To determine whether a new monophasic oral contraceptive containing drospirenone/ethinyl estradiol reduces premenstrual symptoms. 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. 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. An oral contraceptive containing drospirenone/ethinyl estradiol may reduce the premenstrual symptoms of negative affect, water retention and increased appetite.
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).
EndometriosisPrevalence and Risk FactorsDisease BurdenDisease Prevalence Studies
Center for Disease Control and Prevention, 2002·PsycEXTRA Dataset
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.
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.
Fertility AwarenessCalendar/Rhythm MethodInternational PerspectivesFocus Group Studies
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.
Menstrual CyclePMDD and Depression RiskPremenstrual Dysphoric DisorderPMDD Diagnostic Validity
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.
PregnancySpontaneous Abortion PreventionLuteal Function and PregnancyPrematurity and IUGR Prevention
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. 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. 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. In the group of VLBW infants the PCT level within 72 h of delivery was markedly increased in patients with chorioamnionitis. T and CRP, PCT appears to be a more sensitive marker of neonatal sepsis.
Contraception/ComparisonLuteal Phase SupportProgesterone SupplementationRoute of Administration
To compare the efficacy of Crinone 8% intravaginal progesterone gel vs. IM progesterone for luteal phase and early pregnancy support after IVF-ET. Randomized, open-label study. 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.
This study examined changes in the luteal vasculature throughout the menstrual cycle and during simulated pregnancy with human chorionic gonadotrophin (HCG) in the human. 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. 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. Luteal rescue with HCG is associated with a second wave of angiogenesis and vascular stabilization.
Reproductive EndocrinologyLuteal Phase SupplementationLuteal Phase SupportPreclinical Pregnancy Loss
Kaider AS et al., 2001·Early Pregnancy (Cherry Hill)
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.
Gonzales GF et al., 2001·Asian journal of andrology
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. 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. 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. Maca improved sperm production and sperm motility by mechanisms not related to LH, FSH, PRL, T and E2.
Perimenopause/MenopausePerimenopausal Bone LossProgesterone DeficiencyOvulatory Disturbances
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.
To review validation studies of the Edinburgh Postnatal Depression Scale (EPDS). 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%. Eighteen validation studies were identified. The study design varied between studies. The sensitivity and specificity 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. 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.
Gleicher N et al., 2001·Early Pregnancy (Cherry Hill)
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.
To determine the metabolic and reproductive effectiveness of rosiglitazone in polycystic ovary syndrome (PCOS). Case report. 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.
PCOSIn Vitro MaturationIn Vitro Oocyte MaturationMaturation and Fertilization
To investigate differences in immature oocyte maturation, fertilization, and pregnancy rates among women with unstimulated normal ovaries, polycystic ovaries (PCOs), or PCOS. Prospective observational study. 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.
Perimenopause/MenopauseSTRAW Staging SystemDefinition and StagingStaging Criteria
To determine whether the surgical diagnosis of endometriosis can be predicted using symptoms, signs, and ultrasound findings. Prospective study (study sample); retrospective record review (test sample). 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). 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.
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). . .
Contraception/ComparisonBone Health EffectsPremenopausal WomenRisk Factors
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. 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. 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. 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.
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.
Bone HealthQuality of Life ImpactFracture OutcomesPopulation-Based Studies
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 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.
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 ). 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.
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.
To evaluate the effect of supernumerary preovulatory follicular reduction as an approach to avoid multiple pregnancies in ovulation induction or superovulation cycles. Retrospective study. 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.
To evaluate the efficacy of progesterone and progestogens in the management of premenstrual syndrome. Systematic review of published randomised, placebo controlled trials. 10 trials of progesterone therapy (531 women) and four trials of progestogen therapy (378 women). 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. 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. The evidence from these meta-analyses does not support the use of progesterone or progestogens in the management of premenstrual syndrome.
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.
To test the efficacy of a community based 10 week exercise intervention to reduce fall risk factors in women with osteoporosis. 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. 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. 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.
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 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.
Although shortened cervical length has been consistently associated with spontaneous preterm birth, it is not known when in gestation this risk factor becomes apparent. 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, 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. 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. Spontaneous preterm birth before 35 weeks' gestation, analyzed by selected cutoff values of cervical length. 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). 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.
PostpartumPsychotropic Medication in LactationTreatment During BreastfeedingMedication Safety
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?
PCOSOvarian Androgen ProductionMetformin Mechanism of ActionThecal Cell Function
To examine the direct effect of metformin on thecal cell androgen production. 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.
PCOSCardiovascular RiskInsulin Resistance and Cardiac FunctionDiastolic Dysfunction in PCOS
To assess cardiac flow parameters in patients with polycystic ovary syndrome (PCOS). A prospective case-control study. 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.
PregnancyPublic Health EpidemiologyPerinatal Outcomes
Mattison DR et al., 2001·Paediatr Perinat Epidemiol
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.
PregnancyNurse Home Visit InterventionPrevention StrategiesPrenatal Care Models
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. Randomized clinical trial. 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. 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]. This model of care provides a reasoned solution to improving pregnancy and infant outcomes while reducing healthcare costs.
Fertility AwarenessBiomarker ComparisonUltrasound and Hormonal IndicesCervical Mucus and Urinary Hormones
To improve prediction of ovulation in normal cycles. Collection of women's characteristics and their menstrual cycles. Monitoring and analysis of time relationships between several transvaginal ultrasonography, cervical mucus, basal body temperature, urinary luteinising hormone, and ratio of urinary oestrogen to progesterone metabolites. Each of eight natural family planning clinics was to study 12 women for at least three cycles. One hundred and seven normally fertile and cycling women aged 18 to 45. 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. 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. 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. 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.
PCOSOvulation Induction and FertilityNeuroendocrine and Opioid DysfunctionHormone Therapy and Pharmacotherapy
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.
Perimenopause/MenopauseCardiovascular EffectsNatural Progesterone vs Synthetic ProgestinsRoute of Administration Effects
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 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 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 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 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.
PregnancyNeonatal Outcomes at Extreme PrematurityNICU Resource UtilizationExtremely Preterm Infant Survival
The objective of this study was to examine survival, morbidity, and resource use in a large cohort of extremely preterm infants. 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. 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. Extremely preterm infants have a high incidence of mortality and morbidity and consume disproportionate amounts of neonatal intensive care unit resources.
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.
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).
Prospective cohort study.
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.
To compare the effectiveness of i.m. P and 17alpha-hydroxyprogesterone caproate (17-HPC) for luteal phase support, in patients undergoing IVF-ET cycles. Prospective, randomized study. 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.