Effects of acupuncture on rates of pregnancy and live birth among women undergoing in vitro fertilisation: systematic review and meta-analysis

Objective To evaluate whether acupuncture improves rates of pregnancy and live birth when used as an adjuvant treatment to embryo transfer in women undergoing in vitro fertilisation.Design Systematic review and meta-analysis.Data sources Medline, Cochrane Central, Embase, Chinese Biomedical Database, hand searched abstracts, and reference lists.Review methods Eligible studies were randomised controlled trials that compared needle acupuncture administered within one day of embryo transfer with sham acupuncture or no adjuvant treatment, with reported outcomes of at least one of clinical pregnancy, ongoing pregnancy, or live birth. Two reviewers independently agreed on eligibility; assessed methodological quality; and extracted outcome data. For all trials, investigators contributed additional data not included in the original publication (such as live births). Meta-analyses included all randomised patients.Data synthesis Seven trials with 1366 women undergoing in vitro fertilisation were included in the meta-analyses. There was little clinical heterogeneity. Trials with sham acupuncture and no adjuvant treatment as controls were pooled for the primary analysis. Complementing the embryo transfer process with acupuncture was associated with significant and clinically relevant improvements in clinical pregnancy (odds ratio 1.65, 95% confidence interval 1.27 to 2.14; number needed to treat (NNT) 10 (7 to 17); seven trials), ongoing pregnancy (1.87, 1.40 to 2.49; NNT 9 (6 to 15); five trials), and live birth (1.91, 1.39 to 2.64; NNT 9 (6 to 17); four trials). Because we were unable to obtain outcome data on live births for three of the included trials, the pooled odds ratio for clinical pregnancy more accurately represents the true combined effect from these trials rather than the odds ratio for live birth. The results were robust to sensitivity analyses on study validity variables. A prespecified subgroup analysis restricted to the three trials with the higher rates of clinical pregnancy in the control group, however, suggested a smaller non-significant benefit of acupuncture (odds ratio 1.24, 0.86 to 1.77).Conclusions Current preliminary evidence suggests that acupuncture given with embryo transfer improves rates of pregnancy and live birth among women undergoing in vitro fertilisation.     

Expectations of assisted conception for infertility.

OBJECTIVE--To provide reliable prognostic information for couples seeking assisted conception. DESIGN--Analysis of four years'' practice (1988-91). SETTING--Private university service linked with NHS reproductive medicine services. PATIENTS--804 couples with various causes of subfertility, median duration five years, median age of women 34 years. INTERVENTIONS--1280 completed cycles: 950 in vitro fertilisation, 144 gamete intrafallopian transfer, and 186 intrauterine insemination and superovulation. MAIN OUTCOME MEASURES--Pregnancy and birth rates per cycle and cumulative pregnancy and take home baby rates per couple. RESULTS--In women under 40 years and men with normal sperm, whatever the cause of infertility, results with in vitro fertilisation improved steadily reaching a pregnancy rate per cycle of 30% (95% confidence interval 26% to 35%) during 1990-1 and birth rate per cycle of 29% (23% to 35%) in 1990. Pregnancy and birth rates for gamete intrafallopian transfer were 36% (28% to 44%) and 26% (17% to 37%) and for intrauterine insemination 18% (12% to 24%) and 16% (10% to 22%). After six cycles cumulative probability of pregnancy was 82% and cumulative take home baby rate 70%. Considering only in vitro fertilisation and gamete intrafallopian transfer after four cycles the pregnancy rate was 78% (66% to 91%). CONCLUSIONS--Conception is less likely in women over 40 and men with sperm dysfunction. For other couples the prognosis for a live birth is at least as good as for fertile couples if they persist with treatment.     

External Validation and Calibration of IVFpredict: A National Prospective Cohort Study of 130,960 In Vitro Fertilisation Cycles

Background

Accurately predicting the probability of a live birth after in vitro fertilisation (IVF) is important for patients, healthcare providers and policy makers. Two prediction models (Templeton and IVFpredict) have been previously developed from UK data and are widely used internationally. The more recent of these, IVFpredict, was shown to have greater predictive power in the development dataset. The aim of this study was external validation of the two models and comparison of their predictive ability.

