HMB accompanied by a personal or family history of bleeding is very suggestive of a bleeding disorder and should prompt a referral to a hematologist. The evaluation will include the patient's history, pelvic examination, and/or pelvic imaging, and a laboratory assessment for anemia, ovulatory dysfunction, underlying bleeding disorder, and in the case of the patient on anticoagulation, assessment for over anticoagulation. The goal of treatment is to reduce HMB. Not only will the treatment strategy depend on whether there is ovulatory dysfunction, uterine pathology, or an abnormality of coagulation, the treatment strategy will also depend on the age of the patient and her desire for immediate or long-term fertility. Hemostatic therapy for HMB may serve as an alternative to hormonal or surgical therapy, and may even be life-saving when used to correct an abnormality of coagulation.
Endometriosis is characterized by frequent recurrences of symptoms and lesions even after extirpative surgery. Because medical therapies control but do not cure the disease, long periods of pharmacologic management may be needed until pregnancy desire or, sometimes, physiologic menopause. Hormonal drugs suppress ovulation and menstruation and have similar beneficial effects against pain. However, only estrogen-progestins and progestins have safety/tolerability/cost profiles that allow long-term use. These compounds induce atrophy of eutopic and ectopic endometrium, have antiinflammatory and proapoptotic properties, and can be delivered via different modalities, including oral, transdermal, subcutaneous, intramuscular, vaginal, and intrauterine routes. At least two-thirds of symptomatic women are relieved from pain and achieve appreciable improvements in health-related quality of life. Progesterone resistance may cause nonresponse in the remaining one-third. When using estrogen-progestins continuously, individualized, tailored cycling should be explained to improve compliance. All combinations demonstrated a similar effect on dysmenorrhea, independently from progestin type. Estrogen-progestins with the lowest possible estrogen dose should be chosen to combine optimal lesion suppression and thrombotic risk limitation. Progestins should be suggested in women who do not respond or manifest intolerance to estrogen-progestins and in those with dyspareunia and/or deep lesions. Progestins do not increase significantly the thrombotic risk and generally may be used when estrogens are contraindicated. Estrogen-progestins and progestins reduce the incidence of postoperative endometrioma recurrence and show a protective effect against endometriosis-associated epithelial ovarian cancer risk.
The aim of this study was to evaluate the effect of vitamin D supplementation in women with hypovitaminosis D and "small burden" uterine fibroids.This study focused on 208 women diagnosed with uterine fibroids and concomitant hypovitaminosis D, from January to December 2014. One hundred eight women of the initial study population were diagnosed with "small burden" uterine fibroids. Among them, those who underwent a proper vitamin D supplementation constituted the "study group" (n = 53), while women who spontaneously refused the therapy or did not perform it properly, constituted the "control group" (n = 55). The characteristics of uterine fibroids, the fibroid-related symptoms, and the vitamin D serum levels were evaluated 12 months after the initial diagnosis.In women with uterine fibroids, a negative correlation emerged between the baseline 25-hydroxy-cholecalciferol (25-OH-D3) concentration and both the volume of the largest fibroid (r = -0.18, P = 0.01) and the total volume of fibroids (r = -0.19, P = 0.01). No correlation was found between the baseline 25-OH-D3 levels and the number of fibroids per patient (r = -0.10, P = 0.16). In women of the "study group," a significant increase in the 25-OH-D3 serum level was observed after 12 months of supplementation, and a lower rate of surgical or medical treatment due to the "progression to extensive disease" was reported (13.2% vs 30.9%, P = 0.05).Supplementation therapy with 25-OH-D3 restores normal vitamin D serum levels in women with "small burden" fibroids. In these women, vitamin D supplementation seems to reduce the progression to an extensive disease, and thus the need of conventional surgical or medical therapy.
Which outcome measures are reported in RCTs for IVF? Many combinations of numerator and denominator are in use, and are often employed in a manner that compromises the validity of the study. The choice of numerator and denominator governs the meaning, relevance and statistical integrity of a studys results. RCTs only provide reliable evidence when outcomes are assessed in the cohort of randomised participants, rather than in the subgroup of patients who completed treatment. STUDY DESIGN, SIZE, Review of outcome measures reported in 142 IVF RCTs published in 2013 or 2014. PARTICIPANTS/MATERIALS, SETTING, Trials were identified by searching the Cochrane Gynaecology and Fertility Specialised Register. English-language publications of RCTs reporting clinical or preclinical outcomes in peer-reviewed journals in the period 1 January 2013 to 31 December 2014 were eligible. Reported numerators and denominators were extracted. Where they were reported, we checked to see if live birth rates were calculated correctly using the entire randomised cohort or a later denominator. MAIN Over 800 combinations of numerator and denominator were identified (613 in no more than one study). No single outcome measure appeared in the majority of trials. Only 22 (43%) studies reporting live birth presented a calculation including all randomised participants or only excluding protocol violators. A variety of definitions were used for example, a consensus regarding what should constitute an ongoing pregnancy does not appear to exist at present. LIMITATIONS, Several of the included articles may have been secondary publications. Our categorisation scheme was essentially arbitrary, so the frequencies we present should be interpreted with this in mind. The analysis of live birth denominators was post hoc. There is massive diversity in numerator and denominator selection in IVF trials due to its multistage nature, and this causes methodological frailty in the evidence base. The twin spectres of outcome reporting bias and analysis of non-randomised comparisons do not appear to be widely recognised. Initiatives to standardise outcome reporting, such as requiring all effectiveness studies to report live birth or cumulative live birth, are welcome. However, there is a need to recognise that early outcomes of treatment, such as stimulation response or embryo quality, may be appropriate choices of primary outcome for early phase studies.
