Genetic causes and workup of male and female infertility

Studies show that the greatest check on human reproduction occurs prenatally in apparently fertile couples. Most chromosomally abnormal embryos are aborted spontaneously. This paper, to be published in three parts, reviews the major known anatomic, functional, genetic, and environmental causes of infertility and reproductive wastage. The second and third parts, to appear in succeeding issues, are concerned with chromosome abnormalities and congenital malformations in the period from birth to adult life and with the diagnostic workup of infertile men and women.     

Genetic Variation in Healthy Oldest-Old

Individuals who live to 85 and beyond without developing major age-related diseases may achieve this, in part, by lacking disease susceptibility factors, or by possessing resistance factors that enhance their ability to avoid disease and prolong lifespan. Healthy aging is a complex phenotype likely to be affected by both genetic and environmental factors. We sequenced 24 candidate healthy aging genes in DNA samples from 47 healthy individuals aged eighty-five years or older (the ‘oldest-old’), to characterize genetic variation that is present in this exceptional group. These healthy seniors were never diagnosed with cancer, cardiovascular disease, pulmonary disease, diabetes, or Alzheimer disease. We re-sequenced all exons, intron-exon boundaries and selected conserved non-coding sequences of candidate genes involved in aging-related processes, including dietary restriction (PPARG, PPARGC1A, SIRT1, SIRT3, UCP2, UCP3), metabolism (IGF1R, APOB, SCD), autophagy (BECN1, FRAP1), stem cell activation (NOTCH1, DLL1), tumor suppression (TP53, CDKN2A, ING1), DNA methylation (TRDMT1, DNMT3A, DNMT3B) Progeria syndromes (LMNA, ZMPSTE24, KL) and stress response (CRYAB, HSPB2). We detected 935 variants, including 848 single nucleotide polymorphisms (SNPs) and 87 insertion or deletions; 41% (385) were not recorded in dbSNP. This study is the first to present a comprehensive analysis of genetic variation in aging-related candidate genes in healthy oldest-old. These variants and especially our novel polymorphisms are valuable resources to test for genetic association in models of disease susceptibility or resistance. In addition, we propose an innovative tagSNP selection strategy that combines variants identified through gene re-sequencing- and HapMap-derived SNPs.     

Silencing of the DNA methyltransferase 1 associated protein 1 (DMAP1) gene in the invasive ladybird Harmonia axyridis implies a role of the DNA methyltransferase 1‐DMAP1 complex in female fecundity

The invasive harlequin ladybird Harmonia axyridis is a textbook example of polymorphism and polyphenism as the temperature during egg development determines the frequency of melanic morphs and the number and size of black spots in nonmelanic morphs. Recent concepts in evolutionary biology suggest that epigenetic mechanisms can translate environmental stimuli into heritable phenotypic changes. To investigate whether epigenetic mechanisms influence the penetrance and expressivity of colour morphs in H. axyridis, we used RNA interference to silence key enzymes required for DNA methylation and histone modification. We found that neither of these epigenetic mechanisms affected the frequency of different morphs, but there was a significant impact on life‐history traits such as longevity and fecundity. Strikingly, we found that silencing the gene encoding for DNA methyltransferase 1 associated protein 1 (DMAP1) severely reduced female fecundity, which correlated with an abundance of degenerated ovaries in DMAP1‐knockdown female beetles. Finally, we observed significant differences in DMAP1 expression when we compared native and invasive H. axyridis populations with a biocontrol strain differing in egg‐laying capacity, suggesting that the DNA methyltransferase 1‐DMAP1 complex may influence the invasive performance of this ladybird.     