Methods and Findings

130,960 IVF cycles undertaken in the UK in 2008–2010 were used to validate and compare the Templeton and IVFpredict models. Discriminatory power was calculated using the area under the receiver-operator curve and calibration assessed using a calibration plot and Hosmer-Lemeshow statistic. The scaled modified Brier score, with measures of reliability and resolution, were calculated to assess overall accuracy. Both models were compared after updating for current live birth rates to ensure that the average observed and predicted live birth rates were equal. The discriminative power of both methods was comparable: the area under the receiver-operator curve was 0.628 (95% confidence interval (CI): 0.625–0.631) for IVFpredict and 0.616 (95% CI: 0.613–0.620) for the Templeton model. IVFpredict had markedly better calibration and higher diagnostic accuracy, with calibration plot intercept of 0.040 (95% CI: 0.017–0.063) and slope of 0.932 (95% CI: 0.839–1.025) compared with 0.080 (95% CI: 0.044–0.117) and 1.419 (95% CI: 1.149–1.690) for the Templeton model. Both models underestimated the live birth rate, but this was particularly marked in the Templeton model. Updating the models to reflect improvements in live birth rates since the models were developed enhanced their performance, but IVFpredict remained superior.

Conclusion

External validation in a large population cohort confirms IVFpredict has superior discrimination and calibration for informing patients, clinicians and healthcare policy makers of the probability of live birth following IVF.     

Improving the Rank Precision of Population Health Measures for Small Areas with Longitudinal and Joint Outcome Models

Objectives

The University of Wisconsin Population Health Institute has published the County Health Rankings since 2010. These rankings use population-based data to highlight health outcomes and the multiple determinants of these outcomes and to encourage in-depth health assessment for all United States counties. A significant methodological limitation, however, is the uncertainty of rank estimates, particularly for small counties. To address this challenge, we explore the use of longitudinal and pooled outcome data in hierarchical Bayesian models to generate county ranks with greater precision.

Methods

In our models we used pooled outcome data for three measure groups: (1) Poor physical and poor mental health days; (2) percent of births with low birth weight and fair or poor health prevalence; and (3) age-specific mortality rates for nine age groups. We used the fixed and random effects components of these models to generate posterior samples of rates for each measure. We also used time-series data in longitudinal random effects models for age-specific mortality. Based on the posterior samples from these models, we estimate ranks and rank quartiles for each measure, as well as the probability of a county ranking in its assigned quartile. Rank quartile probabilities for univariate, joint outcome, and/or longitudinal models were compared to assess improvements in rank precision.

Results

The joint outcome model for poor physical and poor mental health days resulted in improved rank precision, as did the longitudinal model for age-specific mortality rates. Rank precision for low birth weight births and fair/poor health prevalence based on the univariate and joint outcome models were equivalent.

Conclusion

Incorporating longitudinal or pooled outcome data may improve rank certainty, depending on characteristics of the measures selected. For measures with different determinants, joint modeling neither improved nor degraded rank precision. This approach suggests a simple way to use existing information to improve the precision of small-area measures of population health.     

Dominance hierarchy and social relationships in a group of Captive black-and-white snub-nosed monkeys (Rhinopithecus bieti)

Different types of dominance hierarchies reflect different social relationships in primates. In this study, we clarified the hierarchy and social relationships in a one-male unit of captive Rhinopithecus bieti observed between August 1998 and March 1999. Mean frequency of agonistic behaviour among adult females was 0.13 interactions per hour. Adult females exhibited a linear hierarchy with a reversal of 10.9%, indicating an unstable relationship; therefore, R. bieti appears to be a relaxed/tolerant species. The lack of a relationship between the agonistic ratio of the adult male towards adult females and their ranks indicated that males did not show increased aggression towards low-ranking females. Differentiated female affiliative relationships were loosely formed in terms of the male, and to some extent influenced by female estrus, implying that relationships between the male and females is influenced by estrus and not rank alone. A positive correlation between the agonistic ratio of adult females and their ranks showed that the degree to which one female negatively impacted others decreased with reduction in rank. Similarly, a positive correlation between the agonistic ratio of females and differences in rank suggests that a female had fewer negative effects on closely ranked individuals than distantly ranked ones. These data indicate that rank may influence relationships between females. A steeper slope of regression between the agonistic ratio and inter-female rank differences indicated that the extent of the power difference in high-ranking females exerting negative effects on low-ranking ones was larger during the mating season than the birth season, suggesting that rank may influence the mating success of females.     

