Infertility Cohort Research Articles

Type 1 diabetes risk in children born to women with fertility problems: a cohort study in 1.5 million Danish children.

While some studies have indicated that children born following fertility treatment are at an increased risk for insulin resistance and higher blood glucose levels, no study to date has investigated the risk of type 1 diabetes. In this large population-based cohort study we aim to assess the association between maternal fertility problems and the risk of type 1 diabetes in children. Information on all children, born in Denmark from 1987 to 2010, was extracted from the Civil Registration System and linked with the Danish Infertility Cohort to identify maternal fertility status. Diabetes information was obtained from the National Patient Register and the Childhood Diabetes Register. A Cox proportional hazard model was used to calculate hazard ratios and 95% confidence intervals. A total of 1 550 519 children made up the study cohort, of whom 110 393 (7.1%) were born to women with fertility problems. In all, 313 children born to women with fertility problems (0.36%) and 5176 children born to women without fertility problems (0.28%) were diagnosed with type 1 diabetes. The risk of type 1 diabetes was not affected by maternal fertility status (hazard ratio 1.01, 95% CI 0.90-1.13) when taking into account birth year, sex, history of parental diabetes, parental age and age at diagnosis. Our results showed no association between maternal fertility problems and risk of type 1 diabetes in children.

Fertility problems and risk of gestational diabetes mellitus: a nationwide cohort study

To determine whether women with a history of fertility problems have a higher risk of gestational diabetes mellitus (GDM) than women without a history of fertility problems after adjustment for maternal factors. Nationwide population-based cohort study. Not applicable. All live and stillbirths during 2004-2010 among women with fertility problems (n = 49,616) and women without fertility problems (n = 323,061) were identified by linkage between the Danish Medical Birth Registry and the Danish Infertility Cohort. Information on GDM was obtained from the Danish National Patient Registry. None. Odds ratios and 95% confidence intervals for the association between fertility problems and risk of GDM after adjustment for potentially confounding factors, including maternal age, prepregnancy BMI, parity, parental history of diabetes, level of education, and smoking during pregnancy. In total, 7,433 (2%) pregnant women received a diagnosis of GDM. Multivariate analysis showed that pregnant women with a history of fertility problems had a statistically significantly higher risk of GDM than pregnant women without fertility problems. In stratified analyses, the association between fertility problems and risk of GDM attenuated with increasing age and was more pronounced among primiparous women and women with polycystic ovary syndrome. Our findings suggest that pregnant women with a history of fertility problems are at increased risk of GDM.

Mental disorders in childhood and young adulthood among children born to women with fertility problems.

Is the risk of hospital admission or outpatient contact for mental disorders increased in children born to women with fertility problems compared with children born to women without fertility problems? We found an increased risk of hospital admission or outpatient contact for mental disorders in children born to women with fertility problems. Few studies have investigated the risk of mental disorders in children born after fertility treatment and although some studies have pointed to an increased risk, others found no association. The inconsistent results may be due to methodological constraints in many previous studies, including small sample size and short follow-up, resulting in imprecise risk estimates and lack of information on risk patterns of mental disorders in adulthood. This nationwide retrospective register-based cohort study included all 2 412 721 children born in Denmark between 1969 and 2006. All children were followed from date of birth until date of hospital contact for a mental disorder, date of emigration, date of death or 31 December 2009, whichever occurred first. Information concerning maternal fertility status for all children in the cohort was obtained by linkage to the Danish Infertility Cohort, which contains data on nearly all women with fertility problems in Denmark since 1963. A total of 124 269 (5%) children were born to women with fertility problems and 2 288 452 (95%) to women without fertility problems. To identify children hospitalized for a mental disorder, the cohort was linked to the Danish Psychiatric Central Research Registry. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between maternal fertility status and the risk of hospital admission or outpatient contact for various groups of mental disorders, including any mental disorder and all 11 main discharge diagnostic groups, classified according to the International Classification of Diseases, version 10. During a mean follow-up period of 21 years (range, 0-40 years), 168 686 (7%) children were admitted to hospital or had an outpatient contact for a mental disorder. Children born to women with fertility problems had a significantly higher risk of any mental disorder (HR 1.23; 95% CI 1.20-1.26) and for most of the 11 main discharge groups, including schizophrenia (HR 1.16; 95% CI 1.07-1.27), mood (affective) disorders (HR 1.21; 95% CI 1.15-1.28) and disorders of psychological development (HR 1.15; 95% CI 1.09-1.21) as well as the subgroup of attention-deficit/hyperactivity disorders (HR 1.36; 95% CI 1.29-1.45) compared with children born to women without fertility problems. The risk estimates did not change markedly when analyses were performed separately for mental disorders diagnosed during childhood (0-19 years) and in young adulthood (20-40 years). The true risk of mental disorders may be somewhat underestimated, as only severe disorders requiring hospital admission or outpatient contact were considered as events. Furthermore, we could not determine whether the increased risks observed were due to factors related to the underlying infertility or to fertility treatment procedures. This is the first report on mental disorders in adulthood among children born to women with fertility problems. Furthermore, we have assessed the risk of several severe mental disorders not previously studied (e.g. neurotic, stress-related and somatoform disorders and disorders of adult personality and behaviour). These important findings should be investigated further in large epidemiological studies designed to differentiate between factors related to fertility treatment and to the underlying infertility. The study was supported by internal funding from the Unit of Virus, Lifestyle and Genes at the Danish Cancer Society Research Center. All authors report no conflicts of interest.

