Diaphragmatic endometriosis: diagnosis, surgical management, and long-term results of treatment

Abstract:
OBJECTIVE: To describe symptoms, surgical diagnosis and treatment, and long-term outcome of patients with symptomatic diaphragmatic endometriosis.

DESIGN: Observational follow-up study.

SETTING: American tertiary referral center for the surgical treatment of endometriosis.

PATIENT(S): Eight patients with diaphragmatic endometriosis causing severe or disabling symptoms.

INTERVENTION(S): Laparoscopic diagnosis of diaphragmatic endometriosis followed by upper abdominal laparotomy for full-thickness resection of the diaphragm.

MAIN OUTCOME MEASURE(S): Reduction of several symptoms as measured on a 5-point ranked ordinal scale administered by a phone survey up to 7 years after surgery.

RESULT(S): Laparoscopy from an umbilical port may identify small "sentinel lesions" of endometriosis on the anterior or mid diaphragm. Eight symptomatic patients all had significant invasive disease with dimensions up to 5 cm across of the posterior right diaphragm, which could not always be seen from the umbilical port site. All such lesions can be seen by a laparoscope placed beneath the right costal margin. Laparoscopic treatment of symptomatic disease is not rational given the posterior placement of the disease out of sight behind the liver and the full-thickness nature of the disease in all eight patients. Laparotomy with full thickness resection of the diaphragm resulted in complete eradication of symptoms in seven of eight patients, and good symptomatic reduction in one.

CONCLUSION(S): Treatment of diaphragmatic endometriosis by laparotomy results in a high rate of symptom relief. Laparoscopic treatment of diaphragmatic endometriosis will result in a high rate of incomplete diagnosis and incomplete treatment with a high rate of continuing symptoms.


Acute respiratory failure and short-term outcome after premature rupture of the membranes and oligohydramnios before 20 weeks of gestation

Abstract:
OBJECTIVES: To study the effect of premature rupture of membranes and oligohydramnios before 20 weeks of gestation (PROM20) on acute respiratory morbidity and on short-term outcome in infants with a gestational age >or=24 weeks.

STUDY DESIGN: A historic cohort study was performed of all infants born after PROM20 with a gestational age greater-than-or-equal24 weeks between 1990 and 1999. Control infants were matched for year of birth, gestational age, and birth weight.

RESULTS: PROM20 infants had an increased acute respiratory morbidity (higher ventilator settings and increased incidence of hypoxemia, hypercapnia, and pulmonary hypertension) and a trend to more air leaks. Although not statistically different, PROM20 infants had more complications (neonatal survival, 68% vs 95%; severe intracranial hemorrhage, 31% vs 6%; chronic lung disease in surviving infants, 46% vs 17%). The relative risk for combined morbidity (death, intracranial hemorrhage, chronic lung disease) was increased (3.0, P =.019) when compared with matched control infants. However, 31% of the surviving PROM20 infants were discharged without apparent morbidity.

CONCLUSIONS: Expectant treatment in women with PROM20 and present neonatal intensive care has improved the survival of PROM20 infants despite severe initial respiratory failure. However, chronic morbidity still occurred.


Obstetric, somatic, and demographic risk factors for postpartum depressive symptoms

Abstract:
OBJECTIVE: To identify and test the predictive power of potential independent risk factors of postpartum depressive symptoms during pregnancy and the perinatal period.

METHODS: We conducted a case-control study where 132 women with postpartum depressive symptoms were selected as an index group and 264 women without depressive symptoms as a control group. Data related to sociodemographic status, medical, gynecologic, and obstetric history, pregnancy, and perinatal events were collected from standardized medical records.

RESULTS: The strongest risk factors for postpartum depressive symptoms were sick leave during pregnancy and a high number of visits to the antenatal care clinic. Complications during pregnancy, such as hyperemesis, premature contractions, and psychiatric disorder were more common in the postpartum depressed group of women. No association was found between parity, sociodemographic data, or mode of delivery and postpartum depressive symptoms.

CONCLUSION: Women at risk for postpartum depression can be identified during pregnancy. The strongest risk factors, sick leave during pregnancy and many visits to the antenatal care clinic, are not etiologic and might be of either behavioral or biologic origin. The possibilities of genetic vulnerability and hormonal changes warrant further investigation to reach a more thorough understanding.


Implantation and the survival of early pregnancy

Abstract: The implantation of fertilized ova and the formation of the placenta are crucial steps in reproduction. This review summarizes current information about these steps, including some of the molecular mechanisms that mediate them and how they may go awry, with consequent loss of the pregnancy.


Factors influencing women's satisfaction with birth control methods

B J Oddens

International Health Foundation, Geneva, Switzerland. info@ihf.nl

D den Tonkelaar

Abstract:
Objectives: To study the extent to which variation in satisfaction with a birth control method is explained by variation in perceived physical and psychological effects.

Methods: A population survey among 1466 German women was carried out. Within the overall sample, 1303 women had ever used oral contraceptives, 996 had relied on condoms, 342 had ever used intrauterine devices (IUD), 428 had used natural family planning and 139 women were sterilized. For each method a woman had ever used, she answered questions about satisfaction with the method, concerns about getting pregnant or suffering health risks during use, ease of use, changes in sexual relationship, relationship with the partner and mood. Past and current users of oral contraceptives and IUDs and sterilized women additionally reported changes in menstrual bleeding.

Results: Variation in satisfaction was, for a large part, explained by variation in health concerns among oral contraceptive users, by variation in perceived changes in the quality of the sexual relationship among condom users, by perceived ease of use among IUD users and sterilized women, and by variation in pregnancy concern among natural family planning users.

Conclusion: Counselling about these perceived experiences is most likely to result in greater satisfaction and therefore improved compliance.

The European Journal of Contraception & Reproductive Health Care : the Official  Journal of the European Society of Contraception


Amniotic fluid infection, cytokines, and adverse outcome among infants at 34 weeks' gestation or less

Abstract:
OBJECTIVE: We examined the hypothesis that amniotic fluid (AF) infection and elevated cytokine concentrations may cause neonatal injury beyond that expected solely from prematurity.

METHODS: The effects of exposure to AF infection and elevated cytokine concentrations were measured in 151 infants born to afebrile women in preterm labor with intact membranes at less than or equal to 34 weeks' gestation. Amniotic fluid was collected by amniocentesis for culture and determination of tumor necrosis factor-alpha and interleukin-6. Cytokine concentrations, stratified by AF infection, were compared for three gestational age groups. We then examined the associations between a positive AF culture or elevated AF tumor necrosis factor-alpha concentration and adverse neonatal outcomes, adjusted for birth weight.

RESULTS: Amniotic fluid from 45 (30%) of 151 pregnancies had microorganisms, an elevated tumor necrosis factor-alpha concentration, or both. Amniotic fluid cytokine concentrations were significantly higher among women in preterm labor at less than or equal to 30 weeks, compared with 31-34 weeks. Nine of 11 infants who died at less than or equal to 24 hours of age had AF infection or elevated AF tumor necrosis factor-alpha. For the 140 surviving infants, AF infection and/or an elevated AF tumor necrosis factor-alpha was associated with respiratory distress syndrome (adjusted odds ratio [OR] 1.7), grade 3-4 intraventricular hemorrhage (adjusted OR 2.2), necrotizing enterocolitis (adjusted OR 1.8), and multiple organ dysfunction (adjusted OR 3.0).

CONCLUSION: Among infants born at less than or equal to 34 weeks to women who have intact membranes and are initially afebrile, those exposed to AF bacteria or cytokines have more adverse neonatal outcomes than unexposed infants of similar birth weight.


The Creighton Model FertilityCare™ System, An Introductory Booklet for New Users

Thomas W Hilgers

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


Physicians' Desk Reference (PDR), 57th Edition


The Creighton Model FertilityCare™ System: A Standardized Case Management Approach to Teaching. Book I — Basic Teaching Skills, 2nd Edition


The ageing female reproductive axis II: ovulatory changes with perimenopause

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: Perimenopause, a complex physiological transition for midlife women, begins with changes in experiences many years before cycles become irregular, oestradiol levels decrease or follicle-stimulating hormone levels increase. Erratic and average higher oestradiol levels as well as shorter luteal phase lengths and lower progesterone levels occur during perimenopause. These ovarian changes may be causally related to lower inhibin production but the dynamic prospective inter-relationships within women are not well documented. This review will first define perimenopause and then explore the limited published data on ovulatory characteristics in perimenopause. In addition, it will report preliminary prospective observational data on menstrual cycles and ovulation in initially ovulatory women followed through the perimenopause. Prospective data suggest that ovulation disturbances begin early in perimenopause and increase with irregular cycles. Combined with higher oestradiol levels they may cause menorrhagia. It is not yet known whether disturbances of ovulation relate to bone loss in perimenopausal, as in premenopausal, women. It is also not known whether progesterone therapy can effectively counteract the end organ (breast, endometrial, brain) effects of higher/erratic oestradiol levels and effectively treat perimenopausal vasomotor and other symptoms.


A new monophasic oral contraceptive containing drospirenone. Effect on premenstrual symptoms

Abstract:
Objective: To determine whether a new monophasic oral contraceptive containing drospirenone/ethinyl estradiol reduces premenstrual symptoms.

Study Design: In an open-label study measuring intrasubject changes in premenstrual symptoms and comparing effects between women who were new users of oral contraceptives and those who switched from previous contraceptives, ethinyl estradiol (30 micrograms) and drospirenone (3 mg) were administered for 13 menstrual cycles to 326 healthy women aged 18-35 years. Subjects completed the 23-item Women's Health Assessment Questionnaire at baseline and at the end of the sixth cycle.

Results: At the end of cycle 6, premenstrual and menstrual symptom scores on the negative affect and water retention scales were reduced significantly relative to baseline, as was increased appetite during the premenstrual and menstrual phases. Similar improvements were seen among new users of hormonal contraceptives and those who switched from previous contraceptives. Impaired concentration scale scores were not significantly reduced from baseline, and assessments of undesired hair changes and feelings of well-being did not change appreciably.

Conclusion: An oral contraceptive containing drospirenone/ethinyl estradiol may reduce the premenstrual symptoms of negative affect, water retention and increased appetite.


Surgical Techniques of Open Myomectomy

Surgical Techniques of Open Myomectomy

Operative Techniques in Gynecologic Surgery


DIR Jahrbuch 2001 (Deutsches IVF-Register Annual Report 2001)

Abstract: Annual report (Jahrbuch) of the Deutsches IVF-Register (DIR) for treatment year 2001. 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).


