Recombinant human relaxin versus placebo for cervical ripening: a double-blind randomised trial in pregnant women scheduled for induction of labour.

BACKGROUND: Nonclinical studies indicate that the hormone relaxin is a good candidate for a safe cervical ripening agent that does not cause uterine contractions. METHODS: This Phase II study (conducted November 2, 2005-October 20, 2006) was a randomised, double blind, placebo controlled trial testing 24-h intravenous infusion of serelaxin (recombinant human relaxin) or placebo for cervical ripening in 72 healthy, primiparous women. Eligible subjects had a singleton pregnancy ≥40 weeks, were planned for elective induction, had vertex presentation of the fetus, intact membranes and a Bishop score at screening ≤4. In Part A of the study, safety evaluation of three escalating doses of serelaxin (7.5, 25 or 75 µg/kg/day) or placebo was performed in 22 subjects admitted to the hospital 24 h prior to scheduled induction (n = 7, 4, 4, and 7 subjects, respectively). The highest safe dose from Part A and placebo were then tested in Part B for safety and cervical ripening (n = 25 subjects/arm). Planned randomisation ratio was of 4:2 (serelaxin:placebo) for each dose group in Part A and 1:1 for Part B. For analysis, subjects in Part B were pooled with those receiving the same dose in Part A and all subjects receiving placebo were pooled. The primary efficacy endpoint was change from baseline in Bishop score at 6, 12 and 24 h or end of study drug administration. Maternal safety evaluations included adverse events and vital signs through 4 weeks. Fetal assessments included serial heart rate monitoring and nonstress testing. Neonatal assessments included Apgar scores, NICU admissions, and adverse events through 4 weeks. RESULTS: Overall, 74 subjects were randomized and 72 were treated. There were no significant differences between the groups receiving the highest safe dose of serelaxin (75 µg/kg/day) and placebo in the primary or secondary efficacy endpoints. Changes from baseline in Bishop score at 24 h were 4.19 ± 1.9 and 3.26 ± 2.26 in the pooled placebo and serelaxin groups, respectively (p = 0.2507). Serelaxin was well tolerated and no anti-serelaxin antibodies were detected in either subjects or neonates. CONCLUSION: Serelaxin infusion at the end of pregnancy was well tolerated but did not advance cervical ripening. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00259103 (15 November 2005).

Physical fitness, serum relaxin and duration of gestation.

BACKGROUND: Women are recommended to perform regular exercise during pregnancy but the impact of physical fitness on duration of gestation and miscarriage is inconsistent. In addition, a dose-response relation between the amount of weekly exercise and increased risk of miscarriage in early pregnancy has been observed. Previous studies have mostly used an epidemiologic method. Larger studies using careful measurement of physical fitness are needed. Besides physical fitness, maternal circulating concentrations of the hormone relaxin have been associated with decreased duration of gestation. METHODS: A prospective cohort including 20 women with miscarriage and 460 women with spontaneous onset of labour, recruited from maternal health care centres in central Sweden, were examined in early pregnancy regarding estimated absolute peak oxygen uptake (VO2 peak, est.) by cycle ergometer test, and maternal circulating serum relaxin concentrations. RESULTS: Women with miscarriage displayed the highest level of absolute VO2 peak, est. (2.61 l/min) and the lowest serum relaxin concentrations (640 ng/l). Among women with spontaneous onset of labour, the mean absolute VO2 peak, est. increased successively from the lowest estimated oxygen uptake of 2.31 l/min among those with preterm birth (n = 28), to an oxygen uptake of 2.49 l/min among women with postterm birth (n = 31). An opposite trend was shown regarding serum relaxin concentrations from women with miscarriage to those with postterm birth. Serum relaxin concentrations, but not absolute VO2 peak, est. was significantly and independently associated with duration of gestation in women with miscarriages, and absolute VO2 peak, est., age and multiple pregnancy were independently associated with duration of gestation in women with spontaneous onset of labour. CONCLUSIONS: Physical fitness appears to be a protective factor of established pregnancies and not significantly involved in the risk of early miscarriage. Additional studies are needed to more clearly define the role of relaxin in miscarriage.