Prospective study of a Swedish infertile cohort 2005-08: population characteristics, treatments and pregnancy rates

We here report on results from a prospective study comprising 380 infertile couples undergoing infertility work-up and various treatments for infertility in our clinic. The aim was to investigate the overall birth rate as a result of different treatments, as well as spontaneous pregnancies. Three hundred and eighty couples were consecutively included between December 2005 and May 2008. All couples underwent a fertility work-up, including hysterosalpingogram, hormonal characterization, clinical examination, screening for infectious diseases and semen analysis. The mean age of the women at the time of inclusion was 33.2 years. The mean duration of infertility prior to inclusion was 1.8 years. And 46.6% (n = 177) of the women had been pregnant prior to their first visit to the clinic and 30.0% (n = 114) had been pregnant earlier in their present relationship. As of November 2010, 57.3% (n = 218) of the women had given birth to a child when they were lost to follow up by the study. Spontaneous conception was observed in 11.3% (n = 43) of the women, 14.5% (n = 64) conceived after intrauterine insemination (IUI), 4.2% (n = 16) conceived after ovarian hyperstimulation and ovulation induction (OH/OI) and 28.4% (n = 113) after in vitro fertilization. There were 280 pregnancies and 58 spontaneous abortions (22.3%) in the group. Mean anti-mullerian hormone significantly correlated with antral follicle count and age and was significantly higher in the subgroup that became pregnant after IUI. Spontaneous pregnancies and IUI + OH/OI contributed significantly to the pregnancies observed in the total population. Predictive factors for pregnancy were anti-mullerian hormone in the group undergoing IUI treatment and in the age group ≥38-duration of infertility. Previous pregnancies, body mass index, estradiol, follicle stimulating hormone or having given birth prior to the infertility period were not predictive of pregnancy for the infertile couples in this study.

Array-based DNA methylation profiling in male infertility reveals allele-specific DNA methylation in PIWIL1 and PIWIL2

To identify CpG sites differentially methylated in peripheral blood of men with idiopathic infertility due to impaired spermatogenesis as compared with fertile controls. DNA methylation profiling on peripheral blood samples using the HumanMethylation450 BeadChip (Illumina) in patients and controls, single-nucleotide polymorphism (SNP) typing by Sanger sequencing. University institute in cooperation with genetic and infertility clinics. 30 infertile men with normal CFTR and AZF tests and karyotype, and 10 fertile male controls. None. DNA methylation levels at CpG sites. We identified 471 CpGs (287 genes) as differentially methylated between patients and controls. These were significantly enriched for the gene ontology functions MHC class II receptor activity and piwi-interacting (piRNA) binding. The latter was associated with two methylation-sensitive SNPs in the genes PIWIL1 and PIWIL2, respectively, which showed significant allele distribution skewing in the infertile cohort. We found that 445 (94.5%) of 471 differentially methylated CpGs were associated with SNPs, but 26 (15 genes) were not genomically templated, including the ENO1, MTA2, BRSK2, and LBX2 genes previously associated with fertility and spermatogenesis. Our study identifies surrogate DNA methylation markers for idiopathic infertility in peripheral blood and suggests that allele-specific DNA methylation differences at regulatory sites of genes involved in piRNA regulation are associated with disturbed spermatogenesis.