Oral contraceptive pills have been implicated in the pathophysiology of breast cancer. Although many studies have examined the relationship between combined oral contraceptives (COCs) and breast cancer, there is a paucity of literature that discusses progestin-only oral contraceptives (POCs) and breast cancer. The purpose of this investigation is to examine potential associations between different types of oral contraceptives and breast cancer mortality in the South Carolina Medicaid population among different racial/ethnic groups. Subjects included 4816 women diagnosed with breast cancer between 2000 and 2013. Kaplan-Meier curves were calculated to determine time-to-mortality rates among users of oral contraceptives. Competing-risks models and Cox multivariate survival models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer and other-cause mortality, as well as all-cause mortality. POCs were associated with a significantly decreased risk of breast cancer mortality (HR: 0.07; 95% CI: 0.01, 0.52) and a non-significant increased risk of all-cause mortality (HR: 1.04; 95% CI: 0.52, 2.07). COCs increased the risk of breast cancer mortality (HR: 1.61; 95% CI: 1.14, 2.28) and all-cause mortality (HR: 1.83; 95% CI: 1.30, 2.57). Use of POCs may be associated with a decreased risk of breast cancer mortality. Due to the small sample size of POC users in the current study, additional research is needed to confirm these findings.
Most premenopausal women with low trauma fracture(s) or low bone mineral density have a secondary cause of osteoporosis or bone loss. Where possible, treatment of the underlying cause should be the focus of management. Premenopausal women with an ongoing cause of bone loss and those who have had, or continue to have, low trauma fractures may require pharmacologic intervention. Clinical trials provide evidence of benefits of bisphosphonates and teriparatide for bone mineral density in several types of premenopausal osteoporosis, but studies are small and do not provide evidence regarding fracture risk reduction.
Goldstein CA et al., 2016·Current Sleep Medicine Reports
Adequate sleep is crucial for general health and wellbeing. Although the neuronal control of the reproductive axis and sleep-generating neurons share an anatomical location, little is known regarding the impact of sleep and circadian disruption on fertility in women. Animal models have established clear circadian control of the pre-ovulatory luteinizing hormone surge. Additionally, disruption of the circadian timing system by exposure to abnormal light-dark cycles or mutations of core clock genes results in diminished reproductive capacity in animals. Abnormalities in menstruation, fertility, and early pregnancy maintenance in female shift workers provide evidence for a role of circadian rhythms in the reproductive health of women. Reproductive hormones may modify sleep, and the relationship is bidirectional such that sleep disruption may alter the profile of reproductive hormone secretion. Therefore, sleep, apart from its circadian timing, may also have relevance in attaining pregnancy. Additionally, infertility is associated with psychological distress which may result in poor quality sleep. The interaction between psychological distress and disturbed sleep in reproduction has garnered minimal attention and may be a crucial factor to consider during the evaluation and treatment of infertility. This work reviews animal models and evidence in women that suggest a role for sleep and circadian rhythms in reproductive health and reveals areas that require future investigation.
Recent studies have identified that levonorgestrel administered orally in emergency contraception (LNG-EC) is only efficacious when taken before ovulation. However, the drug does not consistently prevent follicular rupture or impair sperm function. The present systematic review is performed to analyze and more precisely define the extent to which pre-fertilization mechanisms of action may explain the drug's efficacy in pregnancy avoidance. We also examine the available evidence to determine if pre-ovulatory drug administration may be associated with post-fertilization effects. The mechanism of action of LNG-EC is reviewed. The drug has no ability to alter sperm function at doses used in vivo and has limited ability to suppress ovulation. Our analysis estimates that the drug's ovulatory inhibition potential could prevent less than 15 percent of potential conceptions, thus making a pre-fertilization mechanism of action significantly less likely than previously thought. Luteal effects (such as decreased progesterone, altered glycodelin levels, and shortened luteal phase) present in the literature may suggest a pre-ovulatory induced post-fertilization drug effect. Plan B is the most widely used emergency contraceptive available. It is important for patients and physicians to clearly understand the drug's mechanism of action (MOA). The drug was originally thought to work by preventing fertilization. Recent research has cast doubt on this. Our review of the research suggests that it could act in a pre-fertilization capacity, and we estimate that it could prevent ovulation in only 15 percent or less of cases. The drug has no ability to alter sperm function and limited ability to suppress ovulation. Further, data suggest that when administered pre-ovulation, it may have a post-fertilization MOA.
This paper is a response to Dr. Kathleen Raviele's recent article on her critical analysis of the use of levonorgestrel given to women postsexual assault and her suggestion that the use of Meloxicam may be an ethical alternative.
Various fertility indicators are used by natural family planning methods to identify the fertile and infertile phases of a woman's mucus observations, cycle-day probabilities, basal body temperature readings, and hormonal measures of LH and estrogen. Simplified NFP methods generally make use of a single fertility indicator such as cycle-day probabilities (Standard Days Method) or mucus observations (Billings Ovulation Method). The Couple Bead Method integrates the two simplest fertility indicators, cycle-day probabilities and mucus observations, expanding its applicability to all women, regardless of cycle regularity and length. In determining cycle-day probabilities, the Couple Bead Method relies on a new data set from ultrasound-derived determinants of gestational age that more directly define the day of conception and the fertile window. By using a visual-based system of inexpensive colored beads, the Couple Bead Method can be used by couples of all educational and income levels. Natural family planning methods provide education in regard to the signs of a woman's body which indicate if she is possibly fertile or not. Two important signs are the day of her menstrual cycle and her observations of bleeding and cervical mucus or dryness. The Couple Bead Method teaches a couple how to observe these signs and chart them with a system of colored beads. The Couple Bead Method can be used by women with regular or irregular cycles. The bead sets are inexpensive and consist of a length of plastic cord, colored "pony beads" and safety pins.
This review explains the main effects exerted by sex steroids and other hormones on the adolescent brain. During the transition from puberty to adolescence, these hormones participate in the organizational phenomena that structurally shape some brain circuits. In adulthood, this will propitiate some specific behavior as responses to the hormones now activating those neural circuits. Adolescence is, then, a critical "organizational window" for the brain to develop adequately, since steroid hormones perform important functions at this stage. For this reason, the adolescent years are very important for future behaviors in human beings. Changes that occur or fail to occur during adolescence will determine behaviors for the rest of one's lifetime. Consequently, understanding the link between adolescent behavior and brain development as influenced by sex steroids and other hormones and compounds is very important in order to interpret various psycho-affective pathologies. The effect of steroid hormones on the development of the adolescent brain, and therefore, on adolescent behavior, is noticeable. This review presents their main activational and organizational effects. During the transition from puberty to adolescence, organizational phenomena triggered by steroids structurally affect the remodeling of brain circuits. Later in adulthood, these changes will be reflected in behavioral responses to such hormones. Adolescence can then be seen as a fundamental "organizational window" during which sex steroids and other hormones and compounds play relevant roles. The understanding of the relationship between adolescent behavior and the way hormones influence brain development help understand some psychological disorders.