Effect of single embryo transfer on the risk of preterm birth associated with in vitro fertilization.

PURPOSE: To determine whether elective single embryo transfer (eSET) reduces the risk of preterm delivery associated with in vitro fertilization (IVF). METHODS: This is an observational study of 3125 eSET cycles performed from 2008 to 2009 and reported to the Society for Assisted Reproductive Technology (SART) database. Preterm delivery rates were compared to the overall preterm delivery rate among all patients undergoing IVF over the same time period. RESULTS: The 3125 eSET cycles resulted in 1507 live births (live birth rate 48.2 %) Among these deliveries were 27 twins (1.8 %) and one set of triplets (0.07 %). The overall preterm delivery rate (20-37 weeks gestation) following eSET was 17.6 % (269/1527). This is significantly greater than the preterm birth rate for all patients undergoing IVF over the same time period (12 %, P < 0.001). CONCLUSIONS: Elective single embryo transfer does not reduce the risk of preterm delivery associated with in vitro fertilization (IVF).

Cardiovascular risk factor variation within a Hispanic cohort: SWAN, the Study of Women's Health Across the Nation.

OBJECTIVES: Hispanics have less favorable cardiovascular risk profiles relative to other groups, although little is known regarding variability in risk profiles according to country of origin. Our goal was to examine the association of cardiovascular risk factors with country of origin and acculturation in a cohort of middle-aged Hispanic women. SETTING: Baseline data for participants at the New Jersey Site of the Study of Women's Health Across the Nation (SWAN). PARTICIPANTS: 419 women, aged 42-52 years, comprising 142 non-Hispanic Whites and 277 Hispanic: Central American (n = 29), South American (n = 106), Puerto Rican (n = 56), Dominican (n = 42) and Cuban (n = 44). MAIN OUTCOME MEASURES: BMI, smoking, blood pressure, lipid profiles, and presence of hypertension, hyperlipidemia, diabetes and metabolic syndrome were compared using univariate and multivariable models. RESULTS: LDL and HDL varied significantly across Hispanic subgroups (overall P < or = .05). Prevalence of metabolic syndrome was greatest in Puerto Rican women (48.2% vs 40.0%, 35.0%, 13.9% and 29.3% in Central American, South American, Dominican and Cuban women, respectively, P = .016). Central American women were least likely to smoke (P < .05 vs Puerto Rican, Cuban and South American). Prevalence of hypertension and diabetes were similar across groups. Differences in lipids and metabolic syndrome were not explained by acculturation, financial strain, education, physical activity, smoking or dietary fat intake. CONCLUSIONS: There is significant heterogeneity in cardiovascular risk status among middle-aged Puerto Rican, Cuban, Dominican, Central American and South American women, not explained by acculturation or socioeconomic indicators. These differences may be important for targeting screening and preventive interventions.

Circulating relaxin and cervical length in midpregnancy are independently associated with spontaneous preterm birth.

OBJECTIVE: We sought to examine associations among serum relaxin levels, cervical length, and spontaneous preterm birth (sPTB). STUDY DESIGN: We conducted a case-control study within a cohort of 1080 singleton pregnant women. In all, 38 women (3.5%) delivered spontaneously preterm (< 37 completed weeks of gestation). Relaxin was measured in serum in gestational weeks 12 and 19, cervical length only in week 19. Associations to sPTB were evaluated by logistic regression analysis and receiver operating characteristic curves. RESULTS: Cervical length and relaxin in week 19, but not week 12 were associated to sPTB. There were no correlations between cervical length and relaxin level in week 12 (controls: Spearman rho: -0.07, P = .45; cases: Spearman rho: -0.07, P = .72) or week 19 (controls: Spearman rho: -0.03, P = .77; cases: Spearman rho: 0.04, P = .84). CONCLUSION: There were no correlation between relaxin concentrations and the cervical length, indicating that relaxin is probably not the cause of preterm shortening of the cervix.