Genetic Factors in Determining Bone Mass

This investigation was undertaken to evaluate possible genetic determinants of bone mass with the premise that inheritance of bone mass could be of etiologic importance in osteoporosis.Bone mass and width measurements were made with the photon absorption technique on the right radius of 71 juvenile and 80 adult twin paris. The variance of intrapair differences of bone mass in monozygotic (MZ) juvenile twins was 0.0013 g(2)/cm(2) compared to 0.0052 g(2)/cm(2) in the dizygotic (DZ) twins. For the adult twins the variance of intrapair differences in bone mass was 0.0069 for MZ and 0.0137 for DZ twins. Similar results were obtained for bone width. The significantly larger variation in intrapair differences in DZ twins indicates that these traits have significant genetic determinants. These intrapair differences were found to increase with age, suggesting that genetic-environmental interaction also contributes to the observed variation in bone mass.These data provide evidence that bone mass does have significant genetic factors, which alone or in conjunction with environmental factors may predispose persons to the development of osteoporosis.     

Eggshells of <Emphasis Type="Italic">Drosophila melanogaster</Emphasis> and <Emphasis Type="Italic">D. simulans</Emphasis>: Ultrastructure,Measurement and Analyses

Phenotypic divergence of eggshells between D. melanogaster and D. simulans strains, was compared, using SEM, for analyzing fitness related eco-physiological traits of the eggshells in the two sibling species. The variations of eggshell traits between strains within species, between species and asymmetry in hybrids of two species have been calculated for understanding the demographic success of the two species. The present results revealed that variation of traits between strains within species was not always same which suggest that many traits are not strongly constrained within species. The main findings show that following eco-physiological traits of eggshells are mostly diverged between two species: (i) dorsal appendages (DA) length, (ii) insertion position of DA in main body of eggshell, (iii) the number and size of respiratory pores in dorsal and ventral side of DA, (iv) average length and volume of eggshells and (v) the thickness of chorionic hexagonal ridges. Examination of interspecific hybrids showed that the traits have undergone considerable genetic changes during evolutionary divergence of the two species. The authors propose that divergent ovipositional preference of the females of two species, may be the driving force in establishing species specific life history parameters for avoiding competition at pre-adult stages and demographic success.     

Genetic Loci implicated in erythroid differentiation and cell cycle regulation are associated with red blood cell traits

ObjectiveTo identify common genetic variants influencing red blood cell (RBC) traits.Patients and MethodsWe performed a genomewide association study from June 2008 through July 2011 of hemoglobin, hematocrit, RBC count, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration in 12,486 patients of European ancestry from the electronic MEdical Records and Genomics (eMERGE) network. We developed an electronic medical record–based algorithm that included individuals who had RBC measurements obtained for clinical care and excluded values measured in the setting of hematopoietic disorders, comorbid conditions, or medications known to affect RBC production or a recent history of blood loss.ResultsWe identified 4 new genetic loci and replicated 11 loci previously reported to be associated with one or more RBC traits in individuals of European ancestry. Notably, genes present in 3 of the 4 newly identified loci (THRB, PTPLAD1, CDT1) and in 6 of the 11 replicated loci (KLF1, ALDH8A1, CCND3, SPTA1, FBXO7, TFR2/EPO) are implicated in erythroid differentiation and regulation of cell cycle in hematopoietic stem cells.ConclusionGenes in the erythroid differentiation and cell cycle regulation pathways influence interindividual variation in RBC indices. Our results provide insights into the molecular basis underlying variation in RBC traits.     

Genetic variations and transplant outcomes

Extensive genetic variation has been described in molecules regulating innate and adaptive immunity, pharmacokinetics, coagulation, and fibrosis. However, large prospective studies need to be performed to define the clinical consequences of such variation and the potential benefits of genotyping these markers for patients. The purpose of this review is to summarize recent data describing associations of polymorphisms in both immunological and non-immunological molecules with transplant outcomes, and discuss their clinical implications and limitations.     