EndometriosisPrevalencePelvic Pain and DyspareuniaCross-Sectional Survey
To estimate the prevalence of diagnosed endometriosis (DE) in women in the United States and assess the associated symptomatic burden. An online, cross-sectional survey of women aged 18-49 years was conducted from August 6, 2012, through November 14, 2012. Survey data (weighted by age, race, education, income, geographical distribution, and propensity score) were used to estimate the prevalence and symptomatic burden of DE in women in the United States. Weighted logistic regressions were used to assess differences in symptom burden between women with and without endometriosis. The prevalence of DE was estimated at 6.1% (2,922 of 48,020 women surveyed); 52.7% of women were 18-29 years of age when they were diagnosed with endometriosis. Most (86.2%) women experienced symptoms before diagnosis. More women with (vs. without) DE had menstrual pelvic pain/cramping (52.7 vs. 45.2%), non-menstrual pelvic pain/cramping (36.7 vs. 14.3%), infertility (11.6 vs. 3.4%), and dyspareunia (29.5 vs. 13.4%). Women with endometriosis were also more likely to report severe symptoms (OR (95% CI) 2.7 (2.3-3.1) for menstrual pelvic pain/cramping, 2.2 (1.7-2.9) for non-menstrual pelvic pain/cramping, and 2.4 (1.8-3.2) for dyspareunia). The prevalence of DE among US women is notable, and affected women experience a substantial symptom burden.
Insulin resistance (IR) plays a pivotal role in PCOS. Insulin-sensitizer agents such as metformin and inositols have been shown to improve the endocrine and metabolic aspects of PCOS. The purpose of this study is to compare their effects on the clinical and metabolic features of the women with PCOS. Fifty PCOS women with IR and/or hyperinsulinemia were randomized to treatment with metformin (1500 mg/day) or myo-inositol (4 g/day). IR was defined as HOMA-IR >2.5, while hyperinsulinemia was defined as a value of AUC for insulin after a glucose load over the cutoff of our laboratory obtained in normal women. The Matsusa Index has been calculated. The women have been evaluated for insulin secretion, BMI, menstrual cycle length, acne and hirsutism, at baseline and after 6 months of therapy. The results obtained in both groups were similar. The insulin sensitivity improved in both treatment groups. The BMI significantly decreased and the menstrual cycle was normalized in about 50% of the women. No significant changes in acne and hirsutism were observed. The two insulin-sensitizers, metformin and myo-inositol, show to be useful in PCOS women in lowering BMI and ameliorating insulin sensitivity, and improving menstrual cycle without significant differences between the two treatments.
Contraception/ComparisonDepression and MoodCombined and Progestin-OnlyProspective Cohort
Millions of women worldwide use hormonal contraception. Despite the clinical evidence of an influence of hormonal contraception on some women's mood, associations between the use of hormonal contraception and mood disturbances remain inadequately addressed. To investigate whether the use of hormonal contraception is positively associated with subsequent use of antidepressants and a diagnosis of depression at a psychiatric hospital. DESIGN, SETTING, This nationwide prospective cohort study combined data from the National Prescription Register and the Psychiatric Central Research Register in Denmark. All women and adolescents aged 15 to 34 years who were living in Denmark were followed up from January 1, 2000, to December 2013, if they had no prior depression diagnosis, redeemed prescription for antidepressants, other major psychiatric diagnosis, cancer, venous thrombosis, or infertility treatment. Data were collected from January 1, 1995, to December 31, 2013, and analyzed from January 1, 2015, through April 1, 2016. Use of different types of hormonal contraception. With time-varying covariates, adjusted incidence rate ratios (RRs) were calculated for first use of an antidepressant and first diagnosis of depression at a psychiatric hospital. A total of 1 061 997 women (mean [SD] age, 24.4 [0.001] years; mean [SD] follow-up, 6.4 [0.004] years) were included in the analysis. Compared with nonusers, users of combined oral contraceptives had an RR of first use of an antidepressant of 1.23 (95% CI, 1.22-1.25). Users of progestogen-only pills had an RR for first use of an antidepressant of 1.34 (95% CI, 1.27-1.40); users of a patch (norgestrolmin), 2.0 (95% CI, 1.76-2.18); users of a vaginal ring (etonogestrel), 1.6 (95% CI, 1.55-1.69); and users of a levonorgestrel intrauterine system, 1.4 (95% CI, 1.31-1.42). For depression diagnoses, similar or slightly lower estimates were found. The relative risks generally decreased with increasing age. Adolescents (age range, 15-19 years) using combined oral contraceptives had an RR of a first use of an antidepressant of 1.8 (95% CI, 1.75-1.84) and those using progestin-only pills, 2.2 (95% CI, 1.99-2.52). Six months after starting use of hormonal contraceptives, the RR of antidepressant use peaked at 1.4 (95% CI, 1.34-1.46). When the reference group was changed to those who never used hormonal contraception, the RR estimates for users of combined oral contraceptives increased to 1.7 (95% CI, 1.66-1.71). Use of hormonal contraception, especially among adolescents, was associated with subsequent use of antidepressants and a first diagnosis of depression, suggesting depression as a potential adverse effect of hormonal contraceptive use.