Racial differences in women who have a hysterectomy for benign conditions.

OBJECTIVE: To evaluate if there are racial differences between African-American and Caucasian women who have hysterectomy for benign conditions in terms of (1) presenting symptoms (prolapse, vaginal bleeding, pain, and known history of leiomyomas), (2) serum estradiol and testosterone levels at the visit before hysterectomy, and (3) uterine weight. METHODS: A multi-ethnic, multisite, community-based longitudinal cohort study of 3,302 women ages 42-52 at enrollment was conducted. During 9 years of follow-up, 203 African-American and Caucasian women reported a hysterectomy, 90 with evidence of uterine leiomyomas. Women were surveyed regarding their overall perceived health before and after hysterectomy, presenting symptoms, and their motivations for surgery. Serum estradiol and testosterone levels were measured. Uterine weight at time of hysterectomy and clinical pathology were determined via medical record abstraction. RESULTS: Previously diagnosed leiomyomas were presenting symptoms more frequently in African-American women than Caucasian women (85% vs. 63%; p = .02). African-American women had less prolapse than Caucasian women (0% vs. 10%; p = 0.04). Chronic pain was a more frequent reason for hysterectomy in African-American women than in Caucasian women (49% vs. 29%; p = .05). There were no differences between the groups in levels of estradiol or testosterone. African-American women had almost twice the uterine weight as that of Caucasian women (448 vs. 240 g; p = .0005). CONCLUSION: Racial differences in frequency of hysterectomy for benign conditions are consistent with differences in presenting symptoms, where African-American women seemingly have larger, more symptomatic fibroids.

Menstrual Cycle Hormone Changes in Women Traversing Menopause: Study of Women's Health Across the Nation.

Context: Menstrual cycle hormone patterns in women approaching menopause are inadequately studied. Objective: To describe day-to-day menstrual cycle hormones in women as they approach menopause from the Study of Women's Health Across the Nation Daily Hormone Study (DHS). Design: DHS enrollees collected daily urine for one entire menstrual cycle or up to 50 days, whichever came first, annually, up to the final menstrual period (FMP) or for up to 10 years. Setting: Seven sites across the United States. Participants: A total of 511 premenopausal or early perimenopausal women at enrollment, within 10 years before menopause. Intervention: Time-to-FMP measurement. Main Outcome Measures: Evidence of luteal activity (ELA), determined using objective algorithms. Menstrual cycle/segment length; whole cycle, and segment integrated urinary luteinizing hormone, follicle-stimulating hormone, estrone conjugates, and pregnanediol glucuronide (Pdg) for each year, organized around the FMP. Results: Mean menstrual cycle length was remarkably preserved at 26 to 27 days in ELA cycles; non-ELA cycles had greater variability. The percentage of cycles that were ELA remained high until 5 years before the FMP (87.9%); only 22.8% of cycles within 1 year of the FMP were ELA. Whole cycle hormones remained relatively stable up to 3 years before the FMP, when gonadotropins began to increase. Pdg excretion declined slowly with progress to the FMP, but Pdg patterns of ELA cycles remained distinguishable from non-ELA. Conclusions: Menstrual cycle hormone patterns in perimenopausal women resemble those of midreproductive-aged women until 5 years before menopause, and presumably ovulatory cycles retain a potentially fertile pattern up to the end of reproductive life.

Role of Medical Management for Uterine Leiomyomas.

Uterine leiomyomas, or fibroids, are the most common benign tumor in reproductive aged women. Affected women may remain asymptomatic or may report symptoms related to abnormal uterine bleeding, infertility, or pelvic pain and pressure. Depending on a patient's symptomatology and reproductive plans, treatment options include expectant management, medical management (hormonal and non-hormonal), or surgical management (myomectomy or hysterectomy). In those wishing to defer surgical management, non-hormonal therapies such as non-steroidal anti-inflammatory drugs and tranexamic acid have been shown to decrease menstrual blood loss. In patients with more symptomatic leiomyomas, hormonal therapies such as gonadotropin-releasing hormone agonists and selective progesterone receptor modulators are effective at reducing leiomyoma volume, uterine size, and menstrual blood loss. This manuscript will detail the available and emerging hormonal and non-hormonal treatments for symptomatic uterine leiomyomas.

