Our recent study showed a dose-response relationship between environmental tobacco smoke (ETS) and the risk of early pregnancy loss. Smoking is known to affect female reproductive hormones. We explored whether ETS affects reproductive hormone profiles as characterized by urinary pregnanediol-3-glucuronide (PdG) and estrone conjugate (E1C) levels. We prospectively studied 371 healthy newly married nonsmoking women in China who intended to conceive and had stopped contraception. Daily records of vaginal bleeding, active and passive cigarette smoking, and daily first-morning urine specimens were collected for up to 1 year or until a clinical pregnancy was achieved. We determined the day of ovulation for each menstrual cycle. The effects of ETS exposure on daily urinary PdG and E1C levels in a +/-10 day window around the day of ovulation were analyzed for conception and nonconception cycles, respectively. Our analysis included 344 nonconception cycles and 329 conception cycles. In nonconception cycles, cycles with ETS exposure had significantly lower urinary E1C levels (beta = -0.43, SE = 0.08, p < 0.001 in log scale) compared with the cycles without ETS exposure. There was no significant difference in urinary PdG levels in cycles having ETS exposure (beta = -0.07, SE = 0.15, p = 0.637 in log scale) compared with no ETS exposure. Among conception cycles, there were no significant differences in E1C and PdG levels between ETS exposure and nonexposure. In conclusion, ETS exposure was associated with significantly lower urinary E1C levels among nonconception cycles, suggesting that the adverse reproductive effect of ETS may act partly through its antiestrogen effects.
Labad J et al., 2005·The Journal of clinical psychiatry
The aim of our study was to assess whether there is a relationship between reproductive cycle events and the initiation or changes in symptoms of obsessive-compulsive disorder (OCD). Forty-six female outpatients meeting DSM-IV criteria for OCD completed a semistructured interview at our OCD unit to assess the relationship between reproductive cycle events and OCD. Dates of data collection were from January 2001 to December 2003. In our sample, OCD onset occurred in the same year as menarche in 22% (N = 10), at pregnancy in 2% (N = 1), at postpartum in 7% (N = 3), and at menopause in 2% (N = 1). Worsening of preexisting OCD was reported by 20% of patients (9/45) at premenstruum, 8% (1/12) at pregnancy, 50% (6/12) at postpartum, and 8% (1/12) at menopause. The number of premenstrual mood symptoms, which included anxiety, irritability, mood lability and depressed mood, was associated with both premenstrual worsening of OCD (OR = 5.1, p < .01) and onset or worsening of OCD at postpartum (OR = 2.7, p < .05). Patients with an onset or worsening of OCD at postpartum also more frequently reported pre-menstrual worsening of OCD and previous history of major depressive disorder, including postpartum depression (p < or =.05 for all). In a substantial number of patients, the onset or worsening of OCD was related to reproductive cycle events, especially at menarche and postpartum. Certain women with OCD seem to be vulnerable to worsening of OCD at different reproductive periods that imply hormonal fluctuations, and premenstruum and post-partum were the 2 reproductive events with a greater vulnerability. Those patients whose OCD symptoms appeared to be related to reproductive events also exhibited a greater history of mood symptoms (premenstrual depression and major depressive episodes).
Milne RL et al., 2005·Cancer Epidemiol Biomarkers Prev
Recent oral contraceptive use has been associated with a small increase in breast cancer risk and a substantial decrease in ovarian cancer risk. The effects on risks for women with germ line mutations in BRCA1 or BRCA2 are unclear. Subjects were population-based samples of Caucasian women that comprised 1,156 incident cases of invasive breast cancer diagnosed before age 40 (including 47 BRCA1 and 36 BRCA2 mutation carriers) and 815 controls from the San Francisco Bay area, California, Ontario, Canada, and Melbourne and Sydney, Australia. Relative risks by carrier status were estimated using unconditional logistic regression, comparing oral contraceptive use in case groups defined by mutation status with that in controls. After adjustment for potential confounders, oral contraceptive use for at least 12 months was associated with decreased breast cancer risk for BRCA1 mutation carriers [odds ratio (OR), 0.22; 95% confidence interval (CI), 0.10-0.49; P < 0.001], but not for BRCA2 mutation carriers (OR, 1.02; 95% CI, 0.34-3.09) or noncarriers (OR, 0.93; 95% CI, 0.69-1.24). First use during or before 1975 was associated with increased risk for noncarriers (OR, 1.52 per year of use before 1976; 95% CI, 1.22-1.91; P < 0.001). There was no evidence that use of current low-dose oral contraceptive formulations increases risk of early-onset breast cancer for mutation carriers, and there may be a reduced risk for BRCA1 mutation carriers. Because current formulations of oral contraceptives may reduce, or at least not exacerbate, ovarian cancer risk for mutation carriers, they should not be contraindicated for a woman with a germ line mutation in BRCA1 or BRCA2.
Body LiteracyAdolescent ProgramsTeenSTAR ProgramSchool-Based Interventions
To evaluate the efficacy of an abstinence-centered sex education program in adolescent pregnancy prevention, the TeenSTAR Program was applied in a high school in Santiago, Chile. A total of 1259 girls from a Santiago high school were divided into three cohorts depending on the the 1996 cohort of 425 students, which received no intervention; the 1997 cohort, in which 210 students received an intervention and 213 (control group) did not; and the 1998 cohort, in which 328 students received an intervention and 83 (control group) did not. Students were randomly assigned to control and intervention groups in these cohorts, before starting with the program. We conducted a prospective, randomized study using the application of the TeenSTAR sex education program during the first year of high school to the intervention groups in the 1997 and 1998 cohorts. All cohorts were followed up for 4 years; pregnancy rates were recorded and subsequently contrasted in the intervention and control groups. Pregnancy rates were measured and Risk Ratio with 95% confidence interval were calculated for intervention and control groups in each cohort. Pregnancy rates for the intervention and control groups in the 1997 cohort were 3.3% and 18.9%, respectively (RR: 0.176, CI: 0.076-0.408). Pregnancy rates for the intervention and control groups in the 1998 cohort were 4.4% and 22.6%, respectively (RR 0.195, CI: 0.099-0.384). The abstinence-centered TeenSTAR sex education intervention was effective in the prevention of unintended adolescent pregnancy.
To analyze IVF outcomes in patients with a history of one or more elevations in basal FSH who have a normal basal FSH at the start of their IVF cycle, compared with the general IVF population.
Retrospective clinical study.
University hospital. PATIENT(S): General IVF patient population. INTERVENTION(S): Patients received standard IVF gonadotropin protocols, oocyte retrieval, and embryo transfer. MAIN OUTCOME MEASURE(S): Oocyte yield, fertilization, implantation, clinical pregnancy, and cancellation rate. RESULT(S): Oocyte yields were lower in patients with a history of elevated basal FSH, for all age groups, and showed an age-dependent decline in all patients. Over the age of 40 years, both implantation and clinical pregnancy rates were lower in these patients, with no significant difference observed in patients under the age of 40 years. No pregnancies were observed in patients with a history of three or more elevated FSH levels, regardless of age. CONCLUSION(S): A history of elevated basal FSH levels in patients under the age of 40 years predicts a lower oocyte yield in IVF cycles with normal basal FSH levels but does not translate to either lower pregnancy or implantation rates. Patients aged >40 years with prior elevations in basal FSH levels have both compromised ovarian response and compromised embryo quality relative to those with normal FSH levels, as illustrated by lower oocyte yield, higher cancellation rates, and lower implantation and pregnancy rates.