Trabecular bone score is a gray-level textural measure obtained from dual energy x-ray absorptiometry lumbar spine images that provides information independent of areal bone mineral density. The association between trabecular bone score and incident fractures in adults with reduced kidney function and whether this association differs from that of adults with normal kidney function are unknown. DESIGN, SETTING, PARTICIPANTS, & We included 1426 participants ages ≥40 years old (mean age of 67 years) in the community-based Canadian Multicentre Osteoporosis Study. We stratified participants at cohort entry (2005-2008) by eGFR (eGFR<60 ml/min per 1.73 m2 [n=199; 72.4% stage 3a, 25.1% stage 3b, and 2.5% stage 4] versus ≥60 ml/min per 1.73 m2 [n=1227]). Trabecular bone score was obtained from lumbar spine (L1-L4) dual energy x-ray absorptiometry images, with a lower trabecular bone score representing worse bone structure. Over an average of 4.7 years follow-up (maximum follow-up of 5 years), we documented incident fragility (low-trauma) fracture events (excluding craniofacial, foot, and hand sites). We used a modified Kaplan-Meier estimator to determine the 5-year probability of fracture. Cox proportional hazard regression per SD lower trabecular bone score expressed the gradient of fracture risk. Individuals with an eGFR<60 ml/min per 1.73 m2 who had a trabecular bone score value below the median (<1.277) had a significantly higher 5-year fracture probability than those above the median (18.1% versus 6.2%; P=0.01). The association between trabecular bone score and fracture was independent of bone mineral density and other clinical risk factors in adults with reduced and normal kidney function (adjusted hazard ratio per eGFR<60 ml/min per 1.73 m2: adjusted hazard ratio, 1.62; 95% confidence interval, 1.04 to 2.51; eGFR≥60 ml/min per 1.73 m2: adjusted hazard ratio, 1.44; 95% confidence interval, 1.13 to 1.83). Lower lumbar spine trabecular bone score is independently associated with a higher fracture risk in adults with reduced kidney function. Additional study is needed to examine the association between trabecular bone score and fractures in individuals with diagnosed CKD-mineral and bone disorder.
InfertilityDelayed ChildbearingPrevalence in Specific PopulationsCareer and Fertility
Female physicians may experience unique challenges regarding fertility and family planning. We sought to determine childbearing patterns and decision-making among American female physicians. In 2012-2013, we surveyed a random sample of 600 female physicians who graduated medical school between 1995 and 2000. Primary outcome measures included fertility and childbearing history, reflections regarding decision-making, perceptions of workplace support, and estimations of childbearing potential. Response rate was 54.5% (327/600). A majority (82.0%) of the sample were parents, 77.4% had biological children with an average of 2.3 children. Average age at medical school graduation was 27.5 years, at completion of training (completion of medical school, residency, and/or fellowship) was 31.6 years, and at first pregnancy was 30.4 years. Nearly one quarter (24.1%) of respondents who had attempted conception were diagnosed with infertility, with an average age at diagnosis of 33.7 years. Among those with infertility, 29.3% reported diminished ovarian reserve. When asked what they would do differently in retrospect, most respondents (56.8%) would do nothing differently regarding fertility/conception/childbearing, 28.6% would have attempted conception earlier, 17.1% would have gone into a different specialty, and 7.0% would have used cryopreservation to extend fertility. Fewer of those whose first pregnancy was in medical school perceived substantial workplace support (68.2%) than those whose first pregnancies followed training (88.6%). A substantial proportion of female physicians have faced infertility or have regrets about family planning decisions and career decision-making. Combining a medical career with motherhood continues to pose challenges, meriting further investigation and targeted support.
Endometriosis is a complex, inflammatory disease that affects 6-10% of reproductive-aged women. Almost half of the women with endometriosis experience infertility. Despite the excessive prevalence, the pathogenesis of endometriosis and its associated infertility is unknown and a cure is not available. While many theories have been suggested to link endometriosis and infertility, a consensus among investigators has not emerged. In this extensive review of the literature as well as research from our laboratory, we provide potential insights into the role of immune dysfunction in endometriosis associated infertility. We discuss the implication of the peritoneal inflammatory microenvironment on various factors that contribute to infertility such as hormonal imbalance, oxidative stress and how these could further lead to poor oocyte, sperm and embryo quality, impaired receptivity of the endometrium and implantation failure.
Buck Louis GM et al., 2016·J Womens Health (Larchmt)
Endometriosis is a gynecologic disease reported to be associated with infertility and, possibly, adverse pregnancy outcomes. While considerable research focuses on pregnancy outcomes following diagnosis and/or treatment, few data actually describe women's reproductive history before diagnosis for a more complete understanding of endometriosis and reproduction. The study sample comprised 473 women (aged 18-44 years) undergoing laparoscopies or laparotomies, irrespective of surgical indication at 14 clinical sites, during the period 2007-2009. Upon enrollment and before surgery, women were queried about pregnancy intentions and the time required to become pregnant for planned pregnancies. Endometriosis was defined as surgically visualized disease. Using discrete time survival analysis, we estimated fecundability odds ratios (FORs) and 95% confidence intervals (CIs) to assess time to pregnancy (TTP) after adjusting for potential confounders (age, body composition, cigarette smoking, site). Generalized estimating equations accounted for multiple pregnancy attempts per woman. FORs ResultsApproximately 66% and 69% of women with and without endometriosis, respectively, reported having a planned pregnancy before surgery, respectively. After adjustment, an endometriosis diagnosis was associated with ≈29% reduction in fecundity or a longer TTP across all pregnancy-trying attempts (adjusted FOR = 0.71; 95% CI 0.46-1.10). While FORs were consistently ConclusionsWomen with endometriosis had a longer TTP than unaffected women, irrespective of disease severity, although the findings did not achieve significance. Prior reproductive history may be informative for predicting fecundity and pregnancy outcomes following diagnosis/treatment.
Polycystic ovary syndrome (PCOS) was hypothesized to result from functional ovarian hyperandrogenism (FOH) due to dysregulation of androgen secretion in 1989-1995. Subsequent studies have supported and amplified this hypothesis. When defined as otherwise unexplained hyperandrogenic oligoanovulation, two-thirds of PCOS cases have functionally typical FOH, characterized by 17-hydroxyprogesterone hyperresponsiveness to gonadotropin stimulation. Two-thirds of the remaining PCOS have FOH detectable by testosterone elevation after suppression of adrenal androgen production. About 3% of PCOS have a related isolated functional adrenal hyperandrogenism. The remaining PCOS cases are mild and lack evidence of steroid secretory abnormalities; most of these are obese, which we postulate to account for their atypical PCOS. Approximately half of normal women with polycystic ovarian morphology (PCOM) have subclinical FOH-related steroidogenic defects. Theca cells from polycystic ovaries of classic PCOS patients in long-term culture have an intrinsic steroidogenic dysregulation that can account for the steroidogenic abnormalities typical of FOH. These cells overexpress most steroidogenic enzymes, particularly cytochrome P450c17. Overexpression of a protein identified by genome-wide association screening, differentially expressed in normal and neoplastic development 1A.V2, in normal theca cells has reproduced this PCOS phenotype in vitro. A metabolic syndrome of obesity-related and/or intrinsic insulin resistance occurs in about half of PCOS patients, and the compensatory hyperinsulinism has tissue-selective effects, which include aggravation of hyperandrogenism. PCOS seems to arise as a complex trait that results from the interaction of diverse genetic and environmental factors. Heritable factors include PCOM, hyperandrogenemia, insulin resistance, and insulin secretory defects. Environmental factors include prenatal androgen exposure and poor fetal growth, whereas acquired obesity is a major postnatal factor. The variety of pathways involved and lack of a common thread attests to the multifactorial nature and heterogeneity of the syndrome. Further research into the fundamental basis of the disorder will be necessary to optimally correct androgen levels, ovulation, and metabolic homeostasis.
