Letrozole versus clomiphene for infertility in the polycystic ovary syndrome.

Background: Clomiphene is the current first-line infertility treatment in women with the polycystic ovary syndrome, but aromatase inhibitors, including letrozole, might result in better pregnancy outcomes.

Methods: In this double-blind, multicenter trial, we randomly assigned 750 women, in a 1:1 ratio, to receive letrozole or clomiphene for up to five treatment cycles, with visits to determine ovulation and pregnancy, followed by tracking of pregnancies. The polycystic ovary syndrome was defined according to modified Rotterdam criteria (anovulation with either hyperandrogenism or polycystic ovaries).

Meta-analysis of loci associated with age at natural menopause in African-American women.

Age at menopause marks the end of a woman's reproductive life and its timing associates with risks for cancer, cardiovascular and bone disorders. GWAS and candidate gene studies conducted in women of European ancestry have identified 27 loci associated with age at menopause. The relevance of these loci to women of African ancestry has not been previously studied.

The Pregnancy in Polycystic Ovary Syndrome II study: baseline characteristics and effects of obesity from a multicenter randomized clinical trial.

Objective: To summarize baseline characteristics from a large multicenter infertility clinical trial.

Design: Cross-sectional baseline data from a double-blind randomized trial of two treatment regimens (letrozole vs. clomiphene).

The Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial: rationale and design of a double-blind randomized trial of clomiphene citrate and letrozole for the treatment of infertility in women with polycystic ovary syndrome.

Polycystic Ovary Syndrome (PCOS) is a common cause of female infertility and first line treatment is currently oral clomiphene citrate, a selective estrogen receptor modulator, which results in both a high nonresponse rate and multiple pregnancy rate. Aromatase inhibitors such as letrozole may have more favorable ovarian and endometrial effects. The goal of the Pregnancy in Polycystic Ovary Syndrome II (PPCOSII) study is to determine the safety and efficacy of clomiphene citrate (CC) compared to letrozole, in achieving live birth in infertile women with PCOS.

Replication of loci influencing ages at menarche and menopause in Hispanic women: the Women's Health Initiative SHARe Study.

Several genome-wide studies have identified loci associated with reproductive traits, such as ages of menarche and menopause, in women of European ancestry. In this study, we investigated the relevance of these loci in minority US Hispanic women. We utilized data from 3468 women who were genotyped as a part of the Women's Health Initiative SNP Health Association Resource.

Recruitment challenges of a multicenter randomized controlled varicocelectomy trial.

Objective: To review reasons for suboptimal recruitment for a randomized controlled trial (RCT) of varicocelectomy versus intrauterine insemination (IUI) for treatment of male infertility and to suggest means for improving future study recruitment.

Design: Survey of Reproductive Medicine Network (RMN) participating sites.

Setting: Reproductive Medicine Network.

Patterns and predictors of sexual activity among women in the Hormone Therapy trials of the Women's Health Initiative.

Objective: The aim of this study was to determine the patterns and predictors of sexual activity in the Hormone Therapy (HT) Trials of the Women's Health Initiative (WHI).

Methods: Sexual activity questions were administered to 27,347 women ages 50 to 79 years at baseline and at year 1 and to a random 8.6% subsample at years 3 and 6.

Proactively establishing a biologic specimens repository for large clinical trials: an idea whose time has come.

Large randomized clinical trials are becoming more costly, and resources to support them increasingly scarce. Biologic materials, such as blood, DNA, body fluids, or tissue samples collected and stored as a component of these studies represent an invaluable resource, to answer immediate secondary hypotheses, but also as archived material, linked to the study data, for the use of investigators long into the future. The regulatory climate surrounding the storage and future unconstrained utilization of biologic materials is evolving quickly.

Establishing a biologic specimens repository for reproductive clinical trials: technical aspects.

The individual research group or independent investigator often requires access to samples from a unique well characterized subject population. Cohorts of such samples from a well-defined comparative population are rare and limited access can impede progress. This bottleneck can be removed by accessing the samples provided by biorepositories such as the NIH/NICHD Cooperative Reproductive Medicine Network (RMN) Biorepository (detailed in the preceeding manuscript in this issue.

Serum beta human chorionic gonadotropin levels can inform outcome counseling after in vitro fertilization.

The predictive value of serum beta hCG level for fetal cardiac motion and pregnancy outcome after IVF was evaluated. The serum hCG level 12 days after ET is a useful predictor of subsequent presence of fetal cardiac activity and live birth and may assist clinicians in counseling patients regarding their IVF outcome.

In vitro fertilization outcomes in Hispanics versus non-Hispanic whites.

The in vitro fertilization (IVF) outcomes, including clinical intrauterine gestation rate and live birth rate, between Hispanic and non-Hispanic white women were compared, and there were no differences. Hispanics were more likely to have a diagnosis of tubal factor infertility, whereas non-Hispanic white women were more likely to have endometriosis as their infertility diagnosis.

Vasomotor symptoms and cardiovascular events in postmenopausal women.

Objective: Emerging evidence suggests that women with menopausal vasomotor symptoms (VMS) have increased cardiovascular disease (CVD) risk as measured by surrogate markers. We investigated the relationships between VMS and clinical CVD events and all-cause mortality in the Women's Health Initiative Observational Study (WHI-OS).