The epidemiology of endometriosis

The epidemiology of endometriosis

Annals of the New York Academy of Sciences


Screening Tests To Detect Chlamydia trachomatis and Neisseria gonorrhoeae Infections--2002

Centers for Disease Control and Prevention

Abstract: Since publication of CDC's 1993 guidelines (CDC, Recommendations for the prevention and management of Chlamydia trachomatis infections, 1993. MMWR 1993;42[No. RR-12]:1-39), nucleic acid amplification tests (NAATs) have been introduced as critical new tools to diagnose and treat C. trachomatis and Neisseria gonorrhoeae infections. NAATs for C. trachomatis are substantially more sensitive than previous tests. When using a NAAT, any sacrifice in performance when urine is substituted for a traditional swab specimen is limited, thus reducing dependence on invasive procedures and expanding the venues where specimens can be obtained. NAATs can also detect both C. trachomatis and N. gonorrhoeae organisms in the same specimen. However, NAATs are usually more expensive than previous tests, making test performance from an economic perspective a key consideration. This report updates the 1993 guidelines for selecting laboratory tests for C. trachomatis with an emphasis on screening men and women in the United States. (In this report, screening refers to testing persons in the absence of symptoms or signs indicating C. trachomatis or N. gonorrhoeae infection.) In addition, these guidelines consider tests from an economic perspective and expand the previous guidelines to address detection of N. gonorrhoeae as well as C. trachomatis infections. Because of the increased cost of NAATs, certain laboratories are modifying manufacturers' procedures to improve test sensitivity without incurring the full cost associated with screening with a NAAT. Such approaches addressed in these guidelines are pooling of specimens before testing with a NAAT and additional testing of specimens whose non-NAAT test result is within a gray zone. This report also addresses the need for additional testing after a positive screening test to improve the specificity of a final diagnosis. To prepare these guidelines, CDC staff identified pertinent concerns, compiled the related literature published during 1990 or later, prepared tables of evidence, and drafted recommendations. Consultants, selected for their expertise or disciplinary and organizational affiliations, reviewed the draft recommendations. These final guidelines are the recommendations of CDC staff who considered contributions from scientific consultants. These guidelines are intended for laboratorians, clinicians, and managers who must choose among the multiple available tests, establish standard operating procedures for collecting and processing specimens, interpret test results for laboratory reporting, and counsel and treat patients.


Was Sampson wrong?

Was Sampson wrong?


Reproductive Anatomy and Physiology: A Primer for FertilityCare Professionals


Combination OCs and Prescribed Antibiotics


The Creighton Model FertilityCare™ System: A Standarized, Case Management Approach to Teaching


The Boston IVF Handbook of Infertility

The Boston IVF Handbook of Infertility


Impact of progestins on estrogen-induced neuroprotection: synergy by progesterone and 19-norprogesterone and antagonism by medroxyprogesterone acetate

Abstract: Estrogen replacement therapy is associated with improvement of cognitive deficits and reduced incidence of Alzheimer's disease. To compare the impact of therapeutically relevant progestins on estrogen-induced neuroprotection, we treated primary hippocampal neuron cultures with 17beta-E2 and progestin, alone and in combination, 48 h before glutamate insult. Estrogen, progesterone, and 19-norprogesterone, alone or in combination, protected against glutamate toxicity. In contrast, medroxyprogesterone acetate (MPA) failed to protect against glutamate toxicity. Not only was MPA an ineffective neuroprotectant but it attenuated the estrogen- induced neuroprotection when coadministered. We addressed the role of MAPK activation in neuroprotection by ovarian steroids. Estrogen and all three progestins tested, alone or in combination, activated MAPK, indicating another mechanism of protection. Bcl-2 expression has been shown to prevent cell death and is up-regulated by 17beta-E2. Progesterone and 19-norprogesterone, alone or in combination with estrogen, increased Bcl-2 expression. In contrast, MPA blocked estrogen-induced Bcl-2 expression when coadministered. These results may have important implications for the effective use of hormone replacement therapy in the maintenance of neuronal function during menopause and aging and for protection against neurodegenerative diseases such as Alzheimer's disease.


Periodic abstinence and calendar method use in Hungary, Peru, the Philippines,  and Sri Lanka

Research Group on Methods for the Natural Regulation of Fertility**e1

Catherine d'Arcangues

Special Programme of Research, Development, and Research Training in Human Reproduction, Geneva, Switzerland. darcanguesc@who.ch

Abstract: Focus group research was conducted in four countries to understand how couples who use calendar methods determine when they are at risk of pregnancy, what behavior they adopt during the fertile phase, and whether or not they are satisfied with their method. Calendar and periodic abstinence method users do not all know how to make correct calendar calculations of the fertile period, report being sexually active during the fertile period, and desire a more comprehensive approach to sexual behavior during the fertile period. Men's roles in the methods should be enhanced, and credible resources in the community should be enlisted to improve education, information, and communication.


Premenstrual dysphoric disorder and risk for major depressive disorder: a preliminary study

Abstract: Investigators examined whether premenstrual dysphoric disorder (PMDD) poses a risk for major depressive disorder (MDD). In an initial study, women rated premenstrual symptoms and functional impairment daily for two menstrual cycles. A semistructured diagnostic interview was given to obtain psychiatric histories and differentiate PMDD from premenstrual exacerbations of other disorders. Participants in this pilot study were eight women with PMDD and a random subgroup without PMDD (n = 9) initially. Another semistructured interview was given to diagnose psychiatric disorders occurring during a two-year follow-up interval. In all, seven of the eight women with PMDD developed MDD within two years, including all those who had never had MDD before. The odds that a woman with PMDD developed MDD were 14 times the odds that a woman without PMDD developed MDD ( p <.05). Premenstrual dysphoric disorder may be a prodrome of or causal risk factor for MDD. Preliminary evidence for the diagnostic validity of PMDD is provided.


Luteal function as the main determinant of pregnancy outcome: successful prevention of spontaneous abortion, prematurity and IUGR


Postnatal increase of procalcitonin in premature newborns is enhanced by chorioamnionitis and neonatal sepsis

Abstract:
BACKGROUND: To determine the influence of chorioamnionitis and neonatal sepsis on procalcitonin (PCT) levels in very-low-birth-weight (VLBW) infants within the first week of life.

DESIGN: PCT serum levels were measured in cord blood 1 h after delivery and on day 3 and day 7 of life. Chorioamnionitis and neonatal sepsis within the first week were monitored.

RESULTS: Chorioamnionitis was present in eight of 37 patients (21.6%). PCT on day 3 was increased in both the "No chorioamnionitis" (2.54 ng mL(-1), SEM 0.51) and "Chorioamnionitis" (6.96 ng mL(-1), SEM 2.93) groups of VLBW infants compared with the 1st hour values (0.45 and 0.58 ng mL(-1) SEM 0.07 and 0.11, respectively, P < 0.001) of the same patients. The postnatal gain was higher in the "Chorioamnionitis" group (P < 0.01). Neonatal sepsis was diagnosed (after exclusion) in 12 of 32 patients (37.5%). Mean values of maximum PCT in patients with and without sepsis were 8.41 ng mL(-1) (SEM 1.87) and 3.02 ng mL(-1) (SEM 1.38), respectively (P < 0.05). Sensitivity to sepsis of PCT, ratio of immature to total neutrophils (I : T), and C-reactive protein (CRP) were 75%, 50% and 25%, respectively.

CONCLUSIONS: In the group of VLBW infants the PCT level within 72 h of delivery was markedly increased in patients with chorioamnionitis. Compared with I : T and CRP, PCT appears to be a more sensitive marker of neonatal sepsis.

European Journal of Clinical Investigation


A randomized study comparing Crinone 8% and intramuscular progesterone supplementation in in vitro fertilization-embryo transfer cycles

Abstract:
OBJECTIVE: To compare the efficacy of Crinone 8% intravaginal progesterone gel vs. IM progesterone for luteal phase and early pregnancy support after IVF-ET.

DESIGN: Randomized, open-label study.

SETTING: Academic medical center.

PATIENT(S): Two hundred and one women undergoing IVF-ET.

INTERVENTION(S): Women were randomized to supplementation with Crinone 8% (90 mg once daily) or IM progesterone (50 mg once daily) beginning the day after oocyte retrieval.

MAIN OUTCOME MEASURE(S): Pregnancy, embryo implantation, and live birth rates.

RESULT(S): The women randomized to luteal phase supplementation with IM progesterone had significantly higher clinical pregnancy (48.5% vs. 30.4%; odds ratio [OR], 2.16; 95% confidence interval [CI], 1.21, 3.87), embryo implantation (24.1% vs. 17.5%; OR, 1.89; 95% CI, 1.08, 3.30), and live birth rates (39.4% vs. 24.5%; OR, 2.00; 95% CI, 1.10, 3.70) than women randomized to Crinone 8%.

CONCLUSION(S): In women undergoing IVF-ET, once-a-day progesterone supplementation with Crinone 8%, beginning the day after oocyte retrieval, resulted in significantly lower embryo implantation, clinical pregnancy, and live birth rates compared with women supplemented with IM progesterone.


Angiogenesis in the human corpus luteum: simulated early pregnancy by HCG treatment is associated with both angiogenesis and vessel stabilization

W Colin Duncan

From Tommy’s National Centre for Miscarriage Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham (A.C., A.J.D., V.C., H.H., L.J.M., I.D.G., H.W., A.K.E., T.R., C....

Abstract:
BACKGROUND: This study examined changes in the luteal vasculature throughout the menstrual cycle and during simulated pregnancy with human chorionic gonadotrophin (HCG) in the human.

METHODS: Endothelial cell and pericyte area were assessed by quantitative immunocytochemistry for CD34 and alpha-smooth muscle actin respectively, taking into consideration the dynamics of lutein cell hypertrophy and atrophy throughout the cycle and after HCG treatment. Endothelial cell proliferation was detected by Ki-67/CD34 dual staining and a proliferation index was obtained. The molecular regulation of angiogenesis was studied by examining changes in vascular endothelial growth factor (VEGF) immunostaining.

RESULTS: The early luteal phase is associated with intense angiogenesis, as indicated by high endothelial cell proliferation, and by the mid-luteal phase a mature vasculature was apparent, as shown by maximal endothelial cell and pericyte areas. During the late luteal phase, decreased endothelial proliferation, endothelial cell and pericyte area indicated vascular regression. HCG treatment induced a second burst of total and endothelial cell proliferation and a concomitant increase in endothelial cell and pericyte areas. VEGF protein was expressed throughout the luteal phase and a significant increase was found after HCG treatment.

CONCLUSION: Luteal rescue with HCG is associated with a second wave of angiogenesis and vascular stabilization.