A Retrospective Study Examining Phentermine on Preconception Weight Loss and Pregnancy Outcomes

Objective: Obesity is a well-known risk factor for infertility. However, the use of weight loss medications prior to conception is underutilized. The objectives of our study are to describe weight loss, pregnancy rates, and live birth rates after short-term phentermine use in women with obesity and infertility.Methods: This was a retrospective analysis of 55 women (18 to 45 years old) who were overweight or obese, diagnosed with infertility, and prescribed phentermine for weight loss in an ambulatory endocrinology clinic at a single, tertiary level academic medical center. Main outcome measures were mean percent weight change at 3 months after starting phentermine, and pregnancy, and live birth rates from start of phentermine to June 30, 2017.Results: Median duration of phentermine use was 70 days (Q1, Q3 &lsqb;33, 129]). Mean ± SD percent weight change at 3 months after starting phentermine was -5.3 ± 4.1% (P<.001). The pregnancy rate was 60% and the live birth rate was 49%. There was no significant difference in pregnancy rates (52% versus 68%; P = .23) or live birth rates (44% versus 54%; P = .50) in women who lost ≥5% versus <5% of their baseline weight. The number of metabolic comorbidities was negatively associated with the pregnancy rate. Phentermine was generally well-tolerated with no serious adverse events.Conclusion: Phentermine can produce clinically significant weight loss in women with obesity during the preconception period. Higher pregnancy or live birth rates were not observed with a greater degree of weight loss with phentermine.     

The effects of dominance rank and group size on female lifetime reproductive success in wild long-tailed macaques,Macaca fascicularis

Demographic changes were recorded throughout a 12-year period for three social groups ofMacaca fascicularis in a natural population at Ketambe (Sumatra, Indonesia). We examined the prediction that females' lifetime reproductive success depended on dominance rank and group size. Average birth rate was 0.53 (184 infants born during 349 female years). For mature females (aged 8–20 yr) birth rate reflected physical condition, being higher in years with high food availability and lower in the year following the production of a surviving infant. High-ranking females were significantly more likely than low-ranking ones to give birth again when they did have a surviving offspring born the year before (0.50 vs 0.26), especially in years with relatively low food availability (0.37 vs 0.10). Controlled comparisons of groups at different sizes indicate a decline in birth rate with rroup size only once a group has exceeded a certain size. The dominance effect on birth rate tended to be strongest in large groups. Survival of infants was rank-dependent, but the survival of juveniles was not. There was a trend for offspring survival to be lower in large groups than in mid-sized or small groups. However, rank and group size interacted, in that rank effects on offspring survival were strongest in large groups. High-ranking females were less likely to die themselves during their top-reproductive years, and thus on average had longer reproductive careers. We estimated female lifetime reproductive success based on calculated age-specific birth rates and survival rates. The effects of rank and group size (contest and scramble) on birth rate, offspring survival, age of first reproduction for daughters, and length of reproductive career, while not each consistently statistically significant, added up to substantial effects on estimated lifetime reproductive success. The group size effects explain why large groups tend to split permanently. Since females are philopatric in this species, and daughters achieve dominance rank positions similar to their mother, a close correlation is suggested between the lifetime reproductive success of mothers and daughters. For sons, too, maternal dominance affected their reproductive success: high-born males were more likely to become top-dominant (in another group). These data support the idea that natural selection has favored the evolution of a nepotistic rank system in this species, even if the annual benefits of dominance are small.     