Out-of-Pocket Fertility Patient Expense: Data from a Multicenter Prospective Infertility Cohort

Out-of-Pocket Fertility Patient Expense: Data from a Multicenter Prospective Infertility Cohort

Out-of-Pocket Fertility Patient Expense: Data from a Multicenter Prospective Infertility Cohort

The high costs of fertility care may deter couples from seeking care. Urologists often are asked about the costs of these treatments. To our knowledge previous studies have not addressed the direct out-of-pocket costs to couples. We characterized these expenses in patients seeking fertility care. Couples were prospectively recruited from 8 community and academic reproductive endocrinology clinics. Each participating couple completed face-to-face or telephone interviews and cost diaries at study enrollment, and 4, 10 and 18 months of care. We determined overall out-of-pocket costs, in addition to relationships between out-of-pocket costs and treatment type, clinical outcomes and socioeconomic characteristics on multivariate linear regression analysis. A total of 332 couples completed cost diaries and had data available on treatment and outcomes. Average age was 36.8 and 35.6 years in men and women, respectively. Of this cohort 19% received noncycle based therapy, 4% used ovulation induction medication only, 22% underwent intrauterine insemination and 55% underwent invitro fertilization. The median overall out-of-pocket expense was $5,338 (IQR 1,197-19,840). Couples using medication only had the lowest median out-of-pocket expenses at $912 while those using invitro fertilization had the highest at $19,234. After multivariate adjustment the out-of-pocket expense was not significantly associated with successful pregnancy. On multivariate analysis couples treated with invitro fertilization spent an average of $15,435 more than those treated with intrauterine insemination. Couples spent about $6,955 for each additional invitro fertilization cycle. These data provide real-world estimates of out-of-pocket costs, which can be used to help couples plan for expenses that they may incur with treatment.

Ovulation-inducing drugs and ovarian cancer risk: results from an extended follow-up of a large United States infertility cohort

To examine the relationship of ovulation-inducing drugs and ovarian cancer. Retrospective cohort study, with additional follow-up since initial report. Five large reproductive endocrinology practices. In a retrospective cohort of 9,825 women evaluated for infertility at five clinical sites in the United States between 1965 and 1988 with follow-up through 2010, we examined the relationship of ovulation-inducing drugs and ovarian cancer (n = 85). None. Hazard rate ratios (RR) and 95% confidence intervals (CI) for ovarian cancer. Among women evaluated for infertility, there was no association of ovarian cancer risk with ever use of clomiphene citrate (CC) (adjusted RR 1.34, 95% CI 0.86-2.07) or gonadotropins (RR 1.00, 95% CI 0.48-2.08) and no evidence that any of several more detailed subgroups of usage were related to an increased risk with one exception: women who used CC and remained nulligravid did demonstrate much higher risks than those who successfully conceived compared with nonusers (respectively, RR 3.63, 95% CI 1.36-9.72 vs. RR 0.88, 95% CI 0.47-1.63). Our overall results were reassuring and consistent with other studies. A reason for an association between CC use and ovarian cancer among persistently nulligravid women remains to be determined. Given the large and increasing number of women treated with ovulation-inducing drugs, the increased risk of ovarian cancer among the subset of women who remained nulligravid should be further monitored.