Correlates of circulating androgens in mid-life women: the study of women's health across the nation.

CONTEXT: Androgens influence sexual differentiation and behavior, body composition, and physical functioning in men, but their role in women is less well understood. Because circulating androgens decline with age, the use of androgen supplementation for women to improve health and well-being has been increasing. OBJECTIVE: The aim of this study was to assess the association between androgens and a variety of end points thought to be affected by androgens. DESIGN: In a community-based baseline cohort of women aged 42-52 yr from the Study of Women's Health Across the Nation, we measured circulating testosterone (T), dehydroepiandrosterone sulfate, and SHBG, and calculated a free androgen index (FAI) in 2961 women. MAIN OUTCOME MEASURES: Correlations of androgen measures with each other and with body mass index, waist circumference, and waist-hip ratio were computed, and odds ratios (OR) were estimated for the categorical outcomes of functional limitations, functional status, self-reported health, scores indicative of depressed mood, quality of life, sexual desire and arousal, and the presence of the metabolic syndrome. RESULTS: Androgens, and particularly SHBG, were associated most strongly with body mass index, waist circumference, and waist-hip ratio. SHBG was associated prominently inversely with the metabolic syndrome (OR = 0.32; 95% confidence interval = 0.26-0.39), which was present in 17% of women at baseline. Dehydroepiandrosterone sulfate was associated modestly with functional status and self-reported health. T was associated minimally with increased sexual desire (OR = 1.09; 95% confidence interval = 1.00-1.18). The association of FAI with self-reported health and depressive symptomatology based on the Center for Epidemiologic Studies Depression Scale score was explained more by T than by SHBG, whereas the association of FAI with sexual arousal and metabolic syndrome was due more to SHBG than to T. CONCLUSIONS: Circulating SHBG and androgens are most strongly associated with physical characteristics and the metabolic syndrome in women in this community-based cohort. Androgens are related weakly to physical functioning and other symptoms to which they commonly are attributed, such as sexual desire, sexual arousal, and well-being.

Relaxin regulates endometrial structure and function in the rhesus monkey.

The actions of relaxin are highly species specific. The role of relaxin in human endometrial function has not been well understood because of the paucity of in vivo studies in women or in suitable primate models. A model of early human pregnancy was established in ovariectomized, steroid-primed rhesus monkeys. Relaxin exerts dramatic uterine effects in this model, including a pronounced increase in uterine weight and stimulation of endometrial angiogenesis. In addition, relaxin negatively regulates expression of endometrial matrix metalloproteinases (MMP), causing decreased endometrial levels of MMP-1 and MMP-3 proteins and increased protein levels of their endogenous inhibitor, tissue inhibitor of metalloproteinase 1. This results in maintenance of endometrial collagen content. The negative effects of relaxin on MMP expression in the endometrium are in distinct contrast to the positive regulation of MMPs previously shown in fibroblasts from other tissues including the cervix. Relaxin also significantly inhibits endometrial levels of estrogen receptor alpha and significantly inhibits levels of progesterone isoforms B and A. The findings that relaxin stimulates new blood vessel formation while maintaining endometrial connective tissue integrity are consistent with a significant role of relaxin in the establishment and/or maintenance of early pregnancy.

Mechanisms of relaxin-mediated premature birth.