Botanical dietary supplements are increasingly popular for women's health, particularly for older women. The specific botanicals women take vary as a function of age. Younger women will use botanicals for urinary tract infections, especially Vaccinium macrocarpon (cranberry), where there is evidence for efficacy. Botanical dietary supplements for premenstrual syndrome (PMS) are less commonly used, and rigorous clinical trials have not been done. Some examples include Vitex agnus-castus (chasteberry), Angelica sinensis (dong quai), Viburnum opulus/prunifolium (cramp bark and black haw), and Zingiber officinale (ginger). Pregnant women have also used ginger for relief from nausea. Natural galactagogues for lactating women include Trigonella foenum-graecum (fenugreek) and Silybum marianum (milk thistle); however, rigorous safety and efficacy studies are lacking. Older women suffering menopausal symptoms are increasingly likely to use botanicals, especially since the Women's Health Initiative showed an increased risk for breast cancer associated with traditional hormone therapy. Serotonergic mechanisms similar to antidepressants have been proposed for Actaea/Cimicifuga racemosa (black cohosh) and Valeriana officinalis (valerian). Plant extracts with estrogenic activities for menopausal symptom relief include Glycine max (soy), Trifolium pratense (red clover), Pueraria lobata (kudzu), Humulus lupulus (hops), Glycyrrhiza species (licorice), Rheum rhaponticum (rhubarb), Vitex agnus-castus (chasteberry), Linum usitatissimum (flaxseed), Epimedium species (herba Epimedii, horny goat weed), and Medicago sativa (alfalfa). Some of the estrogenic botanicals have also been shown to have protective effects against osteoporosis. Several of these botanicals could have additional breast cancer preventive effects linked to hormonal, chemical, inflammatory, and/or epigenetic pathways. Finally, although botanicals are perceived as natural safe remedies, it is important for women and their healthcare providers to realize that they have not been rigorously tested for potential toxic effects and/or drug/botanical interactions. Understanding the mechanism of action of these supplements used for women's health will ultimately lead to standardized botanical products with higher efficacy, safety, and chemopreventive properties.
Pelvic inflammatory disease (PID) and more specifically salpingitis (visually confirmed inflammation) is the primary cause of tubal factor infertility and is an important risk factor for ectopic pregnancy. The risk of these outcomes increases following repeated episodes of PID. We developed a homogenous discrete-time Markov model for the distribution of PID history in the UK. We used a Bayesian framework to fully propagate parameter uncertainty into the model outputs. We estimated the model parameters from routine data, prospective studies, and other sources. We estimated that for women aged 35-44 years, 33·6% and 16·1% have experienced at least one episode of PID and salpingitis, respectively (diagnosed or not) and 10·7% have experienced one salpingitis and no further PID episodes, 3·7% one salpingitis and one further PID episode, and 1·7% one salpingitis and ⩾2 further PID episodes. Results are consistent with numerous external data sources, but not all. Studies of the proportion of PID that is diagnosed, and the proportion of PIDs that are salpingitis together with the severity distribution in different diagnostic settings and of overlap between routine data sources of PID would be valuable.
The use of 2 × 2000 mg myoinositol + 2 × 200 μg folic acid per day is a safe and promising tool in the effective improvement of symptoms and infertility for patients with a polycystic ovary syndrome (PCOS). Using a questionnaire an observational study was performed under German gynecologists to collect data on ovulation and pregnancy rates in PCOS patients with infertility. In this observational study, 3602 infertile women used myoinositol and folic acid between 2 and 3 months in a dosage of 2 × 2000 mg myoinositol + 2 × 200 μg folic acid per day. In a subgroup of 32 patients, hormonal values for testosterone, free testosterone, and progesterone were analyzed before and after 12 weeks of treatment. The mean time of use was 10.2 weeks. During this time 70% of these women had a restored ovulation, and 545 pregnancies were obtained. This means a pregnancy rate of 15.1% of all the myoinositol and folic acid users. In 19 cases a concomitant medication with clomiphene or dexamethasone was used. One twin pregnancy was documented. Testosterone levels changed from 96.6 ng/ml to 43.3 ng/ml and progesterone from 2.1 ng/ml to 12.3 ng/ml (p < 0.05) after 12 weeks of treatment. No relevant side effects were present among the patients. This study could show that a new treatment option for patients with a PCOS and infertility is available. The achieved pregnancy rates are at least in an equivalent or even superior range than those reported by the use of metformin.
Repetitive transcranial magnetic stimulation (rTMS) is increasingly used as a therapeutic intervention for neuropsychiatric illnesses and has demonstrated efficacy for treatment of major depression. However, an unresolved question is whether a course of rTMS treatment results in effects on cognitive functioning. In this systematic review and meta-analysis we aimed to quantitatively determine whether a course of rTMS has cognitive enhancing effects. We examined cognitive outcomes from randomised, sham-controlled studies conducted in patients with neuropsychiatric conditions where rTMS was administered to the dorsolateral prefrontal cortex (DLPFC) across repeated sessions, searched from PubMed/MEDLINE and other databases up until October 2015. Thirty studies met our inclusion criteria. Cognitive outcomes were pooled and examined Global cognitive function, executive function, attention, working memory, processing speed, visual memory, verbal memory and visuospatial ability. Active rTMS treatment was unassociated with generalised gains across the majority of domains of cognitive functioning examined. Secondary analyses revealed a moderate sized positive effect for improved working memory in a small number of studies in patients with schizophrenia (k = 3, g = 0.507, 95 % CI = [0.183-0.831], p < .01). Therapeutic rTMS when administered to the DLPFC in patients with neuropsychiatric conditions does not result in robust cognitive enhancing effects.