Luteal estrogen supplementation in pregnancies associated with low serum estradiol concentrations

Abstract: The role of luteal phase estrogen in pregnancy outcome has been a matter of considerable debate. In order to evaluate the effectiveness of estrogen supplementation in gonadotropin releasing hormone agonist (GnRHa)/human menopausal gonadotropin (hMG)-stimulated cycles associated with low luteal estrogen concentration, a study was performed comparing the ongoing pregnancy rates in cycles with serum concentrations of estradiol (E2) <100 pg/ml 11 days post embryo transfer (p-ET), treated with luteal phase progesterone (P4) vs. E2 and P4 supplementation. Among 1106 serum samples studied, 951 were from women receiving GnRHa and follicle stimulating hormone (FSH) prior to oocyte retrieval and P4 (50 mg-100 mg IM daily) as luteal phase supplementation beginning day 11 after retrieval. The remaining 155 were from women receiving both E2 (2 mg-6 mg estrace orally each day) and P4 during the luteal phase. Significantly greater frequencies of preclinical losses were observed among women with human chorionic gonadotropin (hCG) concentrations>5 mIU/ml and concurrent E2 concentrations <100 pg/ml compared with E2 >100 pg/ml (p<0.00001). Among the 128 women who had hCG concentrations >5 mIU/ml and E2 concentrations <100 pg/ml, 102 received P4 only during the luteal phase and 26 were treated with estrace 2 mg-6 mg daily, as well as P4 during the luteal phase. The frequency of preclinical pregnancy losses among the 102 women with hCG >5 mIU/ml and E2 <100 pg/ml who did not receive luteal E2 supplementation was 72%, compared with 50% who received luteal E2 supplementation (p=0.04) The increase in preclinical pregnancy loss rates among women not receiving luteal E2 resulted in a decrease in ongoing pregnancy rate (8%), compared to those receiving luteal E2 supplementation (31%) (p=0.002). Our results indicated that a subset of women losing pregnancies preclinically after GnRHa and FSH stimulation due to low luteal phase serum E2 level may benefit from luteal estrogen supplementation. More sensitive and specific markers are needed to identify prospectively women in this risk group.


Lepidium meyenii (Maca) improved semen parameters in adult men

Abstract:
AIM: The present study was designed to determine the effect of a 4-month oral treatment with tablets of Lepidium meyenii (Maca) on seminal analysis in nine adult normal men aged 24-44 years old.

METHODS: Nine men received tablets of Maca (1500 or 3000 mg/day) for 4 months. Seminal analysis was performed according to guidelines of the World Health Organization (WHO). Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), testosterone (T) and estradiol (E2) were measured before and after treatment.

RESULTS: Treatment with Maca resulted in increased seminal volume, sperm count per ejaculum, motile sperm count, and sperm motility. Serum hormone levels were not modified with Maca treatment. Increase of sperm count was not related to dose of Maca.

CONCLUSION: Maca improved sperm production and sperm motility by mechanisms not related to LH, FSH, PRL, T and E2.


Perimenopausal bone loss: more than estrogen depletion

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Christine L Hitchcock

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

Abstract: To the Editor: In their recent article, "Characterization of Perimenopausal Bone Loss," Recker and colleagues present unique longitudinal bone mineral density (BMD) and hormonal data.1 We acknowledge the work involved in recruiting, motivating, and continuing to follow 75 women each for an average of 8 years. The data from this study are an important contribution to our knowledge of bone changes through the natural perimenopausal transition. Unfortunately, these authors have chosen to reduce the complex endocrinological and physiological changes of perimenopause2 to one idea—"estrogen deprivation." Our first concern is that "estrogen deprivation" or "depletion" is not an adequate concept with which to explain the rapid bone loss during perimenopause. The author's own data show that 50% of spinal BMD loss has occurred by 6 months before the final menstrual period at which time estradiol levels are not lower than in the so called "estrogen replete" group. In this study, perimenopausal bone loss appears to begin approximately 3 years before the final menstrual flow, which is about the time when menstrual cycles become irregular.3 Several other studies also show accelerated rates of perimenopausal bone loss.2, 4, 5 During these later phases of perimenopause, estradiol levels can be very high and certainly are not consistently low.2, 6, 7 If estradiol levels are not low in perimenopause, how can we explain the rapid bone loss? First, estradiol levels vary widely.2 Perhaps, acute drops in estradiol levels (often from abnormally high values) cause increased bone resorption much like that which has been shown to occur within seven days of premenopausal ovariectomy.8 A second possibility is that perimenopause causes psychosocial stress.9 Social stress coupled with high estradiol levels in men have been experimentally shown to cause increased cortisol levels10 that are known to be negative for bone. Finally, ovulatory changes that increase as women progress through perimenopause,11 are associated with accelerated cancellous bone loss, despite normal estradiol levels and regular cycles in premenopausal women.12 Replacement of luteal phases with cyclic progestin in a double-blind randomized study in premenopausal women with abnormal cycles caused an important positive change in spinal BMD.13 As a mechanism to allow use of all of their data, the authors labeled "estrogen replete" those women who continued to menstruate as well as those who started hormone therapy before menopause. It seems odd to us to combine data from three women who have undergone ovariectomy and seven women on exogenous hormone therapy with 10 preor perimenopausal women. The estrogen deprivation hypothesis has led the authors to overlook important physiological differences within this group. We request that the data for the 10 untreated preor perimenopausal women be provided and that we be told whether or not they continued to menstruate regularly. In women's life cycle, low levels of estrogen are as natural for menopausal women as for toddlers. To label menopause as a hormone deficiency condition is to ignore the normal hormonal pattern of women's lives. Recker and colleagues suggest that "hormone replacement therapy" should "begin as early as 2 years before the last menstrual period." Although we acknowledge that vasomotor symptoms commonly begin in perimenopause and have a very negative impact on quality of life, we suggest that progesterone would be a more appropriate therapy. Progesterone is truly low at this phase of perimenopause11 and is effective for night sweats/hot flushes. We fear that prescription of estrogen to women in late perimenopause may have negative consequences in both the short and the long-term. In the short term, it may exacerbate symptoms such as breast tenderness, headaches, and fluid retention. In the long term, having experienced side effects from estrogen treatment these women may refuse it when they are menopausal, a time when it has the potential to be valuable therapy. In summary, this important study is flawed because it relies on a clearly inadequate "estrogen deprivation" concept as the sole explanation for differences found in the prospective data from midlife women.

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research


Review of validation studies of the Edinburgh Postnatal Depression Scale

M Eberhard-Gran

Section of Epidemiology, National Institute of Public Health, Post Box 4404, Nydalen, N-0403 Oslo, Norway.

Abstract:
OBJECTIVE: To review validation studies of the Edinburgh Postnatal Depression Scale (EPDS).

METHOD: A systematic search was performed in Medline and the Science Citation Index Expanded (ISI) from the period 1987-2000. For sensitivity and specificity of the EPDS presented in each study, 95% confidence intervals were estimated. Positive and negative predictive values were estimated assuming prevalences of postpartum depression ranging from 5% to 20%.

RESULTS: Eighteen validation studies were identified. The study design varied between studies. The sensitivity and specificity estimates also varied: 65-100% and 49-100%, respectively. The confidence intervals were estimated to be wide. Our estimates suggest a lower positive predictive value in a normal population than in the validation study samples.

CONCLUSION: Most studies show a high sensitivity of the EPDS. Because of the differences in study design and large confidence intervals, uncertainty remains regarding the comparability between the sensitivity and specificity estimates of the different EPDS versions.


Estradiol/progesterone substitution in the luteal phase improves pregnancy rates in stimulated cycles--but only in younger women

Abstract: Innumerable studies have attempted to demonstrate that hormonal support of the luteal phase during ovulation induction cycles improves pregnancy rates. None has, however, so far been able to confirm the validity of such treatment conclusively, possibly because most studies only utilized progesterone substitution. Since luteal phase endometrium also requires estradiol support, this study attempted to investigate whether hormone substitution with progesterone and estradiol would be more successful in improving pregnancy rates. Amongst approximately 7500 consecutive ovulation induction cycles were identified prospectively which were characterized by a precipitous drop of luteal phase serum estradiol levels by more than 50% over a 48 hour period within 10 days from hCG administration. Those cycles were prospectively randomized to oral micronized estradiol substitution (Group I) or not (Group II), while both groups received routine progesterone substitution of the luteal phase. Cycles were then evaluated in regards to the occurrence of chemical, ectopic and clinical pregnancies. One hundred sixty-three Group I cycles resulted in 34 pregnancies (20.9%), which compared favorably to 21 pregnancies in 167 Group II patients (12.6%) (x2[1] = 4.06; p < 0.04). The advantage for Group I cycles (29/95 pregnancies, 31%) vs. Group II cycles (16/105, 15%) became even more pronounced when only women up to age 35 years were evaluated. Estradiol substitution maintained a significant advantage until age 38 (x2 [1] = 6.87; p < 0.009). While gravidity did not affect pregnancy success, estradiol substitution in Group I benefited nulliparous (23% pregnancy rate) over multiparous women (12% pregnancy rate) (x2 [2] = 6.86; p< 0.03). This association was, however, age-dependent. A combined estradiol and progesterone substitution of the luteal phase of ovulation induction cycles increases the overall pregnancy rate. Since estradiol substitution was initiated in this study only once a precipitous drop in serum estradiol levels had already taken place, an even larger improvement in pregnancy rates could conceivably be possible if earlier estradiol substitution of the luteal phase is initiated. A further expansion of investigations of similar protocols for routine ovulation induction and in vitro fertilization (IVF) cycles may be indicated, especially in women below age 38 years and in nulliparous females.


Improvement in insulin sensitivity followed by ovulation and pregnancy in a woman with polycystic ovary syndrome who was treated with rosiglitazone

Abstract:
OBJECTIVE: To determine the metabolic and reproductive effectiveness of rosiglitazone in polycystic ovary syndrome (PCOS).

DESIGN: Case report.

SETTING: Academic clinical practice and General Clinical Research Center.

PATIENT(S): A 25-year-old woman with PCOS.

INTERVENTION(S): Rosiglitazone maleate, 4 mg daily for 5 months until conception.

MAIN OUTCOME MEASURE(S): Insulin sensitivity by steady-state plasma glucose technique; serum androgens, progesterone, and hCG; and pelvic ultrasound images.

RESULT(S): Rosiglitazone treatment for 5 months improved insulin sensitivity, lowered serum free testosterone, and resulted in spontaneous ovulation and conception.