Portrait of an oocyte: our obscure origin

Oocytes play a pivotal role in the cycle of human life. As we discuss here, after emerging from germline stem cells in the fetus, they grow in a follicular niche in which development is harmonized for timely ovulation and hormone secretion after puberty. Most human oocytes have poor developmental competence and are peculiarly vulnerable to chromosomal malsegregation, especially as women pass the optimal years of fertility and may begin to turn to assisted reproductive technologies (ARTs) and egg donation. Research needs to focus on the molecular factors involved and the environmental niche required for optimal development of oocytes, with the aim of increasing their numbers and quality for ARTs, since these are the factors that so often limit human fertility.Eggs have fascinated philosophers and scientists ever since Aristotle pondered the mysteries of chick development, but the minute mammalian egg remained elusive until von Baer’s discovery in 1826 (1). Subsequently, the creation of haploid gametes through meiosis and their union by fertilization were observed and understood by successive generations of biologists (2). While the spermatozoon makes a complementary genetic contribution to the zygote, the oocyte is obviously its major cytoplasmic donor, contributing nearly all the organelles and nonchromosomal molecules needed for development. Although fertilization marks the debut of a new genetic entity, it is abundantly clear that embryogenesis is deeply rooted in oogenesis. Oocytes are highly specialized to undergo the unique processes of meiosis and fertilization and to execute a molecular program for development. Upon fertilization, their reproductive role is achieved through formation of blastomeres, the cells produced by the first cleavage divisions of the fertilized oocyte that are the precursors of all cell lineages in the fetus and its membranes. Oocytes are therefore highly differentiated and the mothers of totipotent cells at the same time, a paradox we address later (see Molecular program for development below). But it is not just their amazing biology that drives scientific curiosity — they set limits on the reproductive lifespan of a woman, are very common causes of infertility, and contribute to major birth defects, including Down syndrome. Unfortunately, research is hindered by their extreme rarity and by greater bioethical constraints than with any other cell type, except products of their fertilization. Until oocytes were harvested routinely for in vitro fertilization (IVF), beginning in the early 1980s, few gynecologists had ever seen a living female gamete from our species. Although IVF procedures are common and ovarian stimulation is standard practice, oocytes remain very scarce and precious. Moreover, the great majority of oocytes donated to research come from IVF programs in which they failed to be fertilized or were immature, and only rarely do freshly harvested cells presumed to be mature and fertile become available for study. Such drawbacks are compounded by a postovulatory lifespan of only one day at most, and by the inability to propagate oocytes, as can be done with cell lines. Progress has therefore depended on animal models, including nonmammalian species, despite differences in the size and polarity of eggs. The cytoplasm of human oocytes appears relatively uniform, as we shall explain, and this has huge implications for invasive assisted reproductive technology (ARTs) such as intracytoplasmic sperm injection (ICSI), in which a single sperm is injected into the cytoplasm of an oocyte to treat most forms of male infertility, and embryo biopsy for preimplantation genetic diagnosis, in which one cell is removed for genetic diagnosis and/or screening for aneuploidy. Materials deposited during oogenesis visibly polarize the eggs of amphibians, flies, and many other animals, determine the plane of the first cleavage division, and become sequestered in specific early lineages of the embryo. Another notable difference between species is the absence of germline stem cells in mammals, or at least active ones, after birth, and ovaries are generally believed to eke out a dwindling endowment of nonrenewable oocytes during adulthood. The fecundity of human ovaries is more constrained than in most other species because the store of oocytes is exhausted by mid-life (i.e., menopause). Moreover, oocyte fertility starts to decline precipitately early in mid-life (beginning when women are approximately 30 years old), when aneuploidy becomes remarkably prevalent (3). Since rapid ovarian aging is universal in our species, an evolutionary explanation is called for. Oocytes harvested for IVF or at ovulation are arrested at metaphase II in a cloud of “cumulus” cells, a subpopulation of granulosa cells in the follicle whose main functions are to support oocyte development and to contribute to hormone and growth factor production. This is the final stage of a long, complex history beginning with primordial germ cells in the epiblast of an implanting embryo (4). After multiplying and migrating to the gonadal anlagen, they continue to undergo mitosis until entering meiotic prophase, so that at birth virtually the entire 1–2 million germ cells, now called oocytes, have reached the diplotene stage of prophase I (5). They have therefore already undergone meiotic recombination, so that each oocyte has a unique genetic constitution, and they become enveloped in a layer of pregranulosa cells to form primordial follicles. But they cannot ovulate, resume meiosis, or undergo fertilization until after several weeks of growth in the follicle, which enlarges from the primordial stage (approximately 35 microns diameter) to the grape-sized Graafian stage that is ripe for ovulation. In this Review we consider oocyte development across the entire span of follicle growth.     