InfertilityOvarian Hyperstimulation Syndrome PreventionOHSS Risk ReductionSafety Protocols
Open Access
Ovarian hyperstimulation syndrome is a potentially life-threatening, but preventable iatrogenic complication of in vitro fertilisation treatment. In recent years, new strategies have been developed to minimise the risk of ovarian hyperstimulation syndrome after in vitro fertilisation, including better at-risk patient identification prior to starting treatment, the use of a lower human chorionic gonadotrophin dose or alternative medication instead of human chorionic gonadotrophin to induce final oocyte maturation such as gonadotrophin-releasing hormone agonist and kisspeptin in antagonist cycles, cryopreservation of all embryos and delayed embryo transfer, and the use of oral dopamine agonists after oocyte retrieval. In this article, the advantages and limitations of those new developments are discussed and future directions towards establishment of an ovarian hyperstimulation syndrome–free in vitro fertilisation clinic are explored.
The aim of this systematic review was to update, complete, and critically evaluate the evidence from placebo-controlled randomized clinical trials (RCTs) of ginseng for managing menopausal women's health. We searched the literature using 13 databases (MEDLINE, AMED, EMBASE, the Cochrane Library, 6 Korean Medical, and 3 Chinese Databases) from their inception to July 2016 and included all double-blind RCTs that compared any type of ginseng with a placebo control in postmenopausal women. The methodological quality of all studies was assessed using a Cochrane risk of bias tool. Ten RCTs met our inclusion criteria. Most RCTs had unclear risk of bias. One RCT did not show a significant difference in hot flash frequency between Korean red ginseng (KRG) and placebo. The second RCT reported positive effects of KRG on menopausal symptoms. The third RCT found beneficial effects of ginseng (Ginsena) on depression, well-being, and general health. Four RCTs failed to show significant differences in various hormones between KRG and placebo controls except dehydroepiandrosterone. Two other RCTs failed to show effects of KRG on endometrial thickness in menopausal women. The other RCT also failed to show the effects of American ginseng on oxidative stress markers and other antioxidant enzymes. Our systematic review provided positive evidence of ginseng for sexual function and KRG for sexual arousal and total hot flashes score in menopausal women. However, the results of KRG or ginseng failed to show specific effects on hot flash frequency, hormones, biomarkers, or endometrial thickness. The level of evidence for these findings was low because of unclear risk of bias.
Progestin-only contraceptives (POCs) are appropriate for many women who cannot or should not take estrogen. POCs include injectables, intrauterine contraception, implants, and oral contraceptives. Many POCs are long-acting, cost-effective methods of preventing pregnancy. However, concern about weight gain can deter the initiation of contraceptives and cause early discontinuation among users. The primary objective was to evaluate the association between progestin-only contraceptive use and changes in body weight. Until 4 August 2016, we searched MEDLINE, CENTRAL, POPLINE, LILACS, ClinicalTrials.gov, and ICTRP. For the initial review, we contacted investigators to identify other trials.
We considered comparative studies that examined a POC versus another contraceptive method or no contraceptive. The primary outcome was mean change in body weight or mean change in body composition. We also considered the dichotomous outcome of loss or gain of a specified amount of weight.
Two authors extracted the data. Non-randomized studies (NRS) need to control for confounding factors. We used adjusted measures for the primary effects in NRS or the results of matched analysis from paired samples. If the report did not provide adjusted measures for the primary analysis, we used unadjusted outcomes. For RCTs and NRS without adjusted measures, we computed the mean difference (MD) with 95% confidence interval (CI) for continuous variables. For dichotomous outcomes, we calculated the Mantel-Haenszel odds ratio (OR) with 95% CI. We found 22 eligible studies that included a total of 11,450 women. With 6 NRS added to this update, the review includes 17 NRS and 5 RCTs. By contraceptive method, the review has 16 studies of depot medroxyprogesterone acetate (DMPA), 4 of levonorgestrel-releasing intrauterine contraception (LNG-IUC), 5 for implants, and 2 for progestin-only pills.Comparison groups did not differ significantly for weight change or other body composition measure in 15 studies. Five studies with moderate or low quality evidence showed differences between study arms. Two studies of a six-rod implant also indicated some differences, but the evidence was low quality.Three studies showed differences for DMPA users compared with women not using a hormonal method. In a retrospective study, weight gain (kg) was greater for DMPA versus copper (Cu) IUC in years one (MD 2.28, 95% CI 1.79 to 2.77), two (MD 2.71, 95% CI 2.12 to 3.30), and three (MD 3.17, 95% CI 2.51 to 3.83). A prospective study showed adolescents using DMPA had a greater increase in body fat (%) compared with a group not using a hormonal method (MD 11.00, 95% CI 2.64 to 19.36). The DMPA group also had a greater decrease in lean body mass (%) (MD -4.00, 95% CI -6.93 to -1.07). A more recent retrospective study reported greater mean increases with use of DMPA versus Cu IUC for weight (kg) at years 1 (1.3 vs 0.2), 4 (3.5 vs 1.9), and 10 (6.6 vs 4.9).Two studies reported a greater mean increase in body fat mass (%) for POC users versus women not using a hormonal method. The method was LNG-IUC in two studies (reported means 2.5 versus -1.3; P = 0.029); (MD 1.60, 95% CI 0.45 to 2.75). One also studied a desogestrel-containing pill (MD 3.30, 95% CI 2.08 to 4.52). Both studies showed a greater decrease in lean body mass among POC users. AUTHORS' We considered the overall quality of evidence to be low; more than half of the studies had low quality evidence. The main reasons for downgrading were lack of randomizations (NRS) and high loss to follow-up or early discontinuation.These 22 studies showed limited evidence of change in weight or body composition with use of POCs. Mean weight gain at 6 or 12 months was less than 2 kg (4.4 lb) for most studies. Those with multiyear data showed mean weight change was approximately twice as much at two to four years than at one year, but generally the study groups did not differ significantly. Appropriate counseling about typical weight gain may help reduce discontinuation of contraceptives due to perceptions of weight gain.