In women, circulating relaxin is produced by the corpus luteum of pregnancy. The levels of relaxin are predominantly determined by the luteal mass, the number of corpora lutea present. Relaxin levels are highest after ovulation induction, which stimulates formation of many corpora lutea. Elevated relaxin levels in the first trimester of pregnancy are maintained throughout pregnancy and are linearly related to preterm birth. In an in vitro model of late human pregnancy cervix, relaxin increases MMP-1 and MMP-3 and decreases TIMP-1 levels, thus acting as a positive regulator of matrix metalloproteinases. In an in vivo rhesus monkey model of early pregnancy, relaxin decreases cervical collagen content, decreases cervical lumican levels, and stimulates MMP-7 levels. Early effects of relaxin in the uterus include increasing endometrial arteriole number and increasing the number of leukocytes, uterine natural killer cells, macrophages, and neutrophils. These cells release many cytokines which contribute to changes that stimulate and facilitate uterine contractility. If these changes persist in late pregnancy, relaxin may be a mediator of labor. Excess relaxin may produce these changes at an accelerated rate, causing preterm birth.

Ethnic differences in past hysterectomy for benign conditions.

BACKGROUND: Hysterectomy for a benign condition is common, particularly in the underserved. The objective was to determine if ethnic differences could be explained by known risk factors. METHODS: A phone survey was conducted at random on 15,160 women, ages 40-55, from seven US cities. Subjects were 49.9% Caucasian, 28.1% African American, 12.3% Hispanic, and 9.8% Asian American. RESULTS: Ethnicity was associated with past hysterectomy (odds ratio [OR]: Caucasian = 1.0, African American = 1.66; confidence interval [CI] = 1.46-1.88, Hispanic = 1.64, CI = 1.29-2.07; Asian American = 0.44, CI = 0.34-0.56), after adjustment for age, education, fibroids, body mass index, marital status, smoking, geographic site, and country of education. CONCLUSION: Because the highest rates occurred in the disadvantaged African American and Hispanic subgroups, and could not be explained by known risk factors, disparity in the form of overuse in these disadvantaged groups may exist.

Ethnic differences in insulin sensitivity and beta-cell function in premenopausal or early perimenopausal women without diabetes: the Study of Women's Health Across the Nation (SWAN).

OBJECTIVE: To assess differences in insulin sensitivity and beta-cell function between nondiabetic premenopausal or early perimenopausal non-Hispanic white women and African American, Chinese American, Japanese American, and non-Mexican-American Latino women. RESEARCH DESIGN AND METHODS: Homeostasis model assessments (HOMAs) of insulin sensitivity (HOMA%S) and beta-cell function (HOMA%beta) were used. Stepwise multivariable ethnic-specific ANCOVA models were used to compare HOMA%S and HOMA%beta between non-Hispanic whites and each of the four ethnic groups. RESULTS: HOMA%S was lower in African Americans, Chinese Americans, and Japanese Americans when compared with non-Hispanic white women after correcting for waist circumference, presence of impaired fasting glucose, and site. Significant differences persisted only between African Americans and non-Hispanic whites after inclusion of triglycerides in the model. Triglycerides indirectly corrected for the differences in HOMA%S in the other two groups. There were no differences in HOMA%S between the non-Mexican-American Latinos and the non-Hispanic whites. Japanese Americans and Chinese Americans had lower HOMA%beta than non-Hispanic whites, whereas African Americans had higher HOMA%beta than non-Hispanic whites after correcting for confounders. HOMA%beta was similar between non-Mexican-American Latinos and non-Hispanic whites. CONCLUSIONS: These data suggest that type 2 diabetes prevention strategies for African-American women should initially target decreased insulin sensitivity, whereas strategies for Japanese-American and Chinese-American women may initially need to target both decreased insulin sensitivity and beta-cell function. Previous studies of Mexican-American populations may not apply to non-Mexican-American Latino women.

Does a diagnosis of atrophic vaginitis on Papanicolaou test signify the presence of inflammation?