Calendar-based methods are not usually considered effective or useful methods of family planning among health professionals. However, new "high-" and "low"-tech calendar methods have been developed, which are easy to teach, to use, and may be useful in helping couples avoid pregnancy. The low-tech models are based on a fixed-day calendar system. The high-tech models are based on monitoring urinary metabolites of female reproductive hormones. Both systems have high levels of satisfaction. This article describes these new models of family planning and the research on their effectiveness. The author proposes a new algorithm for determining the fertile phase of the menstrual cycle for either achieving or avoiding pregnancy.
Contraception/ComparisonNational TrendsUtilization PatternsNational Survey of Family Growth
This report presents national estimates of contraceptive use and method choice based on the 1982, 1995, and 2002 National Surveys of Family Growth (NSFG). It also presents data on where women obtained family planning and medical services, and some of the services that they received. Data were collected through in-person interviews with 12,571 men and women 15-44 years of age in the civilian noninstitutional population of the United States in 2002. This report is based on the sample of 7,643 women interviewed in 2002. The response rate for women in the study was about 80 percent. The leading method of contraception in the United States in 2002 was the oral contraceptive pill, used by 11.6 million women; the second leading method was female sterilization, used by 10.3 million women. The condom was the third-leading method, used by about 9 million women and their partners. The condom is the leading method at first intercourse; the pill is the leading method among women under 30; and female sterilization is the leading method among women 35 and older. More than 98 percent of women 15-44 years of age who have ever had sexual intercourse with a male (referred to as "sexually experienced women") have used at least one contraceptive method. Over the 20 years from 1982 to 2002, the percent who had ever had a partner who used the male condom increased from 52 to 90 percent. The proportion who had ever had a partner who used withdrawal increased from 25 percent in 1982 to 56 percent in 2002. Another important measure of contraceptive use is use at the before 1980, only 43 percent of women (or their partner) used a method of birth control at their first premarital intercourse. By 1999-2002, the proportion using a method at first premarital intercourse had risen to 79 percent.
Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2004. 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).
Large retrospective cohort study investigating whether different causes of infertility (endometriosis, anovulation, tubal disease, male factor, cervical/uterine disorders) predict future cancer risk among 12,193 women who sought infertility treatment at five U.S. reproductive endocrinology practices between 1965 and 1988, with cancer incidence tracked through 1999.
For many years, individual women and doctors have experimented with extending the duration of active oral contraceptive (OC) pills between pill-free intervals (long OC) to control menstruation. The U.S. approval of an OC with 84 active days and 7 pill-free days in 2003 has attracted considerable media attention. In this review we consider the published evidence on the effectiveness, side effects, and risks of menstrual suppression with long OC. We performed a systematic review of published literature on long OC, up to April 2003. Ten papers were located; two were randomized trials comparing long OC to standard OC; the remaining studies were single-group observational studies. Women on long OC schedules had fewer days of scheduled bleeding during days without pills but more days of unscheduled bleeding and spotting than those on standard OC. These problems were worse for women new to OC and diminished over time. Women on long OC were more likely to discontinue due to poor control of bleeding; women on standard OC were more likely to stop because of problems with headaches. Women on long OC and standard OC both showed increases in physiological factors related to clotting, with a nonsignificant tendency for those on long OC to be more affected. No studies considered the effects of long OC on breast tissue, breast density, endometrial safety, or adolescent maturation and reproductive development. No systematic data were available on the return to reproductive function and fertility after taking long OC. There were no placebo-controlled trials and no information on how long OC compares to normal, unmedicated menstrual cycles. Therefore we believe scientific evidence for safety of long OC use is presently lacking.
Wade GN et al., 2004·American journal of physiology. Regulatory, integrative and comparative physiology
Natural selection has linked the physiological controls of energy balance and fertility such that reproduction is deferred during lean times, particularly in female mammals. In this way, an energetically costly process is confined to periods when sufficient food is available to support pregnancy and lactation. Even in the face of abundance, nutritional infertility ensues if energy intake fails to keep pace with expenditure. A working hypothesis is proposed in which any activity or condition that limits the availability of oxidizable fuels (e.g., undereating, excessive energy expenditure, diabetes mellitus) can inhibit both gonadotropin-releasing hormone (GnRH)/luteinizing hormone secretion and female copulatory behaviors. Decreases in metabolic fuel availability appear to be detected by cells in the caudal hindbrain. Hindbrain neurons producing neuropeptide Y (NPY) and catecholamines (CA) then project to the forebrain where they contact GnRH neurons both directly and also indirectly via corticotropin-releasing hormone (CRH) neurons to inhibit GnRH secretion. In the case of estrous behavior, the best available evidence suggests that the inhibitory NPY/CA system acts primarily via CRH or urocortin projections to various forebrain loci that control sexual receptivity. Disruption of these signaling processes allows normal reproduction to proceed in the face of energetic deficits, indicating that the circuitry responds to energy deficits and that no signal is necessary to indicate that there is an adequate energy supply. While there is a large body of evidence to support this hypothesis, the data do not exclude nutritional inhibition of reproduction by other pathways and processes, and the full story will undoubtedly be more complex than this.
EndometriosisGenetics and Immune MechanismsPain and InfertilityCancer and Autoimmune Risk
Endometriosis is an oestrogen-dependent disorder that can result in substantial morbidity, including pelvic pain, multiple operations, and infertility. New findings on the genetics, the possible roles of the environment and the immune system, and intrinsic abnormalities in the endometrium of affected women and secreted products of endometriotic lesions have given insight into the pathogenesis of this disorder and serve as the background for new treatments for disease-associated pain and infertility. Affected women are at higher risk than the general female population of developing ovarian cancer, and they also may be at increased risk of breast and other cancers as well as autoimmune and atopic disorders. Clinicians should assess and follow up affected women for these and other associated disorders. There will probably be a new repertoire of approaches for treatment and perhaps cure of this enigmatic disorder in the near future.
Bone HealthFamily History and GeneticsMeta-AnalysisProspective Cohort Studies
The aims of the present study were to determine whether a parental history of any fracture or hip fracture specifically are significant risk factors for future fracture in an international setting, and to explore the effects of age, sex and bone mineral density (BMD) on this risk. We studied 34,928 men and women from seven prospectively studied cohorts followed for 134,374 person-years. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, DOES and cohorts at Sheffield, Rochester and Gothenburg. The effect of family history of osteoporotic fracture or of hip fracture in first-degree relatives, BMD and age on all clinical fracture, osteoporotic fracture and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted beta coefficients. A parental history of fracture was associated with a modest but significantly increased risk of any fracture, osteoporotic fracture and hip fracture in men and women combined. The risk ratio (RR) for any fracture was 1.17 (95% CI=1.07-1.28), for any osteoporotic fracture was 1.18 (95% CI=1.06-1.31), and for hip fracture was 1.49 (95% CI=1.17-1.89). The risk ratio was higher at younger ages but not significantly so. No significant difference in risk was seen between men and women with a parental history for any fracture (RR=1.17 and 1.17, respectively) or for an osteoporotic fracture (RR=1.17 and 1.18, respectively). For hip fracture, the risk ratios were somewhat higher, but not significantly higher, in men than in women (RR=2.02 and 1.38, respectively). A family history of hip fracture in parents was associated with a significant risk both of all osteoporotic fracture (RR 1.54; 95CI=1.25-1.88) and of hip fracture (RR=2.27; 95% CI=1.47-3.49). The risk was not significantly changed when BMD was added to the model. We conclude that a parental history of fracture (particularly a family history of hip fracture) confers an increased risk of fracture that is independent of BMD. Its identification on an international basis supports the use of this risk factor in case-finding strategies.