Contraception/ComparisonIVF SafetyIVF ProceduresEmbryo Protection
Open Access
Wdowiak A et al., 2016·Videosurgery and Other Miniinvasive Techniques
In vitro fertilization (IVF) is a method of treatment for infertility in selected indications. Recent years have brought dynamic development of technologies related to IVF. This article presents problems pertaining to the safety of technology with respect to the patient, as well as the embryo, based on an analysis of scientific reports and our own experience. Invasiveness of the IVF procedure for the woman and the embryo varies on an individual basis. Minimization of the invasiveness of IVF requires experience of the staff performing the procedure, especially with respect to the assessment of risk for an individual patient. Technologies related to IVF are constantly being improved, and the effectiveness of the selected individual treatment methods is not always scientifically confirmed.
General OB/GYNDiabetes-Related Sexual DysfunctionErectile DysfunctionDiabetes and Hormones
Deterioration in sexual functioning is one of the major and serious complications of diabetes. This common metabolic disorder not only affects sexuality through microvascular and nerve damage but also has psychological aspects. In men, the primary complications are erectile dysfunction, ejaculatory dysfunction, and loss of libido. Women similarly experience sexual problems, including decreased libido and painful intercourse. To summarize the effects of diabetes on sexuality, evaluate the impact of diabetes on sexual function, and assess the conventional and novel treatment approaches based on recent studies. A literature review of peer-reviewed journal articles and guidelines was performed. To assess the effects of diabetes on sexuality and to focus on treatment approaches. Male and female sexual dysfunctions are a significant complication of diabetes. Tight glycemic control seems to be beneficial in delaying the onset of sexual problems and ameliorating them when they are present. Erectile dysfunction occurs as one of the first problems. The current mainstay of treatment for erectile dysfunction is therapy with phosphodiesterase type 5 inhibitors and then a stepwise approach of management. Men also can experience ejaculation problems and loss of libido. Diabetes also can decrease testosterone levels, which further decreases libido. Hypogonadal men with diabetes might benefit from testosterone replacement therapy. Diabetic women also can have sexual problems. These problems mainly include loss of libido, decrease in arousal and lubrication resulting in painful intercourse, and loss of orgasm. All these challenges require a multidisciplinary approach. Diabetes has detrimental effects on the sexual function of patients. Diabetologists who primarily care for the patient should not only focus on the glycemic control of their patients but also address their sexual complaints, because these problems can significantly impair their quality of life. Urologists, gynecologists, endocrinologists, and psychiatrists should work in a multidisciplinary manner for the treatment of decreased sexual functioning as a result of diabetes.
Many factors including genetic, environmental, and acquired are involved in breast cancer development across various societies. Among all of these factors in families with a history of breast cancer throughout several generations, genetics, like predisposing genes to develop this disease, should be considered more. Early detection of mutation carriers in these genes, in turn, can play an important role in its prevention. Because this disease has a high prevalence in half of the global population, female screening of reported mutations in predisposing genes, which have been seen in breast cancer patients, seems necessary. In this review, a number of mutations in two predisposing genes (BRCA1 and BRCA2) that occurred in patients with a family history was investigated. We studied published articles about mutations in genes predisposed to breast cancer between 2000 and 2015. We then summarized and classified reported mutations in these two genes to recommend some exons which have a high potential to mutate. According to previous studies, exons have been reported as most mutated exons presented in this article. Considering the large size and high cost of screening all exons in these two genes in patients with a family history, especially in developing countries, the results of this review article can be beneficial and helpful in the selection of exon to screen for patients with this disease.
Menstrual CyclePMS Diagnosis and TreatmentPMDD ManagementLuteal Phase Symptoms
Premenstrual disorders affect up to 12% of women. The subspecialties of psychiatry and gynecology have developed overlapping but distinct diagnoses that qualify as a premenstrual disorder; these include premenstrual syndrome and premenstrual dysphoric disorder. These conditions encompass psychological and physical symptoms that cause significant impairment during the luteal phase of the menstrual cycle, but resolve shortly after menstruation. Patientdirected prospective recording of symptoms is helpful to establish the cyclical nature of symptoms that differentiate premenstrual syndrome and premenstrual dysphoric disorder from other psychiatric and physical disorders. Physicians should tailor therapy to achieve the greatest functional improvement possible for their patients. Select serotonergic antidepressants are first-line treatments. They can be used continuously or only during the luteal phase. Oral contraceptives and calcium supplements may also be used. There is insufficient evidence to recommend treatment with vitamin D, herbal remedies, or acupuncture, but there are data to suggest benefit from cognitive behavior therapy.
Although a fragility fracture family history (FFFH+) has repeatedly been shown to be associated with lower bone mineral density (BMD), its relationship to human BMD change is unclear. Animal research, however, documented that different purebred strains within rodent species have wide ranges in rates of bone acquisition during growth as well as in change post-ovariectomy. Our objective was to compare the rate of premenopausal spinal trabecular BMD change between women with and without a general family history of fragility fracture. Participants and methodsHealthy premenopausal community women participated in prospective observational studies at two academic Vancouver, Canada (n = 66) and Munich, Germany (n = 20). The primary outcome was annual spinal BMD change, measured by quantitative computed tomography (QCT). The two studies employed similar methodologies for assessing QCT and FFFH. Volunteer community participants had a mean age of 36.0 (SD, 6.9) years, body mass index 22.5 (2.4) and baseline QCT of 150.2 (22.5) mg/cm3 trabecular bone. The rates of BMD change - 3.5 (5.1)/year Vancouver, - 2.0 (3.4)/year Munich (95 % - 3.9, 0.9). Over a third of the women (31 of the 86, 36 %) reported FFFH+. Those with and without a FFFH were similar in demographics, nutrition, exercise, menstrual cycle and luteal phase lengths and physiological measures (serum calcium, osteocalcin and estradiol). However, women with FFFH+ lost FFFH+, - 4.9 (5.0), FFFH-, - 2.2 (4.4) mg/cm3/year (95 % CI diff - 0.7 to - 4.8, F1.83 = 7.88, p = 0.006). FFFH+ explained 7.7 % of the variance in QCT volumetric trabecular spinal bone change/year in these healthy premenopausal women. This study shows for the first time that having a history of a fragility fracture in a family member is associated with a greater rate of premenopausal spinal trabecular bone loss.