Live Birth and Cumulative Live Birth Rates in Expected Poor Ovarian Responders Defined by the Bologna Criteria Following IVF/ICSI Treatment

ObjectiveTo determine the live birth and cumulative live birth rates of expected poor ovarian responders according to the Bologna criteria and to compare their outcomes with those of expected normal respondersDesignRetrospective analysisSettingUniversity infertility clinicPatientsA total of 1,152 subfertile women undergoing their first in vitro fertilization (IVF) cycleInterventionsWomen were classified into 4 groups according to the Bologna criteria for comparisonResultsWomen with expected poor response (POR) had the lowest live birth rate than the other 3 groups (23.8%, p = 0.031). Cumulative live birth rates were significantly lower in those with expected POR than those with expected normal ovarian response (NOR) (35.8% vs 62.8%, p<0.0001). In the subgroup analysis, the cumulative live birth rates in expected PORs were significantly lower in those who had ≤3 oocytes retrieved (18.6% for ≤3 oocytes vs 44.0% for >3 oocytes, p = 0.006) whereas the live birth rates in fresh cycle did not differ (17.8% vs 30.9%, p = 0.108).ConclusionWomen who were expected POR according to the Bologna criteria had lower live birth and cumulative live birth than expected NOR but they still can achieve reasonable treatment outcomes and IVF treatment should not be precluded.     

Using registry data to suggest which birth defects may be more susceptible to artifactual clusters and trends

BACKGROUND: Some birth defects appear to be more susceptible than others to artifactual prevalence variability over time or geographically. This article uses an empirical approach to try to identify them. METHODS: Assumption: Variation in clinical practice and other artifactual sources of variability impact observed variation in prevalence of mild cases more than severe cases for a given birth defect. Approach: Data were examined from Texas Birth Defects Registry deliveries from 1999-2003. For each of 312 delivery hospitals, birth prevalence for mild cases was calculated for birth defect X. The 5(th) percentile was subtracted from the 95(th) percentile to measure spread in the frequency distribution of all hospitals. That was repeated for severe cases. The ratio of the mild:severe spread was calculated for 49 defects, and the defects ranked into quintiles. That was repeated using birth prevalence based on county, and using isolated cases. The percentages of severe cases were calculated and also ranked into quintiles. A sensitivity analysis and simulation were conducted. RESULTS: Forty-nine birth defects were ranked from those least susceptible to differences in mild:severe prevalence variability (e.g., anencephaly, hypoplastic left heart syndrome) to most susceptible (e.g., atrial septal defect, fetal alcohol syndrome). Resulting quintile ranks based on the three measures were highly correlated, whether based on all cases or isolated cases. CONCLUSIONS: This empirical approach may be helpful for a number of public health applications. Birth defects and other health outcomes more susceptible to prevalence variability may be more likely to exhibit artifactual trends or clusters.     

The generation of live offspring from vitrified oocytes

Oocyte cryopreservation is extremely beneficial for assisted reproductive technologies, the treatment of infertility and biotechnology and offers a viable alternative to embryo freezing and ovarian grafting approaches for the generation of embryonic stem cells and live offspring. It also offers the potential to store oocytes to rescue endangered species by somatic cell nuclear transfer and for the generation of embryonic stem cells to study development in these species. We vitrified mouse oocytes using a range of concentrations of trehalose (0 to 0.3 M) and demonstrated that 0.1 and 0.3 M trehalose had similar developmental rates, which were significantly different to the 0.2 M cohort (P<0.05). As mitochondria are important for fertilisation outcome, we observed that the clustering and distribution of mitochondria of the 0.2 M cohort were more affected by vitifrication than the other groups. Nevertheless, all 3 cohorts were able to develop to blastocyst, following in vitro fertilisation, although developmental rates were better for the 0.1 and 0.3 M cohorts than the 0.2 M cohort (P<0.05). Whilst blastocysts gave rise to embryonic stem-like cells, it was apparent from immunocytochemistry and RT-PCR that these cells did not demonstrate true pluripotency and exhibited abnormal karyotypes. However, they gave rise to teratomas following injection into SCID mice and differentiated into cells of each of the germinal layers following in vitro differentiation. The transfer of 2-cell embryos from the 0.1 and 0.3 M cohorts resulted in the birth of live offspring that had normal karyotypes (9/10). When 2-cell embryos from vitrified oocytes underwent vitrification, and were thawed and transferred, live offspring were obtained that exhibited normal karyotypes, with the exception of one offspring who was larger and died at 7 months. We conclude that these studies highlight the importance of the endometrial environment for the maintenance of genetic stability and thus the propagation of specific genetic traits.     