CONCLUSION(S): Rosiglitazone is a promising insulin sensitizer for treatment of PCOS. Clinical trials are warranted.


In vitro maturation and fertilization of oocytes from unstimulated normal ovaries, polycystic ovaries, and women with polycystic ovary syndrome

Abstract:
OBJECTIVE: To investigate differences in immature oocyte maturation, fertilization, and pregnancy rates among women with unstimulated normal ovaries, polycystic ovaries (PCOs), or PCOS.

DESIGN: Prospective observational study.

SETTING: University fertility clinic.

PATIENT(S): One hundred forty-four women undergoing 180 in vitro oocyte maturation treatment cycles.

INTERVENTION(S): Transvaginal immature oocyte recovery from unstimulated ovaries 36 hours after hCG priming. In vitro oocyte maturation and fertilization. Fresh embryo transfer.

MAIN OUTCOME MEASURE(S): Immature oocytes collected, metaphase II oocytes, and embryos produced. Implantation and pregnancy rates.

RESULT(S): The overall oocyte maturation and fertilization rates attained were 80.3% (1,222 of 1,522) and 76.5% (935 of 1,222), respectively. Significantly fewer immature oocytes were retrieved from normal ovaries (5.1 +/- 3.7) compared with the PCO (10.0 +/- 5.1) or PCOS (11.3 +/- 9.0) groups. Fertilization and cleavage rates were comparable among the three groups. The implantation, pregnancy, and live birth rates per transfer for normal ovaries were 1.5%, 4.0%, and 2.0%, respectively; for PCOs 8.9%, 23.1%, 17.3%, respectively; and for women with PCOS 9.6%, 29.9%, and 14.9%, respectively.

CONCLUSION(S): Immature oocytes retrieved from normal ovaries, PCOs, or women with PCOS, when using hCG priming before oocyte retrieval, have a similarly high maturation, fertilization, and cleavage potential. In vitro maturation is a useful treatment option, particularly for women with PCOs.


Executive summary: Stages of Reproductive Aging Workshop (STRAW)

Robert W. Rebar

American Society for Reproductive Medicine


Validation study of nonsurgical diagnosis of endometriosis

Paolo Vercellini

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

D L Olive

University of Arkansas for Medical Sciences

Abstract:
OBJECTIVE: To determine whether the surgical diagnosis of endometriosis can be predicted using symptoms, signs, and ultrasound findings.

DESIGN: Prospective study (study sample); retrospective record review (test sample).

SETTING: Hospital of Desio (study sample) and Mangiagalli Hospital (test sample), Italy.

PATIENT(S): Ninety women scheduled to undergo laparoscopy or laparotomy (study sample); 120 women who underwent laparoscopy (test sample).

INTERVENTION: The study sample group was interviewed before surgery about infertility and dysmenorrhea, dyspareunia, and noncyclic pelvic pain and each member had a pelvic examination and a transvaginal ultrasound. At surgery, endometriosis was noted. For the test sample, the same information was abstracted from medical records after laparoscopy.

MAIN OUTCOME MEASURE(S): The ability of symptoms, signs, and ultrasound to predict endometriosis at surgery. A classification tree was developed with the study sample and evaluated with the test sample.

RESULT(S): Ovarian endometriosis, but not nonovarian endometriosis, could be reliably predicted with noninvasive tools. Ultrasound and examination best predicted ovarian endometriosis, correctly classifying 100% of cases with no false positive diagnoses in the study sample. Similar results were found in the test sample.

CONCLUSION(S): Noninvasive tools may be used to identify women with ovarian, but not nonovarian endometriosis, with excellent agreement with surgical diagnosis.


Effect of metformin on mouse embryo development

Abstract:
Polycystic ovary syndrome (PCOS) is a common disorder affecting women of reproductive age. Its cardinal features are hyperandrogenism, chronic anovulation, and infertility. Some of the most important pathogenic associations of PCOS are insulin resistance and compensatory hyperinsulinemia (1, 2, 3). The hyperinsulinemia in turn stimulates ovarian androgen production. Several clinical studies have demonstrated that a reduction in the insulin level results in decreased ovarian androgen production (4, 5, 6).
Metformin is a biguanide used extensively in type 2 diabetes. It inhibits hepatic gluconeogenesis and increases peripheral insulin sensitivity and glucose uptake but does not cause hypoglycemia (6, 7, 8). The correction of the hyperinsulinemia by metformin in PCOS patients is accompanied by normalization of the elevated serum LH and ovarian androgen levels, leading to resumption of spontaneous ovulatory cycles, or responsiveness to ovulation induction by clomiphene citrate (CC) (1, 4, 5, 6, 8, 9). Clinical use of this agent for ovulation induction in CC-resistant PCOS patients has increased with little knowledge of the possible effect on early embryo development. We sought to assess whether metformin was embryotoxic using a mouse embryo model.
During controlled clinical trials, plasma metformin levels do not exceed 5 μg/mL, even at maximum doses (10). Metformin hydrochloride (N, N-dimethylimidodicarbonimidic diamide hydrochloride; Sigma, St. Louis, MO) was dissolved in human tubal fluid (HTF) media (Irvine Scientific, Santa Ana, CA) to give working concentrations of 5, 25, and 100 μg. The culture dishes containing 1 mL of media at each concentration were incubated for overnight equilibration at 37°C and 5% CO2.
Thawed two-cell mouse embryos (Embryotech, Wilmington, MA) were pooled and randomly distributed into the culture dishes containing the various concentrations of metformin. The control consisted of HTF media alone (group 1). Groups 2, 3, and 4 were supplemented with metformin (5, 25, and 100 μg/mL). There were 40 embryos in each group. The embryos were incubated in an atmosphere of 5% CO2 at 37°C for 72 hours. The blastocyst development rate (BDR) was then calculated by dividing the number of embryos reaching the blastocyst stage by the total number of embryos cultured.
The relationship between BDR and concentration was assessed with repeated measures logistic regression using generalized estimated equation (GEE) methodology with a compound symmetry correlation structure. The sample size was sufficient to detect whether a specific concentration reduced the odds of development by a factor of 2.5. Statistical significance was assessed using two-tailed P<.05. Statistical computations were performed with SAS version 8.1 (SAS Institute Inc, Cary, NC). . .


Oral contraceptive use and bone mineral density in premenopausal women:  cross-sectional, population-based data from the Canadian Multicentre Osteoporosis  Study

Jonathan D Adachi

McMaster University, Hamilton, ON, Canada

Abstract:
Background: Positive and negative effects on bone mineral density (BMD) have been described as a result of the premenopausal use of oral contraceptives (OCs); increased fracture rates have also been reported. This study assessed the relation between OC use and BMD in a population-based, 9-centre, national sample of women aged 25-45 years.

Methods: Premenopausal women who had been enrolled in the Canadian Multicentre Osteoporosis Study were classified as having ever been OC users (> or = 3 months) or as having never been OC users (0 to < 3 months). Data were obtained through extensive questionnaires and measuring of participants' weight, height and the BMD of lumbar vertebrae and the proximal femur.

Results: Of the sample of 524 women, whose mean age was 36.3 (standard deviation [SD] 5.9) years, 454 had used OCs; their mean age when they started using OCs was 19.8 (SD 3.5) years and the mean duration of use was 6.8 (SD 4.8) years. Women who had ever and those who had never used OCs showed no differences in age, age at menarche, parity, current calcium intake, exercise, body mass index (BMI), education, past irregular cycles or amenorrhea. OC users reported more alcohol and cigarette use and more use of medications to create regular cycles. Mean BMD values (adjusted for age, BMI and height) were 0.02-0.04 g/cm2 (that is, 2.3%-3.7%) lower in OC users, and were significantly lower in the spine and trochanter. The BMD of the spine in OC users was 1.03 (SD 0.12) g/cm2 versus 1.07 (SD 0.12) g/cm2 (95% confidence interval [CI] of difference -0.07 to -0.001) in those who had never used OCs. BMD was neither related to the duration of OC use nor to gynecological age at first use. Current and past users had similar BMD values.

Interpretation: National, population-based data show lower BMD values for the trochanter and spine in premenopausal women who have used OCs compared with those who have never used OCs.

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


Management of the extremely preterm infant: is the replacement of estradiol and progesterone beneficial?

Abstract: This review presents data to suggest that postnatal estradiol and progesterone replacement therapy may be beneficial in preterm infants. During pregnancy, maternal plasma levels of estradiol and progesterone increase up to 100-fold compared to the nonpregnant status. The fetus is also exposed to these increasing hormone levels. After delivery, estradiol and progesterone levels drop by a factor of 100 within 1 day. Whereas this is a physiological condition for an infant born at term, preterm delivery means withdrawal from the placental supply of these hormones at an earlier developmental stage. Seventy years ago, the idea was raised that preterm infants may benefit from the replacement of estrogens. Studies in which estrogen was injected subcutaneously showed only a slightly better bodyweight gain compared to placebo-treated controls and therefore routine use was not established. The effective treatment of postmenopausal osteoporosis with hormone replacement therapy led to a pilot study of estradiol and progesterone therapy to prevent osteopenia of prematurity. The highest median bone mineral accretion rate was found in the replacement group when the supplementation with calcium and phosphorus was also sufficient. None of the previous studies dealing with estrogen replacement controlled for achieved plasma levels of estradiol in the infants. In our controlled randomised pilot study with 30 preterm infants (15 in each group), we aimed to maintain intra-uterine plasma levels of estradiol and progesterone. Preterm infants with replacement of estradiol and progesterone for 6 weeks postnatally showed trends to higher bone mineral accumulation. In addition, a trend towards a lower incidence of chronic lung disease was found. Neurodevelopmental follow-up showed normal psychomotor development in infants given estradiol and progesterone, whereas the untreated infants (controls) showed a trend towards delayed development. Recent research emphasises that estradiol and progesterone may be important for brain development. Thus, while there is data indicating that postnatal estradiol and progesterone replacement therapy may be beneficial in preterm infants, experience with this new therapy is limited and extensive research is needed to address the potential benefits and to rule out adverse effects.