Bone HealthD2 vs D3 PotencyPharmacokinetic StudiesVitamin D Supplementation
Vitamins D(2) and D(3) are generally considered to be equivalent in humans. Nevertheless, physicians commonly report equivocal responses to seemingly large doses of the only high-dose calciferol (vitamin D(2)) available in the U.S. market. The relative potencies of vitamins D(2) and D(3) were evaluated by administering single doses of 50,000 IU of the respective calciferols to 20 healthy male volunteers, following the time course of serum vitamin D and 25-hydroxyvitamin D (25OHD) over a period of 28 d and measuring the area under the curve of the rise in 25OHD above baseline. The two calciferols produced similar rises in serum concentration of the administered vitamin, indicating equivalent absorption. Both produced similar initial rises in serum 25OHD over the first 3 d, but 25OHD continued to rise in the D(3)-treated subjects, peaking at 14 d, whereas serum 25OHD fell rapidly in the D(2)-treated subjects and was not different from baseline at 14 d. Area under the curve (AUC) to d 28 was 60.2 ng.d/ml (150.5 nmol.d/liter) for vitamin D(2) and 204.7 (511.8) for vitamin D(3) (P < 0.002). Calculated AUC(infinity) indicated an even greater differential, with the relative potencies for D(3):D(2) being 9.5:1. Vitamin D(2) potency is less than one third that of vitamin D(3). Physicians resorting to use of vitamin D(2) should be aware of its markedly lower potency and shorter duration of action relative to vitamin D(3).
Utilizing data from the Canadian Multicentre Osteoporosis Study (CaMos), we examined the association between potential risk factors and incident vertebral and nonvertebral fractures. A total of 5,143 postmenopausal women were enrolled. Information collected during the study included data from the CaMos baseline and annually mailed fracture questionnaires, the Short Form 36 (SF-36), the Health Utilities Index, and physical measurements. Participants were followed for 3 years. Postmenopausal women were classified into four groups according to their incident those without a new fracture; those with a new clinically recognized vertebral fracture; those with an incident nonvertebral fracture at the wrist, hip, humerus, pelvis, or ribs (main nonvertebral fracture group); and those with any new nonvertebral fracture (any-nonvertebral-fracture group). We performed multivariate Cox proportional hazard analysis using all possible risk factors to determine the association between risk factors and the time to the first minimal trauma fracture. Best predictive models were also determined using variables that were included in the full models. The Bayesian information criterion was used for model selection. For all analyses, relative risks and associated 95% confidence intervals were calculated. During the follow-up period, 34, 163, and 280 women developed a vertebral, a main nonvertebral, or any nonvertebral fracture, respectively. The best predictive models indicated that a five point lower quality of life as measured by the SF-36 physical component summary score was associated with relative risks of 1.21 (95% CI, 1.02 to 1.44), 1.17 (95% CI, 1.07 to 1.28), and 1.19 (95% CI, 1.11 to 1.27) for incident vertebral, main nonvertebral, and all nonvertebral fractures, respectively. In addition, for a one standard deviation (SD=0.12) lower femoral neck BMD, the relative risks for incident vertebral, main nonvertebral, and any nonvertebral fractures increased by 2.73 (95% CI, 1.74 to 4.28), 1.39 (95% CI, 1.06 to 1.82), and 1.34 (95% CI, 1.09 to 1.65), respectively. Furthermore, various anthropometric measures, disease conditions, and medications are associated with a new fracture. Identifying postmenopausal women at risk is important given that fracture prevention therapies are now available.
"Fertility awareness-based methods" (FAB) of family planning "involve identification of the fertile days of the menstrual cycle, whether by observing fertility signs such as cervical secretions and basal body temperature, or by monitoring cycle days. FAB methods can be used in combination with abstinence or barrier methods during the fertile time" (WHO 2000). Several names have been used to describe this approach to contraception, including "rhythm," "natural family planning" and "periodic abstinence." Fertility awareness-based methods can be used with abstinence from sexual intercourse. Alternatively, they can be used with barrier contraceptives or withdrawal during presumed fertile times. We retrieved and analyzed all randomized controlled trials that examined any fertility awareness-based methods used for contraception. We searched the computerized databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, POPLINE, EMBASE, and LILACS (each from its inception to January, 2004) for randomized controlled trials of fertility awareness-based methods. We examined the reference list of each trial as well as that of review articles.
We included all randomized controlled trials in any language that compared any fertility awareness-based methods for contraception with a placebo; another method, including an alternative fertility awareness-based method; or fertility awareness-based methods used in conjunction with another contraceptive. We assessed all titles and abstracts found for inclusion. We evaluated the methodological quality of the trials for potential biases by qualitatively assessing the study design; randomization method; allocation concealment; blinding; premature discontinuation rates; and loss to follow-up rates. Because of methodological weaknesses, we could not enter the trial results in RevMan, calculate measures of association, or aggregate data. Because of poor methods and reporting, pregnancy rates could not be determined. A trial in Colombia found similar numbers of pregnancies among women randomized to the ovulation and symptothermal methods. In contrast, a companion trial in Los Angeles observed more pregnancies in the group assigned to the ovulation method. In the two U.S. trials, recruitment of participants was unexpectedly difficult; this aspect was not mentioned in the report from Colombia. Continuation rates were poor. In the two larger trials, most participants discontinued their assigned method before entering the observation phase of the trial. REVIEWERS' The comparative efficacy of fertility awareness-based methods of contraception remains unknown. Despite intensive training and ongoing support, most participants in these trials discontinued prematurely. Contraceptive methods should be properly evaluated, preferably in randomized controlled trials, before adoption and dissemination.
To test the efficacy of the TwoDay Method, a new fertility awareness-based method of family planning that provides women with simple instructions to identify the days each cycle when they are most likely to become pregnant. Users avoid unprotected intercourse on days when cervical secretions are present on that day or on the day before, to prevent pregnancy.
Prospective, nonrandomized, multicenter study.
Five culturally diverse sites in Guatemala, Peru, and the Philippines. PATIENT(S): Four hundred fifty women, aged 18-39 years, wishing to use a fertility awareness-based method to prevent or delay pregnancy. INTERVENTION(S): Study participants were followed for up to 13 cycles of method use. MAIN OUTCOME MEASURE(S): Life table pregnancy rate. RESULT(S): The first-year pregnancy rate was 3.5 (pregnancies per 100 women/years) with correct use of the method (pregnancies and cycles with no intercourse on identified fertile days), 6.3 with use of a backup method on the fertile days, and 13.7 including all cycles and all pregnancies in the analysis. CONCLUSION(S): The TwoDay Method offers a valuable addition to the services that reproductive health and other programs can offer. Its efficacy compares well with that of other coitus-dependent family-planning methods; it is easy to teach, learn, and use; and it can address the need of women for simple, accurate instructions for identifying their fertile days.