OBJECTIVE: Vaginal atrophy in menopause shows increased parabasal cells on cytology. This may be accompanied by abundant neutrophils. A shift in maturation index in the absence of significant inflammation is more accurately termed "atrophic pattern." This study aims to determine whether a diagnosis of "atrophic vaginitis" or atrophic pattern on Papanicolaou test is a reliable indicator of what is present on the slide. METHODS: A retrospective review of Papanicolaou test slides from University Hospital Newark was performed. Cases that had been diagnosed as either atrophic vaginitis (n = 100) or atrophic pattern (n = 100) were selected. Exclusion criteria included any additional diagnosis of neoplasia. Slides were re-reviewed and scored based on abundance of neutrophils: 0 to 5, 6 to 10, or more than 10 neutrophils per high-power field (×40), with 10 fields per slide reviewed. Data were analyzed by χ analysis. RESULTS: Among 200 cases with atrophic vaginitis or atrophic pattern, the proportion of those diagnosed with atrophic vaginitis to those diagnosed with atrophic pattern increased across three neutrophil categories (P < 0.0001). CONCLUSIONS: A diagnosis of atrophic vaginitis on Papanicolaou test is reliably associated with increased numbers of neutrophils. A diagnosis of atrophic pattern is indicative of low numbers of neutrophils. As the Papanicolaou test diagnosis of atrophic vaginitis does not correlate with clinical symptoms, a single diagnostic term that does not suggest a disease process would more reliably communicate cytology findings to clinicians.

Myometrial artery calcifications and aging.

OBJECTIVE: This study aims to determine whether myometrial artery calcifications increase with age and whether uterine sections are an appropriate model for studying vascular aging. METHODS: An observational study of 172 women (aged 45 y or older) who underwent hysterectomy for benign indications at the University Hospital (Newark, NJ) between July 1, 2009 and June 1, 2012 was performed. Women with a history of malignancy, undocumented last menstrual period, or unavailable uterine tissue slides were excluded. H&E-stained uterine sections were evaluated for myometrial artery calcifications (defined as the presence of acellular densely basophilic material within the media of vessels) by a single pathologist in a blinded manner. RESULTS: Between July 1, 2009 and June 1, 2012, hysterectomies were performed on 441 women, 172 of whom met inclusion criteria. Seventeen women (9.9%) had myometrial artery calcifications detectable on H&E-stained tissue sections. None of 84 women aged 45 to 49 years, 2 of 51 women (3.9%) aged 50 to 59 years (aged 56 and 58 y), 10 of 27 women (37%) aged 60 to 69 years, and 5 of 10 women (50%) aged 70 to 81 years had myometrial artery calcifications. The prevalence of myometrial artery calcifications significantly increased with advancing age (P = 0.022). CONCLUSIONS: Myometrial artery calcifications increase with advancing age. Histological sections of uterine tissue from hysterectomy specimens seem to be a useful model for evaluating vascular aging markers.

The relationship of circulating dehydroepiandrosterone, testosterone, and estradiol to stages of the menopausal transition and ethnicity.

In this report, 3029 women between the ages of 42 and 54 yr from five ethnic groups were studied for 2 yr. Log circulating dehydroepiandrosterone sulfate (DHEAS) concentrations were highest among Chinese and Japanese and lowest among African Americans and Hispanics, and this pattern persisted after adjustment for age, smoking, and log body mass index (BMI). With the exception of Japanese women, log BMI was negatively related to log circulating DHEAS. The magnitude of this association varied by ethnic group, and the decline in log circulating DHEAS levels with higher log BMI was steepest for Chinese and least steep for Hispanics. The relationship between log DHEAS and log BMI was positive for Japanese. DHEAS levels did not decline at a steady rate during the menopausal transition and transiently increased in some women and increased, on average, during the transition to late perimenopause. These increases tended to be larger for Chinese, Hispanic, and Japanese than for African Americans and Caucasians, although the interactions were not statistically significant. Changes in circulating testosterone and, to a lesser extent, estradiol were correlated to changes in DHEAS. These data have importance in understanding the endocrinology of the menopausal transition, defining the relationship of adrenal steroid production during declining ovarian function and determining a rationale regarding DHEAS supplementation for older women.