Role of Baseline Antral Follicle Count and Anti-Mullerian Hormone in Prediction of Cumulative Live Birth in the First In Vitro Fertilisation Cycle: A Retrospective Cohort Analysis

Objective

This retrospective study determined for the first time the role of baseline antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) level in the first in-vitro fertilisation (IVF) cycle in predicting cumulative live birth from one stimulation cycle.

Methods

We studied 1,156 women (median age 35 years) undergoing the first IVF cycle. Baseline AFC and AMH level on the day before ovarian stimulation were analysed. The main outcome measure was cumulative live birth in the fresh plus all the frozen embryo transfers after the same stimulation cycle.

Results

Serum AMH was significantly correlated with AFC. Both AMH and AFC showed significant correlation with age and ovarian response in the stimulated cycle and total number of transferrable embryos. Baseline AFC and serum AMH were significantly higher in subjects attaining a live birth than those who did not in the fresh stimulated cycle, as well as those attaining cumulative live birth. There was a significant trend of higher cumulative live birth rate in women with higher AMH or AFC. However, logistic regression revealed that both AMH and AFC were not significant predictors of cumulative live birth after adjusting for age and number of embryos available for transfer. Considering only one single predictor, the areas under the ROC curves for AMH (0.646, 95% CI 0.616–0.675) and age (0.648, 95% CI 0.618–0.677) were slightly higher than that for AFC (0.617, 95% CI 0.587–0.647) in predicting cumulative live birth. However, a model combining AMH (with or without AFC) and age of the women only classified an addition of less than 2% of subjects correctly compared to the model with age alone.

Conclusion

Baseline AFC and serum AMH have only modest predictive performance on the occurrence of cumulative live birth, and may not give additional value on top of the women''s age.     

Preimplantation Genetic Diagnosis and Natural Conception: A Comparison of Live Birth Rates in Patients with Recurrent Pregnancy Loss Associated with Translocation

Background

Established causes of recurrent pregnancy loss (RPL) include antiphospholipid syndrome, uterine anomalies, parental chromosomal abnormalities, particularly translocations, and abnormal embryonic karyotypes. The number of centers performing preimplantation genetic diagnosis (PGD) for patients with translocations has steadily increased worldwide. The live birth rate with PGD was reported to be 27-54%. The live birth rate with natural conception was reported to be 37-63% on the first trial and 65-83% cumulatively. To date, however, there has been no cohort study comparing age and the number of previous miscarriages in matched patients undergoing or not undergoing PGD. Thus, we compared the live birth rate of patients with RPL associated with a translocation undergoing PGD with that of patients who chose natural conception.

Methods and Findings

After genetic counseling, 52 patients who desired natural conception and 37 patients who chose PGD were matched for age and number of previous miscarriages and these comprised the subjects of our study. PGD was performed by means of fluorescence in situ hybridization analysis. The live birth rates on the first PGD trial and the first natural pregnancy after ascertainment of the carrier status were 37.8% and 53.8%, respectively (odds ratio 0.52, 95% confidence interval 0.22-1.23). Cumulative live birth rates were 67.6% and 65.4%, respectively, in the groups undergoing and not undergoing PGD. The time required to become pregnancy was similar in both groups. PGD was found to reduce the miscarriage rate significantly. The prevalence of twin pregnancies was significantly higher in the PGD group. The cost of PGD was $7,956 U.S. per patient.