The rise in FSH (FSHr) that leads to the recruitment of a cohort of follicles during the menstrual cycle occurs during the luteal-follicular transition, however, it is unclear whether it consistently occurs on one particular day, or is subjected to reproductive ageing. We determined the FSHr in 836 complete menstrual cycles from 102 women with regular menses using an algorithm, and additionally compared the relative variation in FSH during the last 14 days of the cycle. Possible effects of reproductive ageing on the onset of FSHr were also investigated. The day of FSHr follows a normal distribution with a median value of -4 (relative to first day of menses), mean -4.1 and SD 2.1. Analysis of the relative changes in FSH during the last 14 days of the cycle revealed the first significant rise on day -4 (P=0.0033), coinciding with the first significant drop in estrogens (P=0.0002). No effect of chronological age, or initial FSH levels, on FSHr was found, however, there was an inverse relationship between total follicular phase length (from day of FSHr to LH peak) and initial FSH levels (P<0.0001). The initial FSH rise in the cycle occurs consistently 4 days before menses, is related to a drop in estrogen levels, and is not affected by reproductive ageing.
InfertilityDepression and AnxietyMental Health ScreeningPsychiatric Comorbidity
Chen TH et al., 2004·Human reproduction (Oxford, England)
Little is known about the prevalence of specific depressive and anxiety disorders in women before a new course of assisted reproductive technology treatment. Few studies have adopted the proper psychiatric diagnostic procedures.
All consecutive women visiting the assisted reproduction clinic of a university-affiliated medical centre, with the intention of starting a new assisted reproduction treatment course, were recruited. A psychiatrist made a diagnosis of psychiatric disorders using a structured interview, the Mini-International Neuropsychiatric Interview (MINI).
Of a total of 112 participants, 40.2% had a psychiatric disorder. The most common diagnosis was generalized anxiety disorder (23.2%), followed by major depressive disorder (17.0%), and dysthymic disorder (9.8%). Participants with a psychiatric morbidity did not differ from those without in terms of age, education, income, or years of infertility. Women with a history of previous assisted reproduction treatment did not differ from those without in depression or anxiety.
Depressive and anxiety disorders were highly prevalent among women who visited an assisted reproduction clinic for a new course of the treatment. Demographic features and a history of previous assisted reproduction treatment were not risk factors for these psychiatric morbidities in the assisted reproduction clinic.
Einarson A et al., 2004·BJOG : an international journal of obstetrics and gynaecology
Ondansetron (Zofran) is a drug used for the treatment of nausea and vomiting caused by cancer chemotherapy. Despite the fact that it is not indicated, women are being prescribed this drug for the treatment of nausea and vomiting of pregnancy (NVP). There is a paucity of information on fetal safety for this indication. The objective of this study is to determine whether this drug increases the baseline rate of major malformations. A prospective comparative observational study. Teratogen Information Services (TIS). Pregnant women. Our three groups included women who were exposed to ondansetron and women exposed to (1) other anti-emetics and (2) non-teratogen exposures. All of the women called either our NVP Helpline or TIS at The Motherisk Program in Toronto, Canada, or The Mothersafe Program in Sydney, Australia. Rates of major malformation. We have completed 176 pregnancy outcomes in each group. In the ondansetron cohort, there were 169 live births, 5 miscarriages, 2 therapeutic abortions, 6 (3.6%) major malformations and the mean birthweight was 3362 g [SD 525]. There were no statistical differences in any of the study endpoints between the ondansetron and the comparison groups. This drug does not appear (although the sample size is limited) to be associated with an increased risk for major malformations above baseline.
The SF-36 is widely used to assess health-related quality of life (HRQOL), but with few longitudinal studies in healthy populations, it is difficult to quantify its natural history. This is important because any measure of change following an intervention may be confounded by natural changes in HRQOL. This paper assesses mean changes in SF-36 scores over a 3-year period in men and women between the ages of 40 and 59 years at baseline. Subjects were randomly selected from nine Canadian cities. Mean SF-36 changes over a 3-year period (1996/1997-1999/2000) were calculated for each gender within 5-year age categories. Multiple imputation was used to correct for potential bias due to missing data. The baseline cohort included 1,974 women and 975 men between 40 and 59 years. Mean changes in HRQOL tended to be small. Women demonstrated small average declines in 22 of the 32 age and domain groupings (4 age groups, 8 SF-36 domains) while men showed declines in 14/32. Most participants stayed within 10 points of their original baseline score. Mean SF-36 scores change only slightly over three years in middle-aged Canadians, although there is much individual variation. It may be necessary to adjust for the natural evolution of SF-36 scores when interpreting results from longitudinal studies. Le SF-36 est un court questionnaire très utilisé pour évaluer la qualité de vie liée à la santé (HRQOL). Toutefois, vu le petit nombre d’études longitudinales menées auprès de populations en bonne santé, il est difficile d’évaluer l’histoire naturelle du SF-36, ce qui est important parce que tout changement noté résultant d’une intervention peut être confondu avec des changements normaux de la qualité de vie liée à la santé. Cet article évalue les changements moyens dans les scores des SF-36 sur une période de trois ans chez les hommes et les femmes qui étaient âgés de 40 à 59 ans lors de leur visite initiale. Méthode: Les sujets ont été choisis au hasard dans neuf villes canadiennes. Les changements moyens dans les résultats du SF-36 sur une période de trois ans (1996–1997 à 1999–2000) ont été calculés par sexe et par groupe d’âge de cinq ans. L’imputation multiple a été utilisée pour corriger tout biais résultant d’informations manquantes. Résultats: La cohorte initiale comportait 1 974 femmes et 975 hommes âgés de 40 à 59 ans. Les changements moyens étaient plutôt légers. Chez les femmes, 22 des 32 groupes d’âge et sous-échelles (quatre groupes d’âge, huit sous-échelles SF-36) présentaient de légères diminutions moyennes, alors que chez les hommes, ce nombre était de 14 groupes sur 32. Le score de la plupart des participants est demeuré en deçà de 10 points du score initial lors de l’entrée dans l’étude. Interprétation: Les scores moyens du SF-36 ne changent que légèrement sur une période de trois ans dans la population canadienne d’âge moyen. Toutefois, il pourrait s’avérer nécessaire de tenir compte de l’évolution naturelle des scores du SF-36 lors de l’interprétation des résultats d’études longitudinales.
Bone HealthPrevious Fracture HistoryInternational CohortsRisk Factor Quantification
Previous fracture is a well-documented risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex, and bone mineral density (BMD). We studied 15259 men and 44902 women from 11 cohorts comprising EVOS/EPOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and two cohorts from Gothenburg. Cohorts were followed for a total of 250000 person-years. The effect of a prior history of fracture on the risk of any fracture, any osteoporotic fracture, and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex, and BMD. The results of the different studies were merged by using the weighted beta-coefficients. A previous fracture history was associated with a significantly increased risk of any fracture compared with individuals without a prior fracture (RR = 1.86; 95% CI = 1.75-1.98). The risk ratio was similar for the outcome of osteoporotic fracture or for hip fracture. There was no significant difference in risk ratio between men and women. Risk ratio (RR) was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any fracture (8%) and for hip fracture (22%). The risk ratio was stable with age except in the case of hip fracture outcome where the risk ratio decreased significantly with age. We conclude that previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.
PregnancySelenium and MicronutrientsPreeclampsia and ToxemiaChemical Stress
Furthermore, direct questioning and a scrutiny of records of these patients showed that before the full development of the signs of toxaemia—that is, oedema, hypertension, and albuminuria—most had earlier in the pregnancy experienced a symptomatic stage characterized by relatively minor afflictions—for example, lethargy 43%, headache 48%, visual aura 37%, vertigo 29%, nausea and vomiting 16%, irritability 14%, depression 9%, and backache 6%. In fact, only 7% disclosed freedom from these symptoms during a toxaemic pregnancy.