Influence of Abuse History on Concurrent Benzodiazepine and Opioid Use in Chronic Pain Patients

An important predictor of opioid overdose is co-use of benzodiazepines, which are often prescribed for anxiety. Coping with anxiety may be particularly difficult among individuals with a history of abuse, as it is often linked to higher pain severity and poorer coping skills. We explored whether abuse history moderated the association between anxiety and benzodiazepine use among current opioid users. New patients at a tertiary care, outpatient pain clinic completed self-report measures of medication use, anxiety, and physical and sexual abuse history (child abuse only, adult abuse only, or cumulative abuse). The present study included adult patients reporting current opioid use (n?=?1,785). Approximately 16% reported co-use of benzodiazepines, and 17% reported a history of abuse. Patients reporting child abuse only and cumulative abuse reported co-use of benzodiazepines and opioids more often than those denying abuse and patients reporting adult abuse only (P < .001). Multivariate logistic regression analyses showed that the probability of benzodiazepine use among patients reporting cumulative abuse increased sharply at high levels of anxiety (P?=?.003). Cumulative abuse may increase sensitivity to psychological distress and put patients at risk for co-use. Providers should be aware of life history factors, including abuse, that may drive the need for medication.Perspective: This article examines the association between history of abuse victimization and co-use of benzodiazepines among chronic pain patients reporting current opioid use. The findings suggest that cumulative victimization across the lifespan may contribute to co-use by increasing sensitivity to psychological or physical distress or by negatively impacting coping skills.     

Genetic determinants of diabetic nephropathy

Diabetic nephropathy is the most serious complication of diabetes mellitus. Progression of the condition leads to end-stage renal failure, and other complications of diabetes are also common in this group of patients. The onset of overt albuminuria in a patient with diabetes heralds an increased risk of death, particularly from cardiovascular disease. There is considerable evidence to show that nephropathy is influenced by genetic factors. Epidemiological studies show that only a minority of patients with diabetes develop nephropathy irrespective of glycaemic control, suggesting that a subgroup of patients are at higher risk of nephropathy. Marked ethnic variation is observed, with nephropathy being more common in certain ethnic groups. Familial clustering of nephropathy is also observed. Parental history of hypertension, diabetes or cardiovascular disease appears to predispose to nephropathy in patients with diabetes. A number of methods are available to dissect polygenic disease: animal models, genetic association studies (case-control studies), affected sib-pair studies, discordant sib-pair studies and transmission distortion analysis. Most published work has been based on association studies. Association studies have shown conflicting results often due to small numbers of cases and controls, and poor phenotypic characterization. The angiotensin-converting enzyme gene insertion (I)/deletion (D) polymorphism has been studied in detail, but does not appear to be a strong risk marker for nephropathy. It does, however, appear to have a role in response to angiotensin-converting enzyme inhibition, with II homozygotes being the most responsive and DD homozygotes the least. A number of other genetic loci have also shown positive associations with nephropathy, including apolipoprotein E, heparan sulphate and aldose reductase. More recently, affected sib-pair analysis and discordant sib-pair analysis have suggested possible genetic loci on chromosomes 3, 7, 9, 12 and 20. These have yet to be reproduced in larger numbers of families, and the specific gene regions on these chromosomes remain elusive. The evidence presented in this review strongly supports the role of genetic factors in nephropathy. Detection of strong genetic risk markers for nephropathy will allow further insights into the pathogenesis of nephropathy, and possibly the development of novel therapeutic agents for its treatment. It will also allow preventive therapy to be directed at those patients with the greatest risk for development of diabetic nephropathy.     