Conclusions

While PGD significantly prevented further miscarriages, there was no difference in the live birth rate. Couples should be fully informed of the similarity in the live birth rate, the similarity in time to become pregnancy, the advantages of PGD, such as the reduction in the miscarriage rate, as well as its disadvantages, such as the higher cost, and the advantages of a natural pregnancy, such as the avoidance of IVF failure. The findings presented here should be incorporated into the genetic counseling of patients with RPL and carrying a translocation.     

In Vitro Maturation in Women with vs. without Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis

Objective

To evaluate in vitro maturation (IVM) in sub-fertile women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilisation (IVF), by comparing outcomes with a control group of non-PCOS.

Study design

A search strategy was developed for PubMed and studies reporting rates of the following outcomes (live birth; clinical pregnancy; implantation; cycle cancellation; oocyte maturation; oocyte fertilization; miscarriage) between patients with PCOS, PCO and controls undergoing IVM were deemed eligible. The review was conducted in accordance to the PRISMA guidelines and included studies quality was assessed through the Newcastle-Ottawa Quality scale. ORs with their corresponding 95% CIs were calculated for the main analysis and subgroup analyses were performed for PCOS cases vs. controls and PCOS vs. PCO cases. Alternative analyses were performed for live birth and clinical pregnancy, based on cycles and on women. Subgroup analyses for FSH stimulation, hCG priming and type of procedure (IVF/ICSI) were undertaken for all meta-analyses encompassing at least four study arms. Random effects models were used to calculate pooled effect estimates.

Results

Eleven studies were identified. A total of 268 PCOS patients (328 cycles), 100 PCO patients (110 cycles) and 440 controls (480 cycles) were included in the meta-analysis. A borderline trend towards higher birth rates among PCOS patients emerged (pooled OR = 1.74, 95%CI: 0.99–3.04) mainly reflected at the subgroup analysis vs. controls. Clinical pregnancy (pooled OR = 2.37, 95%CI: 1.53–3.68) and implantation rates (pooled OR = 1.73, 95%CI: 1.06–2.81) were higher, while cancellation rates lower (pooled OR = 0.18, 95%CI: 0.06-0.47) among PCOS vs. non-PCOS subjects; maturation and miscarriage rates did not differ between groups, while a borderline trend towards lower fertilization rates among PCOS patients was observed.

Conclusion

The present meta-analysis provides preliminary evidence on the effectiveness of IVM as a treatment option when offered in sub-fertile PCOS women, as the latter present at least as high outcome rates as those in non-PCOS.     

PocketDepth: a new depth based algorithm for identification of ligand binding sites in proteins

Predicting functional sites in proteins is important in structural biology for understanding the function and also for structure-based drug design. Here we report a new binding site prediction method PocketDepth, which is geometry based and uses a depth based clustering. Depth is an important parameter considered during protein structure visualisation and analysis but has been used more often intuitively than systematically. Our current implementation of depth reflects how central a given subspace is to a putative pocket. We have tested the algorithm against PDBbind, a large curated set of 1091 proteins. A prediction was considered a true-positive if the predicted pocket had at least 10% overlap with the actual ligand. Two different parameter sets, 'deeper' and 'surface' were used, for wider coverage of different types of binding sites in proteins. With deeper parameters, true-positives were observed for 841 proteins, resulting in a prediction accuracy of 77%, for any ranked prediction. Of these, 55.2% were first ranked predictions, whereas 91.2% and 97.4% were covered in the first 5 and 10 ranks, respectively. With the 'surface' parameters, a prediction rate of 95.8% was observed, albeit with much poorer ranks. The deeper set identified pocket boundaries more precisely and yielded better ranks, while the latter missed fewer predictions and hence had better coverage. The two parameter sets were therefore algorithmically combined, resulting in prediction accuracies of 96.5% for any ranked prediction. About 41.8% of these were in the first rank, 82% and 94% were in top 5 and 10 ranks, respectively. The algorithm is available at http://proline.physics.iisc.ernet.in/pocketdepth.     