General OB/GYNThyroid and Celiac AssociationAntigliadin and Thyroid AutoantibodiesAutoimmune Thyroiditis
To investigate the presence of the antigliadin antibodies in the patients with Graves' disease and Hashimoto's thyroiditis. Four hundred patients with autoimmune thyroid disease (280 Graves' disease and 120 Hashimoto's thyroiditis ) were included in the study. The patients with celiac sprue patients were excluded. For the diagnosis of autoimmune thyroiditis, blood levels of thyrotropin (TSH), free thyroxine (FT4), and the titration of thyroid autoantibodies (TgAb and TmAb) were measured, and the thyroid gland was ultrasonographycally evaluated. After the diagnosis of autoimmune thyroid disease was established, the titration of antigliadin antibodies (Ig A and B) were routinely detected. Twenty two patients (5.5 per cent) with autoimmune thyroiditis had positive antigliadin antibodies. Polyglandular endocrine syndrome was diagnosed in most of these patients. We claim that polyglandular endocrine syndrome is the commonest cause of positivity of antigliadin antibodies in the patients with autoimmune thyroid disease.
Shankar M et al., 2004·BJOG : an international journal of obstetrics and gynaecology
To determine the prevalence of von Willebrand disease in women presenting with menorrhagia. Systematic review of studies evaluating the prevalence of von Willebrand disease in women with menorrhagia. Hospital outpatient clinics (mainly gynaecological) and population surveys. Women presenting with menorrhagia. Relevant studies were extracted from MEDLINE search, bibliographies of identified articles and published proceedings of meetings and conferences. Number of women with von Willebrand disease. Eleven studies were included, totalling 988 women with menorrhagia. One hundred and thirty-one women were diagnosed to have von Willebrand disease with prevalences in individual studies ranging from 5% to 24%. The overall prevalence was 13% (95% CI 11-15.6%). The prevalence was higher in the European studies-18% (95% CI 15-23%) compared with that in North American studies-10% (95% CI 7.5-13%). This difference (P= 0.007) is likely to be the result of differences in the studies, which include method of recruitment of study population, method of assessing menstrual blood loss ethnic composition of study population, criteria for diagnosis and use of race- and ABO blood group-specific values for von Willebrand factor. The prevalence of von Willebrand disease is increased in women with menorrhagia and is the underlying cause in a small but significant group of women with menorrhagia across the world. Testing for this disorder should be considered when investigating women with menorrhagia, especially those of Caucasian origin, those with no obvious pelvic pathology or with additional bleeding symptoms.
Body LiteracyMenstrual Cycle AwarenessGynecologic ChartingMenstrual Cycle Charting
The goal of an integrative science of women's health is bringing together childbearing with women's health during the lifespan. Enhancing a woman's ability to conceive and maintain a pregnancy is influenced by decisions made well before the beginning of a pregnancy. Identifying ovulatory disorders makes it possible to intervene early in a young woman's childbearing years. Gynecologic charting typically used in natural family planning provides information to the woman and to the healthcare provider that is useful for diagnosis. If young women have a better understanding of fertility and menstrual cycle function, they are in a stronger position to make informed decisions about how they wish to manage their reproductive and sexual health. It may be possible to educate the young woman in health habits that will lead to a healthy pregnancy when she chooses and/or to treat the cause of the ovulatory disorder. This article focuses on polycystic ovary syndrome and hypothalamic dysfunction which can cause menstrual cycle abnormalities in which gynecologic charting is useful in young women.
To determine the efficacy of combined l-carnitine and l-acetyl-carnitine therapy in infertile males with oligo-astheno-teratozoospermia. Placebo-controlled double-blind randomized trial. University tertiary referral center. PATIENT(S): Sixty infertile patients (aged 20-40 years) with the following baseline concentration, 10 to 40 x 10(6)/mL; forward motility, <15%; total motility, 10% to 40%; and atypical forms, <80%. Fifty-six patients completed the study. INTERVENTION(S): Patients were submitted to a combined treatment of l-carnitine (2 g/d) and l-acetyl-carnitine (1 g/d) or of placebo; the study design was 2 months' wash-out, 6 months of therapy or of placebo, and 2 months' follow-up. MAIN OUTCOME MEASURE(S): Variation in the semen parameters that were used for patient selection. RESULT(S): Even though increases were seen in all sperm parameters after combined carnitine treatment, the most significant improvement in sperm motility (both forward and total) was present in patients who had lower initial absolute values of motile sperm (<4 x 10(6) forward or <5 x 10(6) total motile spermatozoa per ejaculate). CONCLUSION(S): Combined treatment with l-carnitine and l-acetyl-carnitine in a controlled study of efficacy was effective in increasing sperm motility, especially in groups with lower baseline levels.
Gynaecological laparotomies are associated with considerable adhesion-related burdens; however, few data are available concerning laparoscopic surgery. This study evaluated the epidemiology of adhesion-related readmissions following open and laparoscopic procedures. Records from 24,046 patients undergoing gynaecological surgery in Scottish National Health Service hospitals during 1996 were assessed retrospectively. Cohorts comprised 15,197 patients undergoing laparoscopic surgery and 8849 patients undergoing laparotomies. Adhesion-related readmission episodes (directly and possibly related) were assessed over 4 years following initial surgery and were expressed as percentages of the number of initial procedures. Directly adhesion-related readmissions 1 year after initial in the high-risk group (adhesiolysis and cyst drainage) 1.3%; medium-risk (therapeutic and diagnostic procedures not categorized as highor low-risk) 1.5%; and low-risk (Fallopian tube sterilizations) 0.2%. Readmissions for laparotomy following surgery on the Fallopian tubes were 0.9%, ovaries 2.1%, uterus 0.6% and vagina 0%. Readmissions occurred at reduced rates in the second, third and fourth years after surgery. Exclusion of patients who underwent surgery within the previous 5 years resulted in reduced readmission rates following laparotomy and high-risk laparoscopy. With the exception of laparoscopic sterilizations, open and laparoscopic gynaecological surgery are associated with comparable risks of adhesion-related readmissions.
Smoking is widely considered a risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex and bone mineral density (BMD). We studied 59,232 men and women (74% female) from ten prospective cohorts comprising EVOS/EPOS, DOES, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, Hiroshima and two cohorts from Gothenburg. Cohorts were followed for a total of 250,000 person-years. The effect of current or past smoking, on the risk of any fracture, any osteoporotic fracture and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex and BMD. The results of the different studies were merged using the weighted beta-coefficients. Current smoking was associated with a significantly increased risk of any fracture compared to non-smokers (RR=1.25; 95% Confidence Interval (CI)=1.15-1.36). Risk ratio (RR) was adjusted marginally downward when account was taken of BMD, but it remained significantly increased (RR=1.13). For an osteoporotic fracture, the risk was marginally higher (RR=1.29; 95% CI=1.13-1.28). The highest risk was observed for hip fracture (RR=1.84; 95% CI=1.52-2.22), but this was also somewhat lower after adjustment for BMD (RR=1.60; 95% CI=1.27-2.02). Risk ratios were significantly higher in men than in women for all fractures and for osteoporotic fractures, but not for hip fracture. Low BMD accounted for only 23% of the smoking-related risk of hip fracture. Adjustment for body mass index had a small downward effect on risk for all fracture outcomes. For osteoporotic fracture, the risk ratio increased with age, but decreased with age for hip fracture. A smoking history was associated with a significantly increased risk of fracture compared with individuals with no smoking history, but the risk ratios were lower than for current smoking. We conclude that a history of smoking results in fracture risk that is substantially greater than that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.