A novel role for genomic copy number variants in female infertility

ObjectiveCopy number variants (CNVs) are genomic aberrations that alter the number of copies of genomic segments and therefore have the potential to alter dosage-sensitive genes and/or functional elements. Recent studies have shown that CNVs underlie various complex spectrum disorders and that the severity of the disorder is correlated with overall CNV burden. To investigate the role of CNVs in female infertility spectrum disorders, we have performed a survey examining CNVs in a cohort of patients with unexplained infertility.DesignRetrospective cohort of female patients with unexplained infertility.Materials and MethodsGenomic DNA extracted from blood samples was obtained from patients undergoing non-donor in-vitro fertilization (IVF) cycles at a large academic medical center. CNVs were detected using a custom NimbleGen Comparative Genomic Hybridization (CGH) Whole-Genome Tiling Array optimized for fertility-related loci. The resulting log2 ratios of the raw intensities were then normalized and segmented. The prevalence of CNVs among the infertile cohort was compared to the Children's Hospital of Philadelphia (CHOP) CNV database of healthy individuals.ResultsApproximately 30% of the >3000 CNVs detected were unique to the infertile patients (P<10-7, Binomial Test of Proportions). Moreover, CNVs specific to the infertile cohort appear to be overrepresented among regions of the genome predicted to play a role in mammalian fertility (P<10-16, t-test).ConclusionThe set of CNVs uniquely observed in our female unexplained infertility cohort represent putative genetic biomarkers that may predict a range of infertility conditions difficult to diagnose with existing clinical data. ObjectiveCopy number variants (CNVs) are genomic aberrations that alter the number of copies of genomic segments and therefore have the potential to alter dosage-sensitive genes and/or functional elements. Recent studies have shown that CNVs underlie various complex spectrum disorders and that the severity of the disorder is correlated with overall CNV burden. To investigate the role of CNVs in female infertility spectrum disorders, we have performed a survey examining CNVs in a cohort of patients with unexplained infertility. Copy number variants (CNVs) are genomic aberrations that alter the number of copies of genomic segments and therefore have the potential to alter dosage-sensitive genes and/or functional elements. Recent studies have shown that CNVs underlie various complex spectrum disorders and that the severity of the disorder is correlated with overall CNV burden. To investigate the role of CNVs in female infertility spectrum disorders, we have performed a survey examining CNVs in a cohort of patients with unexplained infertility. DesignRetrospective cohort of female patients with unexplained infertility. Retrospective cohort of female patients with unexplained infertility. Materials and MethodsGenomic DNA extracted from blood samples was obtained from patients undergoing non-donor in-vitro fertilization (IVF) cycles at a large academic medical center. CNVs were detected using a custom NimbleGen Comparative Genomic Hybridization (CGH) Whole-Genome Tiling Array optimized for fertility-related loci. The resulting log2 ratios of the raw intensities were then normalized and segmented. The prevalence of CNVs among the infertile cohort was compared to the Children's Hospital of Philadelphia (CHOP) CNV database of healthy individuals. Genomic DNA extracted from blood samples was obtained from patients undergoing non-donor in-vitro fertilization (IVF) cycles at a large academic medical center. CNVs were detected using a custom NimbleGen Comparative Genomic Hybridization (CGH) Whole-Genome Tiling Array optimized for fertility-related loci. The resulting log2 ratios of the raw intensities were then normalized and segmented. The prevalence of CNVs among the infertile cohort was compared to the Children's Hospital of Philadelphia (CHOP) CNV database of healthy individuals. ResultsApproximately 30% of the >3000 CNVs detected were unique to the infertile patients (P<10-7, Binomial Test of Proportions). Moreover, CNVs specific to the infertile cohort appear to be overrepresented among regions of the genome predicted to play a role in mammalian fertility (P<10-16, t-test). Approximately 30% of the >3000 CNVs detected were unique to the infertile patients (P<10-7, Binomial Test of Proportions). Moreover, CNVs specific to the infertile cohort appear to be overrepresented among regions of the genome predicted to play a role in mammalian fertility (P<10-16, t-test). ConclusionThe set of CNVs uniquely observed in our female unexplained infertility cohort represent putative genetic biomarkers that may predict a range of infertility conditions difficult to diagnose with existing clinical data. The set of CNVs uniquely observed in our female unexplained infertility cohort represent putative genetic biomarkers that may predict a range of infertility conditions difficult to diagnose with existing clinical data.

Targeted resequencing sheds light on the etiology of unexplained female infertilty

Approximately 15% of couples experiencing difficulty conceiving are diagnosed with idiopathic infertility. Genetic polymorphisms could shed light on many of these currently unexplained cases by revealing disruptions to oocyte quality or uterine receptivity that may exist on a subcellular level. To assess the role of single nucleotide variants (SNVs) in female infertility, we conducted an investigation surveying over 200 genomic loci predicted to be associated with female infertility among a cohort of patients with unexplained infertility. Retrospective cohort of female patients with unexplained infertility. Genomic DNA extracted from blood samples was obtained from 32 patients undergoing non-donor in-vitro fertilization (IVF) cycles at a large academic medical center. Based on literature review, ∼200 loci (spanning 250Mb) relating to female fertility were selected. Selected loci were targeted using a custom NimbleGen Sequence Capture Array, followed by paired-end Illumina HiSeq 2000 sequencing. Principal component analysis was used to correct for population stratification. Samples from the 1000 Genomes Project were used as controls. Among sites with read depths ≥20×, a total of ∼80,000 SNVs were detected, representing 0.3% of targeted sites. Removing singletons, this fraction was reduced to 0.2%. ∼500 SNVs are predicted to affect protein function. In comparison to the 1000 Genomes Project, ∼150 of these SNVs appear to be unique to the unexplained infertility cohort (P<.001, Logistic regression adjusted for population structure). Our preliminary survey of genetic variation among patients diagnosed with unexplained infertility revealed a number of potential genetic biomarkers associated with infertility. Based on these promising results, we are currently investigating female infertility-associated genetic variation through whole genome sequence analysis and in a larger validation cohort.