The influence of osteoporotic fractures on health-related quality of life in community-dwelling men and women across Canada

Canadian Multicentre Osteoporosis Study (CaMos) Research Group

Jerilynn C Prior

Vancouver Hospital and Health Sciences Centre

Abstract: Health-related quality of life (HRQL) was examined in relation to prevalent fractures in 4816 community-dwelling Canadian men and women 50 years and older participating in the Canadian Multicentre Osteoporosis Study (CaMos). Fractures were of three categories: clinically recognized main fractures, subclinical vertebral fractures and fractures at other sites. Main fractures were divided and analyzed at the hip, spine, wrist/forearm, pelvis and rib sites. Baseline assessments of anthropometric data, medical history, therapeutic drug use, spinal radiographs and prevalent fractures were obtained from all participants. The SF-36 instrument was used as a tool to measure HRQL. A total of 652 (13.5%) main fractures were reported. Results indicated that hip, spine, wrist/forearm, pelvis and rib fractures had occurred in 78 (1.6%), 40 (0.8%), 390 (8.1%), 19 (0.4%) and 125 (2.6%) individuals, respectively (subjects may have had more than one main fracture). Subjects who had experienced a main prevalent fracture had lower HRQL scores compared with non-fractured participants. The largest differences were observed in the physical functioning (-4.0; 95% confidence intervals (CI): -6.0, -2.0) and role-physical functioning domains (-5.8; 95% CI: -9.5, -2.2). In women, the physical functioning domain was most influenced by hip (-14.9%; 95% CI: -20.9, -9.0) and pelvis (-18.1; 95% CI: -27.6, -8.6) fractures. In men, the role-physical domain was most affected by hip fractures (-35.7; 95% CI: -60.4, -11.1). Subjects who experienced subclinical vertebral fractures had lower HRQL scores than those without prevalent fractures. In conclusion, HRQL was lower in the physical functioning domain in women and the role-physical domain in men who sustained main fractures at the hip. Subclinical vertebral fractures exerted a moderate effect on HRQL.


Chronobiological basis of female-specific mood disorders

Abstract: Women have twice the incidence of major depression compared with men. They are prone to develop episodes of depression during times of reproductive hormonal change at puberty, with use of oral contraceptives, during the premenstrual phase of the menstrual cycle, postpartum and during the perimenopause (see review: ). describes the variety of disturbances in biological rhythms observed in mood disorders. In this report, we describe the chronobiological disturbances observed in female-specific mood disorders, namely, premenstrual dysphoric disorder, pregnancy and postpartum depression and menopause. We hypothesize that changing reproductive hormones, by affecting the synchrony or coherence between components of the circadian system, may alter amplitude or phase (timing) relationships and thereby contribute to the development of mood disorders in predisposed individuals.

Neuropsychopharmacology : Official Publication of the American College of  Neuropsychopharmacology


Superovulation strategies for assisted reproductive technologies

Abstract: Assisted reproductive technologies (ART) pregnancy rates improve with the replacement of multiple embryos. The specific number of embryos to be transferred (typically between two and four) is based on a patient's age and past history and a morphologic assessment of embryo quality. Superovulation, with the goal of multifollicular recruitment and the harvest of multiple preovulatory oocytes, is therefore an integral aspect of in vitro fertilization and related techniques. Given the considerable interindividual variability in response to superovulation, the selection of an appropriate ovarian stimulation protocol is critical both for the safety and success of ART. Specific superovulation strategies have therefore been developed for treatment of abnormal response patients as well as for patients expected to manifest a "normal" response to ovulation inducing agents.


Avoidance of multiple pregnancies after ovulation induction by supernumerary preovulatory follicular reduction

Abstract:
OBJECTIVE: To evaluate the effect of supernumerary preovulatory follicular reduction as an approach to avoid multiple pregnancies in ovulation induction or superovulation cycles.

DESIGN: Retrospective study.

SETTING: Tertiary referral center.

PATIENT(S): In 26 cycles, 24 patients underwent ovulation induction or superovulation with either clomiphene citrate or hMG.

INTERVENTION(S): Selective follicle aspiration was performed before hCG administration.

MAIN OUTCOME MEASURE(S): Clinical pregnancy rate and numbers of multiple pregnancies.

RESULT(S): A mean number of 4.5 follicles with a diameter > or =15 mm and a mean number of 4.5 follicles with a diameter < or =14 mm were observed before hCG administration. A mean number of 2.3 follicles with a diameter > or =15 mm and a mean number of 1.8 follicles with a diameter < or =14 mm were aspirated before the hCG administration. Seven singleton pregnancies (26.9% per cycle) ensued from the treatment.

CONCLUSION(S): Aspiration of supernumerary follicles after ovulation induction or superovulation seems to be a valid approach to avoid multiple pregnancies without affecting pregnancy rate.


Efficacy of progesterone and progestogens in management of premenstrual syndrome: systematic review

Abstract:
OBJECTIVE: To evaluate the efficacy of progesterone and progestogens in the management of premenstrual syndrome.

DESIGN: Systematic review of published randomised, placebo controlled trials.

STUDIES REVIEWED: 10 trials of progesterone therapy (531 women) and four trials of progestogen therapy (378 women).

MAIN OUTCOME MEASURES: Proportion of women whose symptoms showed improvement with progesterone preparations (suppositories and oral micronised). Proportion of women whose symptoms showed improvement with progestogens. Secondary analysis of efficacy of progesterone and progestogens in managing physical and behavioural symptoms.

RESULTS: Overall standardised mean difference for all trials that assessed efficacy of progesterone (by both routes of administration) was -0.028 (95% confidence interval -0.017 to -0.040). The odds ratio was 1.05 (1.03 to 1.08) in favour of progesterone, indicating no clinically important difference between progesterone and placebo. For progestogens the overall standardised mean was -0.036 (-0.014 to -0.060), which corresponds to an odds ratio of 1.07 (1.03 to 1.11) showing a statistically, but not clinically, significant improvement for women taking progestogens.

CONCLUSION: The evidence from these meta-analyses does not support the use of progesterone or progestogens in the management of premenstrual syndrome.


Obstetric uses of intravenous immunoglobulin: successes, failures, and promises

Abstract: Intravenous immune globulin (IVIG) is approved for use in a number of conditions that may occur in obstetrical patients, including autoimmune thrombocytopenia and immune deficiency syndromes. IVIG also is widely used in obstetrics for nonapproved indications, such as fetal-neonatal alloimmune thrombocytopenia, antiphospholipid syndrome, and recurrent miscarriage. This review critically analyzes the use of IVIG for these indications based on the best available information. The authors conclude IVIG is effective in the management of fetal-neonatal alloimmune thrombocytopenia. IVIG appears promising as a treatment for severe fetal-neonatal alloimmune hemolysis due to antierythrocyte antibodies. A prospective multicenter trial should be undertaken. IVIG is no more effective than heparin and low-dose aspirin in the treatment of pregnancies complicated by antiphospholipid syndrome but has not been adequately evaluated in refractory cases. Finally, pending convincing studies, IVIG is not effective and should not be used for the management of recurrent miscarriage.

The Journal of Allergy and Clinical Immunology


Results of a 10 week community based strength and balance training programme to reduce fall risk factors: a randomised controlled trial in 65-75 year old women with osteoporosis

H A McKay

Departments of Human Kinetics, Medicine, Division of Endocrinology and Metabolism, and Human Nutrition, University of British Columbia, Vancouver, British Columbia, Canada.

Abstract:
Objective: To test the efficacy of a community based 10 week exercise intervention to reduce fall risk factors in women with osteoporosis.

Methods: Static balance was measured by computerised dynamic posturography (Equitest), dynamic balance by timed figure of eight run, and knee extension strength by dynamometry. Subjects were randomised to exercise intervention (twice weekly Osteofit classes for 10 weeks) or control groups.

Results: The outcome in 79 participants (39 exercise, 40 control) who were available for measurement 10 weeks after baseline measurement is reported. After confounding factors had been controlled for, the exercise group did not make significant gains compared with their control counterparts, although there were consistent trends toward greater improvement in all three primary outcome measures. Relative to the change in control subjects, the exercise group improved by 2.3% in static balance, 1.9% in dynamic balance, and 13.9% in knee extension strength.

Conclusions: A 10 week community based physical activity intervention did not significantly reduce fall risk factors in women with osteoporosis. However, trends toward improvement in key independent risk factors for falling suggest that a study with greater power may show that these variables can be improved to a level that reaches statistical significance.


Serum progesterone levels correlate with decreased cerebral edema after traumatic brain injury in male rats

Abstract: Previous animal research suggests that progesterone may have powerful neuroprotective effects in traumatic brain injury (TBI). This experiment tested the hypothesis that progesterone levels correlate with decreased cerebral edema in male rats with bilateral medial frontal cortex injuries. Three groups of male Sprague-Dawley rats were used: injured given progesterone (4 mg/kg), injured given vehicle (oil), and uninjured controls given vehicle. Progesterone or vehicle was administered intraperitoneally at 1, 6, and 24 h postinjury. At 48 h postinjury, the rats were killed, brains extracted, and assayed for edema. Percent difference in water content of the area surrounding the lesion was compared to posterior cortex. A strong inverse relationship was found between serum progesterone levels and percent cerebral edema; the higher the progesterone levels, the lower the percent edema. Both progesterone and oil-treated animals had some edema compared to sham-operated controls. The brains of the injured animals given control solution were higher in water content than either the uninjured group or injured progesterone-treated rats 48 h postinjury. These findings confirm that progesterone significantly decreases cerebral edema after TBI in adult male subjects.


Mid-trimester endovaginal sonography in women at high risk for spontaneous preterm birth

National Institute of Child Health and Human Development, Maternal-Fetal Medicine Units Network

D McNellis

Eunice Kennedy Shriver National Institute of Child Health and Human Development

Abstract:
CONTEXT: Although shortened cervical length has been consistently associated with spontaneous preterm birth, it is not known when in gestation this risk factor becomes apparent.

OBJECTIVE: To determine whether sonographic cervical findings between 16 weeks' and 18 weeks 6 days' gestation predict spontaneous preterm birth and whether serial evaluations up to 23 weeks 6 days' gestation improve prediction in high-risk women.

DESIGN, SETTING, AND

PARTICIPANTS: Blinded observational study performed between March 1997 and November 1999 at 9 university-affiliated medical centers in the United States in 183 women with singleton gestations who previously had experienced a spontaneous birth before 32 weeks' gestation.

OBSERVATION: Certified sonologists performed 590 endovaginal sonographic examinations at 2-week intervals. Cervical length was measured from the external os to the functional internal os along a closed endocervical canal. Funneling and dynamic cervical shortening were also recorded.

MAIN OUTCOME MEASURE: Spontaneous preterm birth before 35 weeks' gestation, analyzed by selected cutoff values of cervical length.