The relationship between use of corticosteroids and fracture risk was estimated in a meta-analysis of data from seven cohort studies of approximately 42,000 men and women. Current and past use of corticosteroids was an important predictor of fracture risk that was independent of prior fracture and BMD.
The aims of this study were to validate that corticosteroid use is a significant risk factor for fracture in an international setting and to explore the effects of age and sex on this risk. We studied 42,500 men and women from seven prospectively studied cohorts followed for 176,000 patient-years. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, Dubbo Osteoporosis Epidemiology Study (DOES), and prospective cohorts at Sheffield, Rochester, and Gothenburg. The effect of ever use of corticosteroids, BMD, age, and sex on all fracture, osteoporotic fracture, and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted beta coefficients. Previous corticosteroid use was associated with a significantly increased risk of any fracture, osteoporotic fracture, and hip fracture when adjusted for BMD. Relative risk of any fracture ranged from 1.98 at the age of 50 years to 1.66 at the age of 85 years. For osteoporotic fracture, the range of relative risk was 2.63-1.71, and for hip fracture 4.42-2.48. The estimate of relative risk was higher at younger ages, but not significantly so. No significant difference in risk was seen between men and women. The risk was marginally and not significantly upwardly adjusted when BMD was excluded from the model. The risk was independent of prior fracture. In the three cohorts that documented current corticosteroid use, BMD was significantly reduced at the femoral neck, but fracture risk was still only partly explained by BMD. We conclude that prior and current exposure to corticosteroids confers an increased risk of fracture that is of substantial importance beyond that explained by the measurement of BMD. Its identification on an international basis validates the use of this risk factor in case-finding strategies.
Since the introduction of hormonal contraceptives in the 1960s, there have been a variety of both health benefits and safety concerns attributed to their use. In most instances, the noncontraceptive benefits of oral contraceptives (OCs) outweigh the potential cardiovascular risks. In fact, the probability of a patient experiencing a cardiovascular event while taking a low-dose OC is very low. However, smoking, hypertension, obesity, and diabetes are risk factors that must be taken into account when prescribing OCs. The neoplastic effects of hormonal contraceptives have been extensively studied, and recent meta-analyses indicate that there is a reduction in the risk of endometrial and ovarian cancer, a possible small increase in the risk for breast and cervical cancer, and an increased risk of liver cancer. Finally, many women will experience noncontraceptive health benefits with OCs that expand far beyond pregnancy prevention. Some of these benefits include reduction in menstrual-related symptoms, fewer ectopic pregnancies, a possible increase in bone density, and possible protection against pelvic inflammatory disease.
The new third generation aromatase inhibitors are extremely potent and specific oral inhibitors of estrogen production. We reported the success of using aromatase inhibitors for induction of ovulation in World Health Organization (WHO) type II anovulatory patients. Promising pregnancy rates were associated with the use of aromatase inhibitors for induction of ovulation in these women. In addition, the use of aromatase inhibition in conjunction with gonadotropin injection was associated with a significant reduction in the gonadotropin dose required for optimum controlled ovarian hyperstimulation. We believe that these oral agents are efficient and safe and have many advantages compared with clomiphene citrate (CC). We propose that aromatase inhibitors will replace CC in the future as the new primary treatment for ovulation induction. In this review, we present an update on the use of aromatase inhibitors for induction of ovulation and we discuss several new areas of potential interest regarding the use of aromatase inhibitors, either alone or together with recombinant follicle-stimulating hormone (FSH) for infertility treatment. Further research in these areas may demonstrate an expanded role in assisted reproductive technologies.
Weiss JL et al., 2004·American journal of obstetrics and gynecology
This study was undertaken to determine whether obesity is associated with obstetric complications and cesarean delivery. A large prospective multicenter database was studied. Subjects were divided into 3 body mass index (BMI) less than 30 (control), 30 to 34.9 (obese), and 35 or greater (morbidly obese). Groups were compared by using univariate and multivariable logistic regression analyses. The study included 16,102 3,752 control, 1,473 obese, and 877 morbidly obese patients. Obesity and morbid obesity had a statistically significant association with gestational hypertension (odds ratios [ORs] 2.5 and 3.2), preeclampsia (ORs 1.6 and 3.3), gestational diabetes (ORs 2.6 and 4.0), and fetal birth weight greater than 4000 g (ORs 1.7 and 1.9) and greater than 4500 g (ORs 2.0 and 2.4). For nulliparous patients, the cesarean delivery rate was 20.7% for the control group, 33.8% for obese, and 47.4% for morbidly obese patients. Obesity is an independent risk factor for adverse obstetric outcome and is significantly associated with an increased cesarean delivery rate.
AndrologyTestosterone and MetabolismHormonal AssessmentSHBG and Insulin Resistance
Previous reports of an association between low testosterone levels and diabetes risk were often confounded by covariation of sex hormone-binding globulin (SHBG) and testosterone measurements. Measurements of bioavailable and free testosterone, more reliable indexes of biologically active testosterone, were examined for their associations with markers of insulin resistance and body fat measures in 221 middle-aged nondiabetic men. Bioavailable and free testosterone were calculated from the concentrations of total testosterone, SHBG, and albumin, and they were not significantly correlated with SHBG (r = 0.07-0.1). In contrast, total testosterone correlated significantly with SHBG (r = 0.63). We evaluated the relationship between these measures of circulating testosterone and markers for insulin resistance (i.e., fasting insulin, C-peptide, and homeostasis model assessment for insulin resistance [HOMA-IR]) as well as total body fat (assessed by dual-energy X-ray absorptiometry [DEXA]) and abdominal fat distribution (assessed by single-slice computed tomography [CT]). Bioavailable, free, and total testosterone and SHBG all correlated significantly with fasting insulin (age-adjusted r = -0.15 [P = 0.03], -0.14 [P = 0.03], -0.32 [P < 0.0001], and -0.38 [P < 0.0001], respectively), fasting C-peptide (r = -0.18 [P = 0.009] to -0.41 [P < 0.0001]), HOMA-IR (r = -0.15 [P = 0.03] to - 0.39 [P < 0.0001]), and body fat measures (r = -0.17 [P = 0.008] to -0.44 [P < 0.0001]). Only SHBG and total testosterone were significantly associated with fasting glucose (r = -0.20 [P = 0.003] to -0.21 [P = 0.002]). In multivariate analysis, bioavailable or free testosterone was significantly and inversely associated with insulin, C-peptide, and HOMA-IR, but this was not independent of total body or abdominal fat. SHBG was a significant determinant of insulin, C-peptide, and HOMA-IR, independent of body fat. The associations between total testosterone and insulin resistance were confounded by SHBG. The inverse association between testosterone and insulin resistance, independent of SHBG, was mediated through body fat.
Baerwald et al. (1) proposed a new model for ovarian follicular development in the human menstrual cycle. They showed additional waves of follicular development in the follicular and luteal phase of normal ovulatory cycles. Although no additional ovulation was observed, the authors speculated that the anovulatory follicles from the additional waves of follicular development may be able to ovulate in the presence of an additional LH surge.