The Effect of Diet Quality and Wing Morph on Male and Female Reproductive Investment in a Nuptial Feeding Ground Cricket

A common approach in the study of life-history trade-off evolution is to manipulate the nutrient content of diets during the life of an individual in order observe how the acquisition of resources influences the relationship between reproduction, lifespan and other life-history parameters such as dispersal. Here, we manipulate the quality of diet that replicate laboratory populations received as a thorough test of how diet quality influences the life-history trade-offs associated with reproductive investment in a nuptial feeding Australian ground cricket (Pteronemobius sp.). In this species, both males and females make significant contributions to the production of offspring, as males provide a nuptial gift by allowing females to chew on a modified tibial spur during copulation and feed directing on their haemolymph. Individuals also have two distinct wing morphs, a short-winged flightless morph and a long-winged morph that has the ability to disperse. By manipulating the quality of diet over seven generations, we found that the reproductive investment of males and females were affected differently by the diet quality treatment and wing morph of the individual. We discuss the broader implications of these findings including the differences in how males and females balance current and future reproductive effort in nuptial feeding insects, the changing nature of sexual selection when diets vary, and how the life-history trade-offs associated with the ability to disperse are expected to differ among populations.     

Genetic variations within the insulin gene region are associated with accelerated fetal growth

Size at birth has been proposed to be associated with the risk of type 2 diabetes and cardiovascular disease later in life. It is, however, unclear whether this association is attributed to an unfavorable intrauterine environment or to specific genotypes predisposing both altered fetal growth and common diseases in adult life. The aim of this study was to investigate the associations between the neonatal birth size and the genotypes of polymorphic loci within the insulin gene (INS) region, which is susceptible to diabetes mellitus. We analyzed the genotypes of two polymorphic loci; -23HphI and HUMTH01, in 520 pairs of normal Japanese mothers and their neonates, and compared with the somatoscopic characteristics at birth converted into standard deviation scores (SDS) according to sex, parity and gestational weeks at delivery. It was revealed that neonatal -23HphI T allele and HUMTH01 allele10, which are linked to the INS variable number of tandem repeats (VNTR) class III allele, were associated with increased weight, head circumstance, and length at birth. These associations confirmed that variation within the INS region, most probably at the INS-VNTR, influences fetal growth. Furthermore, the finding that the paternally transmitted -23HphI T allele was exclusively correlated with increased size at birth indicates the involvement of an imprinting mechanism. In conclusion, the INS-VNTR class III allele might accelerate fetal growth in a parent-specific manner.     

Genetic covariation between serum gamma-glutamyltransferase activity and cardiovascular risk factors

BACKGROUND: Several studies have shown that variation in serum gamma-glutamyltransferase (GGT) in the population is associated with risk of death or development of cardiovascular disease, type 2 diabetes, stroke, or hypertension. This association is only partly explained by associations between GGT and recognized risk factors. Our aim was to estimate the relative importance of genetic and environmental sources of variation in GGT as well as genetic and environmental sources of covariation between GGT and other liver enzymes and markers of cardiovascular risk in adult twin pairs. METHODS: We recruited 1134 men and 2241 women through the Australian Twin Registry. Data were collected through mailed questionnaires, telephone interviews, and by analysis of blood samples. Sources of variation in GGT, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) and of covariation between GGT and cardiovascular risk factors were assessed by maximum-likelihood model-fitting. RESULTS: Serum GGT, ALT, and AST were affected by additive genetic and nonshared environmental factors, with heritabilities estimated at 0.52, 0.48, and 0.32, respectively. One-half of the genetic variance in GGT was shared with ALT, AST, or both. There were highly significant correlations between GGT and body mass index; serum lipids, lipoproteins, glucose, and insulin; and blood pressure. These correlations were more attributable to genes that affect both GGT and known cardiovascular risk factors than to environmental factors. CONCLUSIONS: Variation in serum enzymes that reflect liver function showed significant genetic effects, and there was evidence that both genetic and environmental factors that affect these enzymes can also affect cardiovascular risk.     