RESULTS: Forty-eight women (26%) experienced spontaneous preterm birth before 35 weeks' gestation. A cervical length of less than 25 mm at the initial sonographic examination was associated with a relative risk (RR) for spontaneous preterm birth of 3.3 (95% confidence interval [CI], 2.1-5.0; sensitivity = 19%; specificity = 98%; positive predictive value = 75%). After controlling for cervical length, neither funneling (P =.24) nor dynamic shortening (P =.054) were significant independent predictors of spontaneous preterm birth. However, using the shortest ever observed cervical length on serial evaluations, after any dynamic shortening, the RR of a cervical length of less than 25 mm for spontaneous preterm birth increased to 4.5 (95% CI, 2.7-7.6; sensitivity = 69%; specificity = 80%; positive predictive value = 55%). Compared with a single cervical measurement at 16 weeks' to 18 weeks 6 days' gestation, serial measurements at up to 23 weeks 6 days significantly improved the prediction of spontaneous preterm birth in a receiver operating characteristic curve analysis (P =.03).

CONCLUSIONS: Cervical length assessed by endovaginal sonography between 16 weeks' and 18 weeks 6 days' gestation, augmented by serial evaluations, predicts spontaneous preterm birth before 35 weeks' gestation in high-risk women.


Treating mental illness in lactating women

Abstract: A high prevalence of psychiatric illness has been noted in the postpartum period. Recent research looks to the potential effects of maternal illness during this period on child development. With the promotion of breast feeding for well-documented medical benefits, there has been increasing attention to the potential effects on the infant of exposure to medication via breast milk. This article reviews the current literature on the secretion of psychotropic medication into breast milk, and any known negative effects. The shortcomings of these studies are highlighted, and recommendations to the clinician are given within the limitations of the current state of knowledge. The World Health Organization (WHO) has estimated that depression will be 1 of the 2 major illness burdens confronting the world by 2020. The incidence of depression is 2-fold higher in women than in men, and the average age at onset is 25 years. These facts combined with the noted risk of a marked increase in psychiatric illness postpartum have serious implications. Depression occurring at this time can present with depressed mood, anxiety, and difficulties coping with the infant. Suicide, although not more common in depression, is at the severe end of the spectrum in those with puerperal psychosis and bipolar disorder. The morbidity associated with depression is not confined to women suffering from it; there are also potential negative effects of maternal depression on child development, on older children, and on the woman's partner. These effects include impaired bonding and cognitive and behavioral delays in the infant and difficulties in childhood. Moreover, the increased use of antidepressants in the Western world in combination with the strong promotion of breast feeding also has implications for the dependent infant. What do we know? And, what are the risks?


Metformin directly inhibits androgen production in human thecal cells

W E Rainey

The University of Texas Southwestern Medical Center

G R Attia

Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235-9032, USA.

Abstract:
OBJECTIVE: To examine the direct effect of metformin on thecal cell androgen production.

SETTING: Basic science research laboratory, University of Texas Southwestern, Dallas, Texas.

INTERVENTION(S): Human ovarian theca-like tumor cells were treated with various concentrations of metformin in the presence and absence of forskolin for 48 hours.

MAIN OUTCOME MEASURE(S): Media were collected, and radioimmunoassay (RIA) for progesterone, 17 alpha-hydroxyprogesterone (17OHP), androstenedione, and testosterone was performed. The effect of metformin on the expression of various enzymes involved in theca cell steroidogenesis was examined.

RESULT(S): Metformin (50 microM and 200 microM) significantly inhibited androstenedione production from both forskolin-stimulated and unstimulated theca cells. Testosterone production was also significantly inhibited in forskolin-treated cells in the presence of 200 microM of metformin-treated compared with forskolin-only-treated cells. Western blot analysis revealed that metformin significantly inhibited the expression of steroidogenic acute regulatory (StAR) protein and 17 alpha-hydroxylase (CYP17) expression in cells stimulated with forskolin compared with forskolin treatment alone. There was no significant change in either 3beta-hydroxysteroid dehydrogenase (3 beta HSD) or cholesterol side-chain cleavage (CYP11A1) protein expression. Northern analysis revealed a significant decrease in the expression of CYP17 mRNA in forskolin-stimulated cells treated with metformin (200 microM) compared with forskolin-only-treated cells, however, there was no significant change in steroidogenic acute regulatory protein mRNA expression.

CONCLUSION(S): Our results suggest that metformin may have a direct effect on thecal cells' androgen production.


Diastolic dysfunction and increased serum homocysteine concentrations may contribute to increased cardiovascular risk in patients with polycystic ovary syndrome

H Yarali

Department of Obstetrics and Gynecology, Faculty of Medicine, Hacettepe University, Ankara, Turkey. yarali@ada.net.tr

Abstract:
OBJECTIVE: To assess cardiac flow parameters in patients with polycystic ovary syndrome (PCOS).

DESIGN: A prospective case-control study.

SETTING: University-based hospital.

PATIENT(S): Thirty consecutive patients with PCOS were enrolled. Thirty women with regular menstrual cycles served as the controls.

INTERVENTION(S): Systolic and diastolic function parameters were assessed by standard two-dimensional and M-mode echocardiography. Insulin sensitivity was evaluated by a standard 75-g oral glucose tolerance test and area-under-curve insulin analysis. Serum hormones, lipid profile, homocysteine, vitamin B(12), folate, fibrinogen, uric acid, and plasminogen activator inhibitor-I concentrations were measured.

MAIN OUTCOME MEASURE(S): Systolic and diastolic function parameters, insulin sensitivity and serum homocysteine levels.

RESULT(S): The mean serum homocysteine and uric acid concentrations were significantly higher in the PCOS group. Patients with PCOS had significant hyperinsulinemia. All systolic function parameters were comparable between the two groups. However, patients with PCOS had significantly lower peak mitral flow velocity in early diastole and significantly lower ratio between the early and late peak mitral flow velocities and also had significantly longer isovolumic relaxation time, reflecting a trend for nonrestrictive-type diastolic dysfunction. The area-under-curve insulin correlated positively with peak mitral flow velocity in late diastole (r = 0.375). The mean cholesterol/high-density lipoprotein ratio correlated negatively with mean mitral flow velocity in early diastole (E) peak (r = -0.474). The mean fasting insulin level correlated negatively with mean E/A ratio (r = -0.387).

CONCLUSION(S): Diastolic dysfunction and increased serum homocysteine concentrations may contribute to increased cardiovascular disease risk in patients with PCOS.


Preterm delivery: a public health perspective

Abstract: And his daughter‐in‐law, the wife of Phinehas, was pregnant near to giving birth, and got to hear the report that the ark of the true God was captured and that her father‐in‐law and her husband had died. At that she bowed herself and began giving birth, because her pangs came unexpectedly upon her.


A randomized trial of nurse specialist home care for women with high-risk pregnancies: outcomes and costs

Abstract:
OBJECTIVE: To examine prenatal, maternal, and infant outcomes and costs through 1 year after delivery using a model of prenatal care for women at high risk of delivering low-birth-weight infants in which half of the prenatal care was provided in women's homes by nurse specialists with master's degrees.

STUDY DESIGN: Randomized clinical trial.

PATIENTS AND

METHODS: A sample of 173 women (and 194 infants) with high-risk pregnancies (gestational or pregestational diabetes mellitus, chronic hypertension, preterm labor, or high risk of preterm labor) were randomly assigned to the intervention group (85 women and 94 infants) or the control group (88 women and 100 infants). Control women received usual prenatal care. Intervention women received half of their prenatal care in their homes, with teaching, counseling, telephone outreach, daily telephone availability, and a postpartum home visit by nurse specialists with physician backup.

RESULTS: For the full sample, mean maternal age was 27 years; 85.5% of women were single mothers, 36.4% had less than a high school education, 93.6% were African American, and 93.6% had public health insurance, with no differences between groups on these variables. The intervention group had lower fetal/infant mortality vs the control group (2 vs 9), 11 fewer preterm infants, more twin pregnancies carried to term (77.7% vs 33.3%), fewer prenatal hospitalizations (41 vs 49), fewer infant rehospitalizations (18 vs 24), and a savings of more than 750 total hospital days and $2,496,145 [corrected].

CONCLUSION: This model of care provides a reasoned solution to improving pregnancy and infant outcomes while reducing healthcare costs.


Chronological aspects of ultrasonic, hormonal, and other indirect indices of ovulation

Abstract:
OBJECTIVE: To improve prediction of ovulation in normal cycles.

DESIGN: Collection of women's characteristics and their menstrual cycles. Monitoring and analysis of time relationships between several indicators of ovulation: transvaginal ultrasonography, cervical mucus, basal body temperature, urinary luteinising hormone, and ratio of urinary oestrogen to progesterone metabolites.

SETTING: Each of eight natural family planning clinics was to study 12 women for at least three cycles.

POPULATION: One hundred and seven normally fertile and cycling women aged 18 to 45.

METHODS: Daily measurements of urinary luteinising hormone, follicle stimulating hormone, oestrone-3-glucuronide and pregnanediol-3alpha-glucuronide. Basal body temperature recording and cervical mucus checking. Transvaginal ultrasound examination of the ovaries.

MAIN OUTCOME MEASURES: Delays between the expected day of ovulation according to the luteinising hormone peak or to ultrasound evidence and the expected days according to the other indices of ovulation.

RESULTS: Ultrasonography was able to show evidence of ovulation in 283 out of 326 cycles. The average time lag between luteinising hormone peak and ultrasound evidence was less than one day (+0.46) but premature and late luteinising hormone-expected date of ovulation were observed in nearly 10% and 23% of cycles, respectively. Basal body temperature rise was observed in 98% of cycles. Cervical mucus peak symptom, rapid drop in the ratio of urinary metabolites, and luteinising hormone initial rise were all close to ultrasonographic evidence in more than 72% of cycles.

CONCLUSIONS: For accuracy and practical reasons, the cervical mucus peak symptom, the ratio of urinary metabolites and luteinising hormone initial rise might be better indices of ovulation than the luteinising hormone peak.