Fertility AwarenessPregnancy Probability ModelsEffectiveness EstimationEfficacy Assessment
Intercourse results in a pregnancy essentially only if it occurs during the 6-day fertile interval ending on the day of ovulation. The strong association between timing of intercourse within this interval and the probability of conception typically is attributed to limited sperm and egg life times. A total of 782 women recruited from natural family planning centres in Europe contributed prospective data on 7288 menstrual cycles. Daily records of intercourse, basal body temperature and vaginal discharge of cervical mucus were collected. Probabilities of conception were estimated according to the timing of intercourse relative to ovulation and a 1-4 score of mucus quality. There was a strong increasing trend in the day-specific probabilities of pregnancy with increases in the mucus score. Adjusting for the mucus score, the day-specific probabilities had limited variability across the fertile interval. Changes in mucus quality across the fertile interval predict the observed pattern in the day-specific probabilities of conception. To maximize the likelihood of conception, intercourse should occur on days with optimal mucus quality, as observed in vaginal discharge, regardless of the exact timing relative to ovulation.
A surprising set of recent observations suggests a link between assisted reproductive technology (ART) and epigenetic errors--that is, errors involving information other than DNA sequence that is heritable during cell division. An apparent association with ART was found in registries of children with Beckwith-Wiedemann syndrome, Angelman syndrome, and retinoblastoma. Here, we review the epidemiology and molecular biology behind these studies and those of relevant model systems, and we highlight the need for investigation (1) large-scale case-control studies of ART outcomes, including long-term assessment of the incidence of birth defects and cancer, and (2) investigation of the relationship between epigenetic errors in both offspring and parents, the specific methods of ART used, and the underlying infertility diagnoses. In addition, the components of proprietary commercial media used in ART procedures must be fully and publicly disclosed, so that factors such as methionine content can be assessed, given the relationship in animal studies between methionine exposure and epigenetic changes.
This study was undertaken to determine proportions of very-low-birth-weight (VLBW) multiple birth infants receiving neonatal intensive care whose mothers received various types of infertility treatment and to evaluate infertility treatment-associated morbidity and mortality. Study infants were multiples with birth weight 401 to 1500 g cared for in Cincinnati neonatal intensive care units from January 1996 to December 2000. Data were obtained retrospectively from the National Institute for Child Health and Human Development Neonatal Research Network registry. Use of infertility treatment (in vitro fertilization, injection or oral ovulation, and intrauterine insemination) was determined by maternal interview or chart review. The generalized estimating equation approach to logistic regression was used. The study included 382 infants of 212 201=spontaneous conception (53%), 93=in vitro fertilization (24%), 55=injection (14%), 15=oral (4%), and 18=intrauterine insemination (5%). Neither gestational age nor birth weight differed between groups. More female (58%, P=.003) and white infants (95%, P<.001) resulted from infertility treatment-induced pregnancies than from spontaneous pregnancies. Advancing gestational age significantly decreased odds for all outcomes. Of VLBW multiples receiving neonatal intensive care, 47% are associated with infertility treatment. Infertility treatment does not influence outcomes in VLBW multiples.
Body LiteracyProfessional Training ProgramsHealthcare Provider EducationDistance Education
Nurses and other health care professionals often have little knowledge of methods of natural family planning (NFP) and do not readily prescribe natural methods for their patients. One reason for this is that little or no information on NFP is provided in nursing or medical schools. The holistic, informational, and integrative nature of NFP fits well with professional nursing practice. A university online distance education NFP teacher training program, which offers academic credit and includes theory, practice, and the latest developments in fertility monitoring, has been developed for health care professionals. Professional NFP services in the United States need to meet worldwide standards and include documenting and assessing pregnancy outcomes, tailoring NFP services to the client or couple, and simplifying them for ease of use in a standard health care practice.
Imprecise measures of ovulation obscure the relationship between women's sexuality and the menstrual cycle, as does studying women with different contraceptive goals in different social contexts. Here we present a novel noninvasive method to precisely pinpoint the preovulatory surge of Luteinizing Hormone (LH), demarcating hormonally distinct cycle phases with greater than 95% reliability. Women were more sexually active on days prior to and including the preovulatory (LH) surge. This pattern was evident only when women initiated sexual activity and not when their partners did, indicating an increase in women's sexual motivation rather than attractiveness. A second study replicated the 6-day increase in sexual activity beginning 3 days before the LH surge, accompanied by stronger sexual desire and more sexual fantasies. We propose the term 'sexual phase' of the cycle, since follicular phase is over inclusive and ovulatory phase is not sufficient. These findings are striking because the women were avoiding pregnancy and were kept blind to the hypotheses, preventing expectation bias. The sexual phase was more robust in women with regular sexual partners, although the increase in sexual desire was just as great in nonpartnered women, who also reported feeling less lonely at this time. We use these results to evaluate potential neuroendocrine mechanisms underlying women's sexual motivation and activity.
Experimental data suggest that placental growth factor (PlGF), a member of the vascular endothelial growth factor family, acts as a primary inflammatory instigator of atherosclerotic plaque instability and thus may be useful as a risk-predicting biomarker in patients with acute coronary syndromes (ACS). To determine whether blood levels of PlGF predict risk for death or nonfatal myocardial infarction in patients with acute chest pain. DESIGN, SETTING, Measurement of PlGF levels as well as levels of markers of myocardial necrosis (troponin T [TnT]), platelet activation (soluble CD40 ligand [sCD40L]), and inflammation (high-sensitivity C-reactive protein [hsCRP]) in an inception cohort of 547 patients with angiographically validated ACS participating in the CAPTURE (c7E3 Fab Anti-Platelet Therapy in Unstable Refractory Angina) trial and in a heterogeneous cohort of 626 patients presenting with acute chest pain to an emergency department in Germany between December 1996 and March 1999. Risk for death or nonfatal myocardial infarction after 30 days. In patients with ACS, elevated PlGF levels (>27.0 ng/L; 40.8% of patients) indicated a markedly increased risk of events at 30 days (14.8% vs 4.9%; unadjusted hazard ratio [HR], 3.34; 95% confidence interval [CI], 1.79-6.24; P<.001). In a multivariable model, elevated levels of TnT (HR, 1.83; 95% CI, 1.05-3.86; P =.03), sCD40L (HR, 2.65; 95% CI, 1.41-4.99; P =.002), and PlGF (HR, 3.03; 95% CI, 1.54-5.95; P<.001) were independent predictors, while elevated hsCRP level was not (HR, 0.98; 95% CI, 0.53-1.98; P =.94). In patients with acute chest pain, elevated levels of PlGF predicted risk (21.2% vs 5.3%) (unadjusted: HR, 4.80; 95% CI, 2.81-8.21; P<.001; HR, 3.00; 95% CI, 1.68-5.38; P<.001). Patients negative for all 3 markers (TnT, sCD40L, and PlGF) were at very low cardiac risk (7 no event; 30 2.1% event rate). Plasma PlGF levels may be an independent biomarker of adverse outcome in patients with suspected ACS. A single initial measurement of plasma PlGF appears to extend the predictive and prognostic information gained from traditional inflammatory markers.
The purpose of this study was to determine the incidence of neurologic morbidity in preterm monochorionic (MC) and dichorionic (DC) twins. We collected perinatal, neonatal, and infant follow-up data of 76 MC and 78 DC twins born between 24 and 34 weeks of gestation (295 infants). Risks of neuromorbidity in the surviving infants were evaluated in relation to chorionicity, discordant birth weight (>20%), twin-twin transfusion syndrome (TTTS), and cotwin death. The overall incidence of cerebral palsy and minor neurologic disabilities in surviving twins was 4% and 9%, respectively. MC infants had a higher incidence of cerebral palsy (8% vs 1%, P<.05) and neurologic morbidity (15% vs 3%, P<.05) than DC infants. The risk of impaired neurodevelopment was higher in MC infants with discordant birth weight (42%, P<.01), TTTS (37%, P<.01), and cotwin death (60%, P<.01) than those with concordant birth weight (8%). In MC pregnancies, the cerebral palsy risk was higher in infants with discordant birth weight than those with chronic TTTS (19% vs 4%, P<.05). Similarly, discordant DC infants had higher neuromorbidity than concordant group (5% vs 1%, P<.05). In both MC and DC discordant infants, neurologic morbidity was independent of growth restriction. Neurologic morbidity in the preterm MC infants was 7-fold higher than DC infants because of chronic TTTS, discordant birth weight, and cotwin death in utero.