Fertility drugs and endometrial cancer risk: results from an extended follow-up of a large infertility cohort

Do fertility drugs influence the subsequent risk of endometrial cancer in a manner that is independent of other risk predictors, such as parity? In this follow-up of a large cohort of women evaluated for infertility and for whom information was captured on fertility drugs, indications for usage and other risk factors that might influence cancer risk, we found no evidence for a substantial relationship between fertility drug use and endometrial cancer risk. Although the hormonal etiology of endometrial cancer has been well established, it remains unclear whether the use of fertility drugs has an influence on risk. Results regarding the effects of fertility drugs on endometrial cancer risk have been inconsistent, although several studies have shown some evidence for possible increases in risk. The relationship is of particular interest given that clomiphene, a commonly prescribed drug, is a selective estrogen receptor modulator, with chemical properties similar to tamoxifen, another drug linked to an increase in endometrial cancer risk. In a retrospective cohort of 12 193 women evaluated for infertility between 1965 and 1988 at five US sites, follow-up was pursued through 2010 via both passive as well as active (questionnaire) means. Among the 9832 subjects for whom follow-up was allowed and achieved, 259 346 at-risk person-years (i.e. prior to hysterectomy) were accrued, and 118 invasive endometrial cancers identified. Cox regression determined hazard ratios (HRs) and 95% confidence intervals (CIs) for fertility treatments adjusted for endometrial cancer risk factors and causes of infertility. Although we observed slight increases in endometrial cancer risk associated with clomiphene (HR = 1.39, 95% CI: 0.96-2.01) and the less commonly prescribed gonadotrophins (1.34, 0.76-2.37), there were no convincing relationships of risk with either cycles of use or cumulative exposures for either drug. A statistically significant risk associated with the use of clomiphene among women who began use at younger ages (<30) (1.93, 1.24-3.00) may have reflected indications for drug usage rather than the effect of the drug itself. Women who received clomiphene followed by gonadotrophins were at a non-significantly elevated risk (1.77, 0.98-3.19). Like most studies of endometrial cancer, we were limited by sample sizes, particularly for evaluating subgroup associations. We were also unable to follow all women and were not able to obtain complete risk factor information (including hysterectomy status) for the entire cohort. Although we found no support for a relationship between fertility drugs and endometrial cancer risk, the association should continue to be monitored given that our study population was still young and had not yet reached the age of peak endometrial cancer incidence. This project was supported in part by funds from the intramural research program of the National Cancer Institute, National Institutes of Health. None of the authors has any conflicting interests to declare.

Proof of concept: A bioinformatic and serological screening method for identifying new peptide antigens for Chlamydia trachomatis related sequelae in women

This study aimed to identify new peptide antigens from Chlamydia (C.) trachomatis in a proof of concept approach which could be used to develop an epitope-based serological diagnostic for C. trachomatis related infertility in women. A bioinformatics analysis was conducted examining several immunodominant proteins from C. trachomatis to identify predicted immunoglobulin epitopes unique to C. trachomatis. A peptide array of these epitopes was screened against participant sera. The participants (all female) were categorized into the following cohorts based on their infection and gynecological history; acute (single treated infection with C. trachomatis), multiple (more than one C. trachomatis infection, all treated), sequelae (PID or tubal infertility with a history of C. trachomatis infection), and infertile (no history of C. trachomatis infection and no detected tubal damage). The bioinformatics strategy identified several promising epitopes. Participants who reacted positively in the peptide 11 ELISA were found to have an increased likelihood of being in the sequelae cohort compared to the infertile cohort with an odds ratio of 16.3 (95% c.i. 1.65–160), with 95% specificity and 46% sensitivity (0.19–0.74). The peptide 11 ELISA has the potential to be further developed as a screening tool for use during the early IVF work up and provides proof of concept that there may be further peptide antigens which could be identified using bioinformatics and screening approaches.