BJOG : an International Journal of Obstetrics and Gynaecology


Naltrexone effect on pulsatile GnRH therapy for ovulation induction in polycystic  ovary syndrome: a pilot prospective study

Abstract: The aim of the present study was to analyze the opioid influence on LH pulsatility in polycystic ovary syndrome (PCOS) patients and to evaluate the effectiveness of a long-term opioid antagonist (naltrexone) treatment in improving the pulsatile GnRH therapy which is successful in this syndrome. Ten obese women affected by PCOS participated in the study. Patients were hospitalized during the early follicular phase and underwent an oral glucose tolerance test (OGTT) with 75 g of glucose and a pulse pattern study followed by a GnRH test (100 pg i.v.). All patients were then treated for ovulation induction with pulsatile administration of GnRH (5 microg/bolus every 90 min). Since pregnancies did not occurr in any patient, after spontaneous or progestin-induced menstrual cycles, all patients received naltrexone at a dose of 50 mg/day orally for 8 weeks and during treatment repeated the basal protocol study and the ovulation induction cycle with the same modalities. The naltrexone treatment significantly reduced the insulin response to OGTT and the LH response to GnRH bolus, whereas it did not affect the FSH and LH pulsatility patterns. Concerning the ovulation induction by pulsatile GnRH, naltrexone treatment was able to improve, although not significantly, the ovulation rate (60% pre-treatment vs 90% post-treatment). Furthermore, the maximum diameter of the dominant follicle and the pre-ovulatory estradiol concentration were higher after long-term opioid blockade (follicular diameter 19.5+/-1.76 mm pre-treatment vs 21.6+/-2.19 mm post-treatment, p<0.001; maximum estradiol level 728.7+/-288.5 pmol/l pre-treatment vs 986.4+/-382.1 pmol/l post-treatment, p<0.05). During the naltrexone-pulsatile GnRH co-treatment two pregnancies occurred. In conclusion, our data show that naltrexone-pulsatile GnRH co-treatment is able to improve the ovarian responsiveness to ovulation induction in obese PCOS patients when compared to pulsatile GnRH alone. This action seems to be related to a decrease of insulin secretion. Further randomized studies should be performed in order to obtain significant conclusions on the possible clinical application.

Journal of Endocrinological Investigation


[Hormone replacement therapy of menopause, heart and blood vessels]

Abstract: The incidence of coronary heart disease (CHD) is lower in premenopausal women than in men and post-menopausal women of the same age. The higher CHD rate after menopause is currently attributed to estrogen deficiency: many epidemiological (case-control and prospective) studies have reported a reduced risk (0.5-0.63) of CHD in post-menopausal women receiving hormone replacement therapy (HRT). Moreover, estrogens have multiple effects that would be expected to be cardioprotective, including favorable changes in lipids, endothelial function, vascular reactivity and blood flow. However, the observational studies are subject to several biases that could falsely elevate the apparent benefit of estrogens: women taking estrogens tend to be wealthier, more educated and healthier than untreated women. The american HERS (Heart and Estrogen-progestin Replacement Study; 2.763 women) is a large multicenter randomized study of secondary prevention, designed to evaluate the efficacy of HRT. Results are disappointing, since no reduced risk was observed, and the risk of CHD was even higher in women receiving HRT during the first year: 1.52 (CI 95%: 1.01-2.29). In HERS study, the treatments consisted of conjugated equine estrogens and the synthetic progestin medroxyprogesterone acetate (MPA) which are rarely used in Europe. Indeed, the effects of HRT are not equivalent depending on the dose, the route of administration, the type of progestogen. It should be emphasized that MPA, contrarily to progesterone, inhibits the beneficial effect of estrogens on lipids and experimental atherosclerosis. The route of administration of estrogens is also involved: estrogens alter hemostasis factors, and when orally administered, they have a first pass liver effect, which favors hypercoagulability. It is therefore urgent that Europeans undertake a European "HERS study" in order to investigate the possible beneficial effect of non oral estrogens (gel or patch) associated with natural progesterone.

Archives Des Maladies Du Coeur Et Des Vaisseaux


Survival, morbidity, and resource use of infants of 25 weeks' gestational age or less

Abstract:
OBJECTIVE: The objective of this study was to examine survival, morbidity, and resource use in a large cohort of extremely preterm infants.

STUDY DESIGN: We examined all (n = 754) neonatal intensive care unit admissions born at < or =25 weeks' gestation and inborn deliveries (n = 949) between 22 and 25 weeks' gestation at 17 Canadian neonatal intensive care units.

RESULTS: The overall survival rate was 63%, with a range from 14% at 22 weeks' gestation to 76% at 25 weeks' gestation. There was a high incidence of chronic lung disease (33%-51%), > or =grade 3 intraventricular hemorrhage (0%-16%), necrotizing enterocolitis (0%-14%), > or =stage 3 retinopathy of prematurity (27%-55%), nosocomial infection (25%-39%), and multiple gestation (18%-46%). Extremely preterm infants comprise 4% of neonatal intensive care unit admissions but account for 22% of deaths, 20%-60% of major morbidities, 11% of patient days, and 10%-35% of major procedures. Outborn infants had a higher incidence of chronic lung disease, severe retinopathy of prematurity, and intraventricular hemorrhage.

CONCLUSION: Extremely preterm infants have a high incidence of mortality and morbidity and consume disproportionate amounts of neonatal intensive care unit resources.

American Journal of Obstetrics and Gynecology


The role of semen in induction of maternal immune tolerance to pregnancy

Abstract: Successful pregnancy requires a state of maternal immune 'tolerance' to accommodate antigens expressed by the conceptus. Implantation failure and placental pathologies largely reflect insufficiencies in maternal immune adaptation, but progress in devising therapeutic strategies to treat these conditions is stalled because the mechanisms underlying the induction and maintenance of maternal tolerance are unknown. Increasingly, clinical and experimental data support the proposal that insemination has consequences for the reproductive process beyond delivery of male gametes. An emerging hypothesis, based mainly on clinical observations and experiments in mice, is that insemination is causally linked to the activation and expansion of populations of lymphocytes mediating forms of 'active' immune tolerance in the implantation site. This review examines existing evidence for a role for semen in the immunology of pregnancy, highlighting the limitations of our existing knowledge and the prospects for future research and its clinical application.


Comparison of several one-step home urinary luteinizing hormone detection test kits to OvuQuick

Abstract:
Objective: To compare clinical accuracy and ease of use for several of the new rapid one-step home urinary LH detection kits compared with the preexisting OvuQuick brand LH detection kit (designated as the standard).
Design: Prospective cohort study.
Setting: University-based infertility clinic. PATIENT(S): All women undergoing intrauterine inseminations at the clinic, regardless of infertility diagnosis, were offered enrollment during a 28-month study period. INTERVENTION(S): Each participant was supplied three one-step test kits (OvuQuick One-Step, ClearPlan Easy, and SureStep) in addition to a multistep OvuQuick test kit and instructed to run the tests in parallel on the same urine sample and to record the results. Urine testing was performed every 12 hours, beginning 3 days before the anticipated onset of an LH surge, and continued with the one-step kits every 12 hours for 48 hours after the surge was first detected by OvuQuick. Subjects also completed questionnaires evaluating the use of each test kit. MAIN OUTCOME MEASURE(S): Correlation of LH surge detection by one-step kits in comparison to surge detection by OvuQuick. Satisfaction and ease of use questionnaires. RESULT(S): Sixty-three volunteers returned useable data, from which 81 evaluable cycles were analyzed. The majority of patients found the newer one-step kits to be easier to use and less time consuming than OvuQuick. The three one-step kits detected the LH surge within +/- one testing period (+/-12 hours) of detection by OvuQuick 68%-84% of the time. OvuQuick One-Step, with modified instructions allowing for an equal color intensity in the test and reference areas, had the highest correlation with OvuQuick (84%). However, with a study power (alpha = 0.05, beta = 0.10) sufficient to detect a 10% difference between Ovuquick and each one-step kit, all one-step kits were statistically equivalent to each other. There was no cycle in which a one-step kit detected a positive LH surge but OvuQuick did not. CONCLUSION(S): One-step urinary LH kits are easier for patients to use than a multistep home urinary LH kit and have reasonable correlation with the multistep kit when used clinically for timing artificial inseminations.


A prospective randomized study comparing intramuscular progesterone and 17alpha-hydroxyprogesterone caproate in patients undergoing in vitro fertilization-embryo transfer cycles

Abstract:
OBJECTIVE: To compare the effectiveness of i.m. P and 17alpha-hydroxyprogesterone caproate (17-HPC) for luteal phase support, in patients undergoing IVF-ET cycles.

DESIGN: Prospective, randomized study.

SETTING: Patients undergoing IVF-ET in our Centers.

PATIENT(S): The inclusion criteria were the use of GnRH down-regulation and aged <40 years.

INTERVENTION(S): A total of 300 cycles were randomly treated with either 17-HPC (341 mg every 3 days) or P (50 mg daily).

MAIN OUTCOME MEASURE(S): The outcomes of IVF in both study groups were evaluated for biochemical pregnancy, miscarriage, clinical pregnancy, and ongoing pregnancy.

RESULT(S): No difference was found in the main outcome parameters considered.

CONCLUSION(S): Although the results of the study encourage the use of 17-HPC for luteal phase support in patients undergoing IVF-ET program, more studies are necessary to support the hypothesis that it can replace i.m. P-in-oil.


Efficacy of clomiphene citrate and cyclofenil for infertile women with normal ovulatory cycles

Abstract:
Despite the widespread use of clomiphene citrate (CC) for ovulation induction, the pregnancy rates (PRs) in women who take CC are less than expected based on ovulation rates. The causes of this discrepancy between the PRs and ovulation rates have been explained by the antiestrogenic effects on cervical mucus and endometrial differentiation (1). Despite these adverse effects, CC therapy is so simple and safe that it is widely administered even to normally ovulatory women in the expectation of inducing multiple ovulation and increasing the chances of conception.
On the other hand, cyclofenil, which has been reported to exert less antiestrogenic activity than CC (2), is also used to treat infertile women with not only anovulatory cycles but normal ovulatory cycles. The purpose of this study was to assess whether administration of CC or cyclofenil to women with normal ovulatory cycles is beneficial.
One hundred fifty-five normally ovulatory women who received treatment for infertility at Shiga University of Medical Science from June 1998 to June 1999 were recruited for this study. Patients with ovulatory disorders, such as irregular cycles, hypothalamic or pituitary amenorrhea, polycystic ovary syndrome, premature ovarian failure, and hyperprolactinemia, were excluded from the study. Patients with bilateral tubal obstruction or azoospermia were also excluded.
Administration of CC or cyclofenil was withheld for a period of 3 months after the first visit while the timing of coitus was advised. Patients were advised to have sexual intercourse within 24 hours after confirmation of a positive urinary LH with a urinary LH surge detection kit (Gold-sign LH, Morinaga Nyugyo, Tokyo, Japan).
Then the patients who did not conceive were sequentially allocated to three groups: a CC-treated group, a cyclofenil-treated group, and a group with no administration. Briefly, the first patient enrolled in the study was assigned to a CC-treated group, the second patient was assigned to a cyclofenil-treated group, and the third patient was assigned to a group with no administration. Then the fourth patient was assigned to the CC-treated group, and so forth.


A new ultrasound criterion for the diagnosis of polycystic ovary syndrome: the ovarian stroma/total area ratio

Abstract:
OBJECTIVE: To evaluate whether some ultrasound parameters of ovarian morphology can discriminate between control women and patients with polycystic ovary syndrome (PCOS).