Methods: We compared the risk of incident CVD events and all-cause mortality between four groups of women (total N = 60,027): (1) no VMS at menopause onset and no VMS at WHI-OS enrollment (no VMS [referent group]), (2) VMS at menopause onset but not at WHI-OS enrollment (early VMS), (3) VMS at both menopause onset and WHI-OS enrollment (persistent VMS [early and late]), and (4) VMS at WHI-OS enrollment but not at menopause onset (late VMS).

Derivation and characterization of novel nonhuman primate embryonic stem cell lines from in vitro-fertilized baboon preimplantation embryos.

The development of nonhuman primate (NHP) embryonic stem cell (ESC) models holds great promise for cell-mediated treatment of debilitating diseases and to address numerous unanswered questions regarding the therapeutic efficacy of ESCs while supplanting ethical considerations involved with human studies. Here we report successful establishment and characterization of 3 novel baboon (Papio cynocephalus) ESC lines from the inner cell mass of intracytoplasmic sperm injection-derived blastocysts. Embryos were cultured in an improved baboon embryo in vitro culture protocol.

Total testosterone assays in women with polycystic ovary syndrome: precision and correlation with hirsutism.

Context: There is no standardized assay of testosterone in women. Liquid chromatography mass spectrometry (LC/MS) has been proposed as the preferable assay by an Endocrine Society Position Statement.

Objective: The aim was to compare assay results from a direct RIA with two LC/MS.

Decision trees for identifying predictors of treatment effectiveness in clinical trials and its application to ovulation in a study of women with polycystic ovary syndrome.

Background: Double-blind, randomized clinical trials are the preferred approach to demonstrating the effectiveness of one treatment against another. The comparison is, however, made on the average group effects. While patients and clinicians have always struggled to understand why patients respond differently to the same treatment, and while much hope has been held for the nascent field of predictive biomarkers (e.

Ovarian stimulation, in vitro fertilization, and effects of culture conditions on baboon preimplantation embryo development.

Objective: To evaluate the effects of ovarian stimulation and intracytoplasmic sperm injection (ICSI)-induced fertilization and efficacy of various culture systems on in vitro development of baboon embryos.

Design: In vitro study, animal model.

Setting: Research laboratory.

Psychosocial effects of physical and verbal abuse in postmenopausal women.

Purpose: The purpose of this study was to examine the psychological effects of physical and verbal abuse in a cohort of older women.

Methods: This observational cohort study was conducted at 40 clinical sites nationwide that are part of the Women's Health Initiative (WHI) Observational Study. We surveyed 93,676 women aged 50 to 79 years using the mental health subscales and the combined mental component summary (MCS) score of the RAND Medical Outcomes Study 36-item instrument.

Hormone therapy and physical function change among older women in the Women's Health Initiative: a randomized controlled trial.

Objective: Although estrogen may be linked to biological pathways that maintain higher physical function, the evidence is derived mostly from observational epidemiology and therefore has numerous limitations. We examined whether hormone therapy affected physical function in women 65 to 79 years of age at enrollment.

Methods: This study involves an analysis of the Women's Health Initiative randomized controlled trials of hormone therapy in which 922 nondisabled women who had previous hysterectomies were randomized to receive estrogen therapy or a placebo and 1,458 nondisabled women with intact uteri were randomized to receive estrogen + progestin therapy or a placebo.

Calcium plus vitamin D supplementation and the risk of colorectal cancer.

Background: Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking.

Methods: We conducted a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women's Health Initiative centers: 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [corrected] twice daily (1000 mg of elemental calcium and 400 IU of vitamin D3) and 18,106 received a matching placebo for an average of 7.

Calcium plus vitamin D supplementation and the risk of fractures.

Background: The efficacy of calcium with vitamin D supplementation for preventing hip and other fractures in healthy postmenopausal women remains equivocal.

Methods: We recruited 36,282 postmenopausal women, 50 to 79 years of age, who were already enrolled in a Women's Health Initiative (WHI) clinical trial. We randomly assigned participants to receive 1000 mg of elemental [corrected] calcium as calcium carbonate with 400 IU of vitamin D3 daily or placebo.

Low-fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial.

Context: Multiple epidemiologic studies and some trials have linked diet with cardiovascular disease (CVD) prevention, but long-term intervention data are needed.

Objective: To test the hypothesis that a dietary intervention, intended to be low in fat and high in vegetables, fruits, and grains to reduce cancer, would reduce CVD risk.

Design, Setting, And Participants: Randomized controlled trial of 48,835 postmenopausal women aged 50 to 79 years, of diverse backgrounds and ethnicities, who participated in the Women's Health Initiative Dietary Modification Trial.

Low-fat dietary pattern and risk of colorectal cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial.

Context: Observational studies and polyp recurrence trials are not conclusive regarding the effects of a low-fat dietary pattern on risk of colorectal cancer, necessitating a primary prevention trial.

Objective: To evaluate the effects of a low-fat eating pattern on risk of colorectal cancer in postmenopausal women.

Design, Setting, And Participants: The Women's Health Initiative Dietary Modification Trial, a randomized controlled trial conducted in 48,835 postmenopausal women aged 50 to 79 years recruited between 1993 and 1998 from 40 clinical centers throughout the United States.