Sex differences in lifetime prevalence of low back pain: A multinational study of opposite-sex twin pairs

Background

Low back pain (LBP) is more likely to occur in people with a family history of this condition, highlighting the importance of accounting for familial factors when studying the individual risk of LBP. We conducted a study of opposite-sex twin pairs investigating sex differences in LBP while accounting for (genetic and shared environmental) familial factors.

Methods

We applied a matched co-twin control design to study 795 adult opposite-sex pairs from Australia, Spain, and the United States (US). We used mixed-effects logistic regression to assess the within-pair association between female sex and lifetime prevalence of LBP in unadjusted and adjusted models for body-mass-index, and depression, as well as interactions between female sex and age (<median age vs. ≥median age) in this association.

Results

The mean age of the sample was 47.4 years (Standard Deviation = 16.5). The adjusted odds ratio (aOR) of the association between sex and LBP in the merged sample was 1.11 (95% Confidence Interval = 0.88–1.40), with 87.4% of the variance in the studied association explained by between-site heterogeneity (Q test; p = 0.001). Females had 2.37 (95% CI: 1.48–3.78) higher odds of LBP compared to their male co-twins in the Spanish sample (adjusted), but a sex association was not found in the Australian nor US samples.

Conclusions

We found no evidence of the association between sex and LBP in our merged sample. Between-population differences (i.e. cultural background or health system characteristics) are likely to be major factors leading to variation in the sex association with LBP when familial factors are accounted for.

Significance

Our study of adult opposite-sex twin pairs found no evidence of an association between female sex and lifetime prevalence of low back pain after controlling for familial factors in the merged sample from Australia, Spain and USA, contrary to findings from previous studies of unrelated individuals. Our findings indicate potentially relevant between-country genetic, cultural and environmental differences which may need to be considered for optimal and individualized strategies for the prevention and management of low back pain across the lifespan.     

Variations in serum iron and total iron binding capacity with the time of intake of combined oral contraceptives.

Serum iron and total iron binding capacity (TIBC) were estimated in 145 healthy subjects in the reproductive stage of life, using lyndiol and eugynone for a period of 1-72 months, and results were compared with those of 30 healthy individuals, of the same class, also in reproductive stage of life. Serum iron variation did not follow any clear pattern. TIBC increased in 80% of the subjects to a value equivalent to 3-110% of the mean control. There was also a clear increase observed in immunoelectrophoretic pattern of transferrin, following the use of oral contraceptives.     

Ethical Aspects of Genetic Screening

Public and professional concern associated with the idea of genetic screening has generated numerous publications on the ethics of genetic screening (e.g. 1–4). Concerns revolve around inadequate consultation before screening is carried out, the unearthing of worrying risks, the use of genetic information in ways that could be disadvantageous to the person involved, stigma, and a phenomenon known as the ‘technological imperative’, which means that simply because a technology is available there is a tendency to use it. Most reports agree that, in practice, the main ethical problems are likely to involve screening for risk of common diseases of adult life, because of the possible impact on a person's healthy self-image, implications for health and life insurance, and the possibility of commercial exploitation of people who know themselves to be vulnerable.

In this paper I do not propose to address these issues directly. I have been invited to discuss this subject as a clinician involved with genetic screening, counselling and prenatal diagnosis for the haemoglobin disorders, the most common serious human recessively inherited diseases. Since we are scientists, any recommendations we make should be based on experience: my aim is to show that experience is often surprising, and that it is often possible to meet public concerns by taking quite simple practical steps.     