General OB/GYNEpidemiology and PreventionSexually Transmitted InfectionsSTD Risk Factors
Sexually transmitted diseases (STDs) constitute a major health burden in the United States, causing pelvic inflammatory disease, ectopic pregnancy, infertility, chronic pelvic pain, genital lesions, genital neoplasms, adverse pregnancy outcomes, immune system dysfunction, liver disease, and even death. STDs disproportionately affect adolescents and young adults. Of the estimated 15 million STDs that occur annually each year in the United States, 4 million are among adolescents and 6 million among young adults. The current epidemic is complicated by the high asymptomatic carrier state associated with most STDs and the inadequate protection of condoms in preventing transmission. Sexually active individuals, particularly adolescents, must be educated on the ramifications of early onset of sexual activity and the health consequences of multiple sexual partners.
Fertility AwarenessClearplan Easy Fertility MonitorComparison with Hormonal MarkersElectronic Monitors vs Biomarkers
The purpose of this study was to compare the fertile phase of the menstrual cycle as determined by the Clearplan Easy Fertility Monitor (CPEFM) with self-monitoring of cervical mucus. One-hundred women (mean age = 29.4 years) observed their cervical mucus and monitored their urine for estrogen and luteinizing hormone metabolites with the CPEFM on a daily basis for 2-6 cycles and generated 378 cycles of data; of these, 347 (92%) had a CPEFM peak. The beginning of the fertile window was, on average, day 11.8 (SD = 3.4) by the monitor and day 9.9 (SD = 3.0) by cervical mucus (r = 0.43, p < 0.001). The average first day of peak fertility by the monitor was 16.5 (SD = 3.6) and by cervical mucus 16.3 (SD = 3.7) (r = 0.85, p < 0.001). The mean length of the fertile phase by the monitor was 7.7 days (SD = 3.1) and by cervical mucus 10.9 days (SD = 3.7) (t = 12.7, p < 0.001). The peak in fertility as determined by the monitor and by self-assessment of cervical mucus is similar but the monitor tends to underestimate and self-assessment of cervical mucus tends to overestimate the actual fertile phase.
PCOSRotterdam Consensus CriteriaHyperandrogenism and Insulin ResistanceCardiovascular and Metabolic
Since the 1990 National Institutes of Health-sponsored conference on polycystic ovary syndrome (PCOS), it has become appreciated that the syndrome encompasses a broader spectrum of signs and symptoms of ovarian dysfunction than those defined by the original diagnostic criteria. The 2003 Rotterdam consensus workshop concluded that PCOS is a syndrome of ovarian dysfunction along with the cardinal features hyperandrogenism and polycystic ovary (PCO) morphology. PCOS remains a syndrome, and as such no single diagnostic criterion (such as hyperandrogenism or PCO) is sufficient for clinical diagnosis. Its clinical manifestations may include menstrual irregularities, signs of androgen excess, and obesity. Insulin resistance and elevated serum LH levels are also common features in PCOS. PCOS is associated with an increased risk of type 2 diabetes and cardiovascular events.
PCOSMetforminPulsatility and PCOSInsulin Resistance in Nonobese Patients
To evaluate the effects of metformin administration on spontaneous LH episodic release in a group of nonobese polycystic ovary (PCOS) patients. Controlled clinical study. PCOS patients in a clinical research environment. PATIENT(S): Twenty nonobese PCOS patients were enrolled after informed consent. INTERVENTION(S): All patients underwent hormonal evaluations and a pulsatility study (sampling every 10 minutes for 4 hours) before and at the sixth month of therapy (metformin, 500 mg, p.o. b.i.d.). Ultrasound examinations and Ferriman-Gallwey scoring were also performed. MAIN OUTCOME MEASURE(S): Measurements of plasma LH, FSH, estradiol (E(2)), androstenedione (A), 17-hydroxy-progesterone (17-OHP), and testosterone (T), glucose, insulin, and C-peptide concentrations. RESULT(S): After 6 months of metformin administration, the plasma LH, 17-OHP, A, and T levels and LH/FSH ratio were significantly reduced. Insulin sensitivity, expressed as the glucose-to-insulin ratio, was significantly improved under glucose load after 6 months of treatment. Spontaneous LH episodic release showed a significant reduction in pulse amplitude with no changes in pulse frequency. Menstrual cyclicity was restored in all amenorrheic and oligomenorrheic women. The ovarian volume and Ferriman-Gallwey scores also were significantly reduced. CONCLUSION(S): Metformin administration improves reproductive axis functioning in hyperandrogenic nonobese PCOS patients. By acting on the ovary and restoring normal ovarian activity, metformin positively modulates the reproductive axis (namely GnRH-LH episodic release).
PregnancyExtreme Prematurity OutcomesNeurodevelopmental Follow-upSurvival and Long-term Prognosis
Long-term outcome, including school-age function, has been infrequently reported in infants born at ages as young as 23-26 weeks' gestation. The objective of this study is to report outcome on a large cohort of these infants to understand better the risks and factors that affect survival and long-term prognosis. Records from 1036 infants who were born between January 1, 1986, and December 31, 2000, were analyzed retrospectively by logistic regression to correlate multiple factors with both survival and long-term outcome. A total of 675 surviving infants were analyzed at a mean age of 47.5 months for developmental outcome. A subset of 147 surviving infants who were born before 1991 were followed through school-age years using the University of Vermont Achenbach Child Behavioral Checklist and Teachers Report Form. Longitudinal follow-up was performed comparing 1-year outcome with school-age performance. Gestational age and recent year of birth correlated highly with survival. Maternal nonwhite race, female sex, inborn status, surfactant therapy, single gestation, and secondary sepsis also correlated positively with survival. Normal cranial ultrasound results, absence of chronic lung disease, female sex, cesarean delivery, and increased birth weight correlated favorably with long-term outcome. Infants who were born at 23 weeks were more likely to have severe impairments compared with those who were born at 24-26 weeks. Early follow-up identified most subsequent physical impairments but correlated poorly with school-age function. Survival continues to improve for infants who are born at extremely early gestational ages, but long-term developmental concerns continue to be prevalent. Early outcomes do not reliably predict school-age performance. Strategies that reduce severe intraventricular hemorrhage and chronic lung disease will likely yield the best chances to improve long-term outlook.
Fertility AwarenessScientific FoundationsBiophysical Properties and Mucus TypingHormonal and Ultrasound Correlation
Hilgers TW, 2004·The Medical and Surgical Practice of NaProTECHNOLOGY
The CREIGHTON MODEL FertilityCare System (CrMS) rests on a decades-long body of research demonstrating that cervical mucus functions as a physiologically regulated biological valve, opening predictably at the periovulatory estrogen rise and closing in the post-Peak phase. Chapter 15 of Hilgers (2004) synthesizes hormonal, ultrasound, cytologic, and biophysical evidence to establish that a woman's external observation of her Peak Day reliably identifies the fertile window, and documents the system's effectiveness data for both achieving and avoiding pregnancy across a five-study meta-analysis of nearly 1,900 couples.