Effects of prolonging administration gonadotropin on unexpectedly poor ovarian responders undergoing in vitro fertilization

Background

There are still some patients who show poor response to ovarian stimulation prior to evidence of normal ovarian reserve in vitro fertilization. However, there are few studies about how to treat the unexpectedly ovarian poor responder in vitro fertilization. The main aim of this study evaluate the effect of prolonging administration follicle-stimulating hormone in woman with the unexpectedly ovarian poor responder in vitro fertilization on implantation rate, clinical pregnancy rate and live birth rate.

Methods

922 patients subjected to IVF were divided into two groups according to the predicted criterion of ovarian poor response. 116 patients predicted poor response received the short protocol (group C). The others received the long protocol, among the latter, there were 149 patients undergoing unexpectedly ovarian poor response (group B) and 657 patients exhibited normal ovarian response (group A). The doses of gonadotropin, duration of administration, implantation rate, clinical pregnancy rate and live birth rate were recorded among three groups.

Results

The implantation rate of embryo, clinic pregnancy rate and delivery rate are similar between the group A and group B, while there are significant differences between the doses of gonadotropins (35.1 +/- 8.9 ampules vs.53.0 +/- 15.9 ampules) and the duration of administration (15.3 +/- 3.6D vs. 9.8 +/- 2.6D) of these two groups. There are no significant differences about clinical pregnancy rate and live birth rate between group B and group C.

Conclusion

Prolonging administration gonadotropin on the unexpectedly poor ovarian responders does not lower live birth rate in vitro fertilization.     

Variability and stability in the rank relations of nonhuman primate females: Analysis by computer simulation

This paper summarizes results of simulation analyses aimed at elucidating the way in which two important dimensions of female rank orders—nepotism and age-gradedness—are affected by variation in individual strategies of rank acquisition on the one hand and by variation in population-wide demographic parameters (eg, birth rate, death rate, etc) on the other. Female rank orders in simulated primate groups were characterized by substantial variability on a year-to-year basis in both nepotism and age-gradedness owing to stochastic processes alone. Although, in general, groups characterized by strongly nepotistic rank orders were not also strongly age-graded, quantitative measures of these two rank-order dimensions for individual groups showed little stability over intervals of time exceeding 3 years. Surprisingly, changes in birth and death rates did not strongly affect either nepotism or age-gradedness so long as average group size remained constant. However, in populations characterized by expanding or declining group size, variation in demographic parameters did indeed exert a powerful influence on the structure of female rank orders. Both nepotism and age-gradedness were also strongly affected, and in quite different ways, by changes in the rules of rank acquisition by females. In sum, the present analyses suggest that differences between species in the degree of nepotism and age-gradedness characteristic of their female rank orders does not in and of itself constitute evidence that the females of those species use markedly different strategies of rank acquisition.     

Perinatal mortality and adverse pregnancy outcomes in a low-income rural population of women who smoke

We describe adverse pregnancy outcomes, including congenital anomalies, fetal, neonatal, and infant mortality among a Missouri population of low-income, rural mothers who participated in two randomized smoking cessation trials. In the Baby BEEP (BB) trial, 695 rural women were recruited from 21 WIC clinics with 650 women's pregnancy outcomes known (93.5% retention rate). Following the BB trial, 298 women who had a live infant after November 2004 were recruited again into and completed the Baby Beep for Kids (BBK) trial. Simple statistics describing the population and perinatal and postneonatal mortality rates were calculated. Of the adverse pregnancy outcomes (n = 79), 29% were spontaneous abortions of less than 20 weeks' gestation, 23% were premature births, and 49% were identified birth defects. The perinatal mortality rate was 15.9 per 1000 births (BB study) compared with 8.6 per 1000 births (state of Missouri) and 8.5 per 1000 births (United States). The postneonatal infant mortality rate was 13.4 per 1000 live births (BBK) compared with 2.1 per 1000 live births (United States). The health disparity in this population of impoverished, rural, pregnant women who smoke, particularly in regard to perinatal and infant deaths, warrants attention.     