Genetic and environmental influences on plasma homocysteine: results from a Danish twin study

BACKGROUND: Increased plasma homocysteine has been linked to many clinical conditions including atherosclerosis and ischemic stroke. We assessed the genetic and environmental influences on homocysteine in adult twins and tested the influence of 3 candidate polymorphisms. METHODS: Homocysteine was analyzed in 1206 healthy twins, who were genotyped for 3 polymorphisms: MTHFR 677C>T, MTR 2756A>G, and NNMT (dbSNP: rs694539). To perform quantitative trait linkage analysis of the MTHFR locus, the genotyping was supplemented with 2 genetic markers localized on each site of the MTHFR locus. The twin data were analyzed using biometric structural equation models as well as a combined association and linkage analysis in 2 age cohorts. RESULTS: Age, sex, and MTHFR genotype have a significant impact on homocysteine concentrations, whereas the other genotypes were not associated with homocysteine concentrations. The variance in homocysteine could be solely ascribed to additive genetic and nonshared environmental factors, with an estimated additive genetic proportion of total variation at age 18-39 years of 0.63 (95% CI, 0.53-0.71) and at age 40-65 years of 0.27 (95% CI, 0.10-0.41). The impact of the MTHFR locus is estimated to explain 53% (95% CI, 0.07-0.67) of the total phenotypic variation in persons 18-39 years old and 24% (95% CI, 0.00-0.39) in persons 40-65 years old, i.e., almost all additive genetic variance. CONCLUSIONS: Homocysteine concentrations have a high heritability that decreases with age. The MTHFR gene locus is responsible for almost all the variation attributable to genetic factors, leaving very little influence of other genetic variations.     

Women's patterns of provider use across the lifespan and satisfaction with primary care coordination and comprehensiveness

BACKGROUND: Women have different patterns of provider use across the lifespan, but few studies have investigated women's evaluations of their primary care providers at different ages. OBJECTIVE: We sought to investigate the relationship between patterns of regular provider use and women's satisfaction with primary care across the lifespan. RESEARCH DESIGN: A sample of 1197 women ages 18 to 87 making primary health care visits was surveyed. Satisfaction with primary care in the past year was measured with a subscale the Care Coordination and Comprehensiveness subscale of the Primary Care Satisfaction Survey for Women (PCSSW). Bivariate comparisons and age stratified multivariate ordinal logistic regression models were estimated. RESULTS: Women in their early reproductive years (ages 18 to 34) are more satisfied with care coordination and comprehensiveness when their regular provider is a reproductive health specialist, primarily obstetrician gynecologist (ob/gyn) physicians. The odds of higher satisfaction are reduced with a generalist regular provider (OR = 0.38, P < 0.01), a generalist regular provider plus an ob/gyn (OR = 0.47, P < 0.05), or no regular provider (OR = 0.52, P < 0.05). The pattern of regular provider use is not significantly associated with satisfaction for women in other age categories. CONCLUSIONS: Most adult women see generalists for their primary health care, either alone or in combination with ob/gyns. Among younger women satisfaction is higher when an ob/gyn is the regular provider. Further research must consider women's perspectives on their provider use patterns and the appropriate role of ob/gyns in women's primary care across the lifespan.     

Psychosocial Issues Associated with Genetic Testing in Cystic Fibrosis Newborn Screening

The purpose of the study was to examine the experience of predictive genetic testing for hereditary breast and ovarian cancer (HBOC) and to compare experiences of younger women (≤ 35 years old) to the older study cohort (36–60 years old).
Grounded theory was used to examine the phenomenon of adults choosing to have predictive genetic testing for HBOC. A sample of 19 women, ten ≤ 35 years old was recruited through community and internet support group announcements. Semi-structured interviews were conducted in-person, by telephone or E-mail: according to participant preference.
Young women's experiences were different particularly around concerns about: (i) career plans, (ii) reproduction, and (iii) intimate relationships. Other concerns not specific to young women but also described included: (i) family relationships, (ii) fears of personal mortality, (iii) life and health insurance, and (iv) health information needs.
A commonly voiced experience specific to the young adult age group was feeling 'out-of-place' in the oncology clinics and support groups which participants perceived as being focused on concerns of older women. Further study may clarify the extent and nature of informational, emotional, social and decision support needs that are unique to this young adult population.