Body size and ethnicity are associated with menstrual cycle alterations in women in the early menopausal transition: The Study of Women's Health across the Nation (SWAN) Daily Hormone Study.

The dynamics of reproductive hormones that characterize the menopausal transition (perimenopause) are incompletely understood, particularly in non-Caucasian women. The Study of Women's Health across the Nation (SWAN) is a multiethnic cohort study of 3302 women at seven sites who were aged 42-52 yr at baseline. All participants are seen annually to assess a variety of endpoints. A subcohort of 848 women undergoes further investigation of their daily patterns of reproductive hormones in the Daily Hormone Study (DHS). DHS enrollees annually complete a daily collection of first morning voided urine for an entire menstrual cycle or up to 50 d (whichever comes first). Chemiluminescent assays measured urinary LH and FSH, as well as metabolites of estradiol [estrone conjugates (E1c)] and progesterone [pregnanediol glucuronide (Pdg)]. Cycles were assessed for evidence of luteal activity and day of luteal transition using previously developed algorithms. Midreproductive-aged women who underwent similar daily urinary analyses served as historical controls. Correlates of cycle features were identified. Eight hundred thirty-three cycles were evaluable and had complete data on covariates. Six hundred seventy-four (80.9%) cycles had evidence of luteal activity, and 159 (19.1%) did not. Women who were at least 49 yr old were less likely to have cycles with luteal activity and had more variable cycle length, higher total-cycle FSH, and lower total-cycle Pdg. Compared with heavier women, those with body mass index less than 25 kg/m2 had shorter cycles and higher total-cycle LH, FSH, and Pdg but not E1c. Chinese- and Japanese-American women had overall lower adjusted total-cycle E1c excretion. Smoking was not significantly associated with cycle length or hormones. When compared with cycles of younger control women, the cycles of the SWAN DHS participants had higher gonadotropins, lower total integrated Pdg, and E1c levels that were not different, which suggests that the ovary retains sensitivity to elevated FSH in the early menopausal transition. In this cross-sectional study of women over age 42 who are premenopausal or in the early menopausal transition, there were important differences in the characteristics of cycles related to age, body mass index, and ethnicity. Comparisons to younger women indirectly support the inhibin hypothesis, which proposes that the initiating event in the menopausal transition is the loss of inhibin negative feedback on FSH secondary to a diminished follicular reserve.

So what is the role of menstrual bacterial endotoxin?

Bacterial infections may adversely affect ART. However, the meaning and risks of menstrual endotoxin are not known.

Increased risk of preterm birth in singleton pregnancies resulting from in vitro fertilization-embryo transfer or gamete intrafallopian transfer: a meta-analysis.

OBJECTIVE: To perform a systematic review of the literature to determine whether singleton pregnancies resulting from IVF-ET/GIFT are at higher risk for preterm birth (<37 weeks). DESIGN: Literature search and systematic review. SETTING: Medical school. INTERVENTION(S): A MEDLINE search (1965-2000) was performed using the terms "premature labor," "infertility," "pregnancy complications," "gonadotropins," "pregnancy outcome," "preterm delivery," and "in vitro fertilization." Criteria for inclusion were English language, original research article, study patients conceived using IVF-ET (with or without intracytoplasmic sperm injection) or GIFT, pregnancy outcome reported compared with a control group (e.g., naturally conceived singletons at their hospital or a national reference), and prematurity clearly defined. Incomplete articles (e.g., abstracts), reports of other studies, and studies that failed to separate multiple from singleton gestations were excluded. MAIN OUTCOME MEASURE(S): Summary of relative risks of preterm birth. RESULT(S): Twenty-seven articles met all inclusion/exclusion criteria and were analyzed by meta-analysis. The random-effects summary relative risk of preterm birth in singleton pregnancies resulting from IVF-ET/GIFT was 1.98 (95% confidence interval, 1.77-2.22). CONCLUSION(S): The risk of preterm birth in singleton pregnancies resulting from IVF-ET/GIFT is twice that of natural conceived pregnancies.