Anti-Müllerian hormone (AMH) is a strong predictor of live birth in women undergoing assisted reproductive technology

In the present study, we evaluated the clinical value of the following parameters: basal anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), inhibin B and antral follicle count (AFC) in predicting live birth outcomes. The study involved 603 women undergoing in vitro fertilization (IVF) using the long protocol for controlled ovarian hyperstimulation (COH). Serum levels of AMH, FSH and inhibin B as well as AFC were measured on the first three days of the menstrual cycle prior to the beginning of stimulation. AMH was the only independent parameter that correlated with the chance of live birth. We found that live birth rates of 46.2% (patient age <35 years), 44.7% (35–37 years), 32.1% (38–39) and 15.3% (>39) were associated with concentrations of AMH > 1.4 ng/ml. For the AMH range 0.6–1.4 ng/ml, the live birth rates were 29.3%, 12.5%, 5.6% and 2.7%, respectively, and for AMH concentrations below 0.6 ng/ml the rates were 7.1%, 8.3%, 0% and 5.8%, respectively. Independently of other parameters affecting the chance of live birth, the success rate was the highest when the AMH level was >2 ng/ml, significantly lower when the AMH concentration was about 1 ng/ml, and 0% when the AMH concentration was ∼0.1 ng/ml. In conclusion, this is the first report to demonstrate that AMH level correlated better than age, FSH or inhibin B concentrations or AFC with live birth outcome. Therefore, the basal serum concentration of AMH may become a new, substantial prognostic factor regarding live birth above and beyond other currently available predictors of IVF outcome.     

Elective frozen-thawed embryo transfer (FET) in women at risk for ovarian hyperstimulation syndrome

Elective cryopreservation of cultured embryos has become a treatment option for women at risk for ovarian hyperstimulation syndrome (OHSS). The aim of our study was to investigate the outcome of elective cryopreservation and consecutive frozen-thawed embryo transfer (FET) in a large IVF clinic in Austria. A total of 6104 controlled ovarian hyperstimulation cycles (COH) were performed on 2998 patients including 200 patients (6.7%) who were undergoing elective cryopreservation and FET due to high risk of OHSS. We estimated the cumulative live birth rate using the Kaplan-Meier method and evaluated independent predictors for successful live births with a Cox model. A total of 270 frozen-thawed embryo transfers were performed on 200 patients with up to 4 transfers per patient. The first embryo transfer showed a live birth rate of 42.0%, the second transfer showed a cumulative rate of 58.5%. After a total of 4 FETs from the same COH cycle, a cumulative live birth rate of 61.0% per COH cycle could be achieved. Four cases of OHSS occurred amongst these patients (2.0%), all of them of moderate severity. Multivariate analysis identified maternal age, the use of assisted hatching and the number of embryos transferred at the blastocyst stage as independent predictors for cumulative live birth. Our study clearly suggests that elective FET is safe and shows excellent cumulative live birth rates. This concept can, therefore, be used to avoid the severe adverse events caused by COH and the inefficient use of cultured embryos.     

Performance of the AutoPap Primary Screening System in the detection of high-risk cases in cervicovaginal smears

OBJECTIVE: To assess the performance of the AutoPap Primary Screening System (APSS) (TriPath Imaging, Inc., Burlington, North Carolina, U.S.A.) for the detection of high grade cervical squamous intraepithelial lesions and invasive cervical cancer. STUDY DESIGN: A total of 14,779 consecutive conventional Pap smears were processed by the APSS. All slides designated as "Review" by the device were manually screened according to the Bethesda System. The ranking scores obtained from the device were compared with the cytologic interpretations in all cases and with the final histologic diagnoses in the cases with cytologic severe abnormalities. RESULTS: The device classified 10,349 slides as Review (78%) and 2,912 (22%) as "No Further Review." In the 78% Review cases, the samples were ranked in descending order of potential abnormality, broken into quintiles. The correlation between the slide quintile ranks and the manual cytologic diagnosis indicated that 90% of abnormal smears were categorized by the device as in the first and second quintile rank, and the correlation between the rank report of the device and the histologic diagnosis showed that all cases of HSIL or invasive carcinoma were in the top two ranks. No significant abnormalities were observed in any of the smears categorized as No Further Review. CONCLUSION: This study confirmed the effectiveness of APSS for the detection of Pap smears with severe abnormalities.