Is sexual and/or physical abuse history associated with incident endometriosis diagnosis or other gynecologic disorders among premenopausal women undergoing diagnostic and/or therapeutic laparoscopy or laparotomy regardless of clinical indication? No association was observed between either a history of sexual or physical abuse and risk of endometriosis, ovarian cysts or fibroids; however, a history of physical abuse was associated with a higher likelihood of adhesions after taking into account important confounding and mediating factors. Sexual and physical abuse may alter neuroendocrine-immune processes leading to a higher risk for endometriosis and other noninfectious gynecologic disorders, but few studies have assessed abuse history prior to diagnosis. STUDY DESIGN, SIZE, The study population for these analyses includes the ENDO Study (2007-2009) 473 women, ages 18-44 years, who underwent a diagnostic and/or therapeutic laparoscopy or laparotomy at 1 of the 14 surgical centers located in Salt Lake City, UT, USA or San Francisco, CA, USA. Women with a history of surgically confirmed endometriosis were excluded. PARTICIPANTS/MATERIALS, Prior to surgery, women completed standardized abuse questionnaires. Relative risk (RR) of incident endometriosis, uterine fibroids, adhesions or ovarian cysts by abuse history were estimated, adjusting for age, race/ethnicity, education, marital status, smoking, gravidity and recruitment site. We assessed whether a history of chronic pelvic pain, depression, or STIs explained any relationships via mediation analyses. Main 43 and 39% of women reported experiencing sexual and physical abuse. No association was observed between either a history of sexual or physical abuse, versus no history, and risk of endometriosis (aRR: 1.00 [95% confidence interval (CI): 0.80-1.25]); 0.83 [95% CI: 0.65-1.06]), ovarian cysts (aRR: 0.67 [95% CI: 0.39-1.15]); 0.60 [95% CI: 0.34-1.09]) or fibroids (aRR: 1.25 [95% CI: 0.85-1.83]); 1.36 [95% CI: 0.92-2.01]). Conversely, a history of physical abuse, versus no history, was associated with higher risk of adhesions (aRR: 2.39 [95% CI: 1.18-4.85]). We found no indication that the effect of abuse on women's adhesion risk could be explained by a history of chronic pelvic pain, depression or STIs. LIMITATIONS, Limitations to our study include inquiries on childhood physical but not sexual abuse. Additionally, we did not inquire about childhood or adulthood emotional support systems, found to buffer the negative impact of stress on gynecologic health. Abuse may be associated with some but not all gynecologic disorders with neuroendocrine-inflammatory origin. High prevalence of abuse reporting supports the need for care providers to screen for abuse and initiate appropriate follow-up. Supported by the Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts NO1-DK-6-3428, NO1-DK-6-3427, and 10001406-02). The authors have no potential competing interests.
Purdue-Smithe AC et al., 2016·The American journal of clinical nutrition
Clinically significant premenstrual syndrome (PMS) affects 15-20% of premenopausal women, substantially reducing quality of life. Women with PMS often are counseled to minimize caffeine intake, although only limited evidence supports this recommendation. We evaluated the association between total caffeine, coffee, and tea intake and the development of PMS in a case-control study nested within the prospective Nurses' Health Study II. All participants were free from PMS at baseline (1991). PMS cases reported a new clinician-made diagnosis of PMS on biennial questionnaires between 1993 and 2005, and then confirmed symptom timing and moderate-to-severe impact and severity of symptoms with the use of a retrospective questionnaire (n = 1234). Controls did not report PMS and confirmed experiencing no symptoms or few mild symptoms with limited personal impact (n = 2426). Caffeine, coffee, and tea intake was measured by food-frequency questionnaires every 4 y, and data on smoking, body weight, and other factors were updated every 2-4 y. Logistic regression was used to evaluate the associations of total caffeine intake and frequency of coffee and tea consumption with PMS. After adjustment for age, smoking, and other factors, total caffeine intake was not associated with PMS. The OR comparing women with the highest (quintile median = 543 mg/d) to the lowest (quintile median = 18 mg/d) caffeine intake was 0.79 (95% CI: 0.61, 1.04; P-trend = 0.31). High caffeinated coffee intake also was not associated with risk of PMS or specific symptoms, including breast tenderness (OR for ≥4 cups/d compared with <1/mo: 0.73; 95% CI: 0.48, 1.12; P-trend = 0.44). Our findings suggest that caffeine intake is not associated with PMS, and that current recommendations for women to reduce caffeine intake may not help prevent the development of PMS.
Bone HealthDMPA and Fracture RiskInjectable Contraceptives Side EffectsHypoestrogenism and Bone Loss
There has been concerning about women receiving depot medroxyprogesterone acetate (DMPA) contraception because of the prolonged hypoestrogenemic state regarding the potential negative effects on bone health. This study showed that DMPA exposure is associated with increased fracture risk and that fracture risk increases with longer DMPA exposure.
DMPA has been associated with impaired bone mineral acquisition during adolescence and accelerated bone loss in later life. We performed this large population-based study to assess the association between use of DMPA or combined oral contraceptives and the incident risk of fracture. We identified 4189 women between 20 and 44 years of age with a first-time fracture diagnosis, matched them with 4189 random controls using the Disease Analyzer database and investigated the relation with DMPA exposure. Overall, 11 % of the fracture cases and 7.7 % of the controls had DMPA use recorded. The adjusted OR for developing a fracture in patients with current use of DMPA compared to non-users was 0.97 (95 % CI 0.51-1.86), 2.41 (95 % CI 1.42-4.08), and 1.46 (95 % CI 0.96-2.23) for 1-2, 3-9, and ≥10 prescriptions, respectively. The adjusted OR for developing a fracture in patients with past use of DMPA compared to non-users was 0.96 (95 % CI 0.73-1.26), 1.14 (95 % CI 0.86-1.51), and 1.55 (95 % CI 1.07-2.27) for 1-2, 3-9, and ≥10 prescriptions, respectively. The highest fracture risk was identified in young patients less than 30 years with longer DMPA exposure (≥10 prescriptions; OR 3.04, 95 % CI 1.36-6.81), as well as in patients in the late reproductive years with past use of DMPA (OR 1.72, 95 % CI 1.13-2.63). Our results indicate that DMPA exposure is associated with increased fracture risk and may have negative effects on bone metabolism, resulting in impaired bone mineral acquisition during adolescence and accelerated bone loss in adult life.