DESIGN: Retrospective data analysis.

SETTING: Volunteers women in an academic research environment.

PATIENT(S): Eighty amenorrheic or oligomenorrheic women and 30 normal ovulatory control participants.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): We evaluated ovarian volume, area, stroma, and the stroma/total area (S/A) ratio by use of transvaginal pelvic ultrasound; and we assayed serum levels of gonadotropin, androgen, and estradiol during the early follicular phase (days 2 to 5) of the menstrual cycle in regularly cycling controls and on a random day in amenorrheic patients.

RESULT(S): Patients with PCOS showed significantly higher ovarian volume, area, stroma, and mean S/A ratio when compared to multifollicular and control groups. Cut-off values have been defined for ovarian volume (13.21 mL), area (7.00 cm2), stroma (1.95 cm2), and S/A ratio (0.34). The sensitivity for PCOS diagnosis was 21%, 4%, 62%, and 100%, respectively. The S/A ratio showed the most significant correlation with the androgen levels.

CONCLUSION(S): The evaluation of the S/A ratio can differentiate between PCOS and control or multifollicular women with both a sensitivity and a specificity of 100%. Furthermore, this ultrasound parameter is strictly related to hormonal milieu and to anthropometric characteristics.


A prospective controlled study of karyotyping for 430 consecutive babies conceived through intracytoplasmic sperm injection

Abstract:
OBJECTIVE: To compare the karyotype of babies conceived through ICSI with that of naturally conceived babies.

DESIGN: Prospective controlled study.

SETTING: The Egyptian IVF-ET Center, Cairo, Egypt.

PATIENT(S): Four hundred and thirty babies conceived through ICSI and 430 babies conceived naturally.

INTERVENTION(S): ICSI and karyotyping.

MAIN OUTCOME MEASURE(S): Abnormal karyotype.

RESULT(S): Four hundred and thirty consecutive babies conceived through ICSI who were delivered in one hospital had 15 abnormal karyotypes (3.5%). Of the 15 babies, 7 were of female phenotype and 8 of male phenotype. Six babies had sex chromosome anomalies, 8 had autosomal anomalies, and 1 had combined sex chromosome and autosomal anomalies. A control group of 430 consecutive babies conceived naturally who were delivered in one hospital had no abnormal karyotype. The difference between the two groups was significant (P<.001).

CONCLUSION(S): ICSI carries a small but significant increased risk of abnormal karyotyping to the offspring. This risk appears to be equally distributed between autosomal and sex chromosome anomalies.


Psychological correlates of functional hypothalamic amenorrhea

Abstract:
OBJECTIVE: To determine whether mood, attitudes, or symptoms of disordered eating discriminated women with functional hypothalamic amenorrhea (FHA) from those with organic causes of amenorrhea and eumenorrhea.

DESIGN: Cross-sectional comparison of women with FHA, women with organic amenorrhea, and eumenorrheic control women.

SETTING: Clinical research center in an academic medical institution.

PATIENT(S): Seventy-seven women > or =18 years old with time since menarche > or =5 and < or =25 years were recruited by advertisement.

INTERVENTION(S): Ovulation was confirmed in eumenorrheic control women. Causes of anovulation were carefully documented in amenorrheic participants and LH pulse profiles were obtained to document the diagnosis of FHA. All participants were interviewed and completed questionnaires.

MAIN OUTCOME MEASURE(S): Self-report measures of dysfunctional attitudes, coping styles, and symptoms of depression and eating disorders.

RESULT(S): Women with FHA reported more depressive symptoms and dysfunctional attitudes than did eumenorrheic women, but not significantly more than women with organic amenorrhea. However, women with FHA reported significantly more symptoms of disordered eating than did either anovulatory or ovulatory women.

CONCLUSION(S): The findings are consistent with the hypothesis that FHA is precipitated by a combination of psychosocial stressors and metabolic challenge.


Dietary restraint, exercise, and bone density in young women: are they related?

Susan I Barr

Vancouver Hospital and Health Sciences Centre

Abstract:
Purpose: Women with high scores for dietary restraint have been found to have higher 24-h urinary cortisol excretion and a higher prevalence of subclinical ovulatory disturbances, both of which may be risk factors for bone loss. The purpose of this study was to explore relationships between dietary restraint and bone health in regularly menstruating young women.

Methods: 62 women (age: 21.7 +/- 2.5 yr) had body composition and total body and lumbar spine bone mineral density (BMD) and content (BMC) assessed using dual-energy x-ray absorptiometry. Dietary restraint was assessed using the restraint subscale from the Three-Factor Eating Questionnaire: 29 women had low restraint (LR; restraint score 0--5), 33 had high restraint (HR; restraint score 13--21). Exercise (h x wk(-1)) was assessed by questionnaire on two occasions.

Results: LR and HR women were similar in age and body composition (fat mass = 15.0 +/- 4.7 kg, lean mass = 40.9 +/- 4.9 kg), but HR women exercised more (3.4 +/- 1.7 vs 2.2 +/- 1.8 h x wk(-1), P < 0.05). Exercise was correlated with BMD and BMC, and when it was included as a covariate, total body BMC was significantly lower in HR than LR women. In multiple regression analysis, weekly hours of exercise and restraint score were significant predictors of total body BMD and BMC.

Conclusion: The observations of this cross-sectional study suggest that high levels of cognitive dietary restraint, or associated factors such as higher cortisol, may attenuate the positive effects of exercise on bone in young women.

Medicine and Science in Sports and Exercise


Expert in fertility appreciation: the Creighton Model practitioner

Abstract: The Creighton Model system of natural family planning (NFP) is useful in achieving pregnancy, avoiding pregnancy, and detecting some gynecologic disorders. NFP practitioners support the client in using NFP. Because the effectiveness of NFP is related to the teaching process and to teacher expertise, clients choosing NFP may be best served by referral to a certified NFP practitioner for instruction.

Journal of Obstetric, Gynecologic, and Neonatal Nursing : JOGNN


Outcome in the second year of life after in-vitro fertilisation by intracytoplasmic sperm injection: a UK case-control study

Abstract:
BACKGROUND: There have been reports suggesting that children born after in-vitro fertilisation by intracytoplasmic sperm injection (ICSI) are at increased risk of neurodevelopmental delay. We have undertaken a case-control study of this issue.

METHODS: We studied 208 singleton children conceived by ICSI and a control group of 221 normally conceived singleton children. Children were recruited from 22 fertility centres and local nurseries throughout the UK. Controls were selected to match cases as closely as possible for social class, maternal educational attainment, region, sex, and race. The primary outcome measure was neurodevelopmental scoring; secondary measures were perinatal outcomes, postnatal health, and congenital abnormalities. A single examiner assessed all the children.

FINDINGS: A follow-up rate of 90% for the ICSI group was achieved at a mean age of 17 months. No difference between the study children and controls was found in mean neurodevelopmental scores (98.08 [SD 10.93] vs 98.69 [9.99]) or any subscales on the Griffiths' scales of mental development. Perinatal outcome was similar apart from a higher rate of caesarean section (73 [35.1%] vs 53 [24.0%], p=0.015) and a lower mean birthweight (3163 [SD 642] vs 3341 [606] g, p=0.013) in the study group. Rates of major congenital abnormality were also similar overall (ten [4.8%] study vs ten [4.5%] control), although there were significantly more congenital anomalies among children born to fathers with oligozoospermia than in other children.

INTERPRETATION: This population study did not show any significant difference between children conceived after ICSI and their naturally conceived peers in terms of physical health and development.


Blood loss following noncomplicated transvaginal oocyte retrieval for in vitro fertilization

Abstract:
Transvaginal ultrasonic follicle puncture has now become the method of choice for oocyte retrieval among most in vitro fertilization (IVF) units. The procedure, which involves puncture then aspiration of ovarian follicles, inevitably results in damage to the fine vascular network of blood vessels on the ovarian surface and theca interna layer, and tends to produce varying degrees of blood loss. The transvaginal ultrasonically guided retrieval of oocytes can be considered noncomplicated when the procedure does not result in injury to iliac vessels, trauma to pelvic viscera, or iatrogenic pelvic infections (1, 2), which would necessitate laparoscopy and or laparotomy. The aim of our study was to quantify the amount of blood loss that should be considered “normal” after noncomplicated transvaginal ultrasonically guided retrieval of oocytes, to characterize the factors that are related to the amount of blood loss, and to identify the patients who have the highest risk of hemorrhage.
Before beginning our study, we performed a power analysis of potential participants. We established the sample size after evaluating the number of women of fertile age in our area, and we used the previous years’ data to calculate the prevalence of sterility problems and the percentage of women who had undergone in vitro fertilization. Thus, our prospective study was based on a sample of 220 women, 25 to 42 years old, who underwent assisted reproduction from January 1998 to May 1999. We excluded the women who had mild or severe ovarian hyperstimulation syndrome or thrombocytopenia, those who were taking anticoagulant drugs, and those who were overweight (body mass index 25 to 30) or obese (body mass index greater than 30). The study was approved by the local hospital ethics committee and all of the participants gave written informed consent.


Distribution of topical medication in the human vagina as imaged by magnetic resonance imaging

Kurt T. Barnhart

University of Pennsylvania Health System

Abstract:
OBJECTIVE: To assess the use of magnetic resonance imaging (MRI) to determine the varying distribution of a vaginally placed gel over time and with different levels of patient activity.

DESIGN: Prospectives interventional trial.

SETTING: University medical center.

PATIENT(S): One nulliparous volunteer with normal menstrual cycles and no gynecologic disease who underwent seven MRI scans of the pelvis.

INTERVENTION(S): Five mL of a commercially available topical spermicide was mixed with gadolinium-chelate magnetic resonance contrast material and introduced with a standard applicator. T1-weighted three-dimensional MRI was done to assess the distribution of the gel.

MAIN OUTCOME MEASURE(S): Gel thickness and distribution.

RESULT(S): The initial bolus of gel was delivered into the upper portion of the vagina, above the urogenital diaphragm. Thereafter, it spread into the vaginal fornices and "flattened" to cover the lateral aspects of the vagina. Without ambulation, the majority of spread was confined to the upper vagina. With ambulation and longer elapsed time, the gel spread further in the upper vagina and into the lower vagina, and significant vaginal surface coverage increased significantly.

CONCLUSION(S): Magnetic resonance imaging can be used to monitor the spread of vaginally placed products and to evaluate coverage of topical drugs used for prevention and treatment, including those used for HIV prophylaxis.