Psychiatric disorders in women with fertility problems: results from a large Danish register-based cohort study

Do women who don't succeed in giving birth after an infertility evaluation have a higher risk of psychiatric disorders compared with women who do? The results indicated that being unsuccessful in giving birth after an infertility evaluation could be an important risk factor for psychiatric disorders. Several studies have investigated the association between fertility treatment and psychological distress, but the results from these studies show substantial variation and lack of homogeneity that may be due to methodological limitations. A retrospective cohort study was designed using data from a cohort of 98 320 Danish women evaluated for fertility problems during 1973-2008 and linked to several Danish population-based registries. All women were followed from the date of first infertility evaluation until date of hospitalization for the psychiatric disorder in question, date of emigration, date of death or 31 December 2008, whichever occurred first. Owing to the precise linkage between the infertility cohort and the Danish population-based registries, using the unique Danish personal identification number, virtually no women were lost to follow-up. Information on reproductive status for all women in the infertility cohort was obtained by linkage to the Danish Medical Birth Registry. A total of 53 547 (54.5%) women gave birth after the initial infertility evaluation, whereas 44 773 (45.5%) women did not gave birth after the evaluation. To determine psychiatric disorders diagnosed in the women after enrolment in the infertility cohort, the cohort was linked to the Danish Psychiatric Central Registry. A total of 4633 women were hospitalized for a psychiatric disorder. The Cox proportional hazard regression model was applied to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the association between parity status after the initial infertility evaluation and risk of hospitalization for various groups of psychiatric disorders, including 'all mental disorders' and six main discharge subgroups labelled: 'alcohol and intoxicant abuse', 'schizophrenia and psychoses', 'affective disorders', 'anxiety, adjustment and obsessive compulsive disorders', 'eating disorder' and 'other mental disorders'. The incidence rate for all mental disorders was 393 cases per 100 000 person-years among women who did not succeed in giving birth after the infertility evaluation but only 353 cases per 100 000 person-years among women who succeeded in giving birth after the infertility evaluation. Women not giving birth after the infertility evaluation had an increased risk of hospitalization for all mental disorders (HR 1.17, 95% CI 1.11; 1.25), alcohol and intoxicant abuse (HR 2.02, 95% CI 1.69; 2.41), schizophrenia and psychoses (HR 1.46, 95% CI 1.17; 1.82) and other mental disorders (HR 1.42, 95% CI 1.27; 1.58) compared with women who gave birth after the infertility evaluation. In contrast, the risk of affective disorders (HR 0.90, 95% CI 0.81; 0.99) was decreased among women not giving birth after the infertility evaluation. Finally, the risk of anxiety, adjustment and obsessive compulsive disorders (HR 1.07, 95% CI 0.97; 1.17) as well as of eating disorders (HR 1.40, 95% CI 0.88; 2.22) was not significantly affected by parity status after the infertility evaluation. As only psychiatric conditions warranting hospitalization could be included in the present study, the true incidence of all psychiatric disorders among women with fertility problems is likely to be somewhat underestimated. Furthermore, since detailed information on fertility treatment was not available for all cohort members the association between different modalities of assisted reproductive techniques and risk of psychiatric disorders was not assessed. Clinicians and other healthcare personnel involved in diagnosis and treatment of women with fertility problems should be aware of the potential risk modification of psychiatric disorders associated with unsuccessful fertility treatment. Hence, our results may point to new aspects of follow-up of women with fertility problems who are unsuccessful in giving birth in order to prevent or identify and treat these possible psychological side effects. The study was supported by the Danish Cancer Society (award number: 96 222 54). All authors report no conflicts of interest.

The impact of social relations among men and women in fertility treatment on the decision to terminate treatment

Do social support and social strain from social relations have an impact on the decision to terminate fertility treatment among men and women after 1 year of unsuccessful treatment? Several functional aspects of social relations show an impact on the probability to terminate treatment; social support from family significantly decreases the probability to terminate and experience of conflicts or problematic communication with the partner significantly increases the probability to terminate treatment. Fertility patients can experience psychological, physical and economical strain as consequences of infertility and fertility treatment, and previous studies have shown that these pressures increase the probability of deciding to terminate treatment before the treatment options are exhausted. Some studies have indicated that social relations can also have an effect. This study is part of the prospective Infertility Cohort from the Copenhagen Multi-centre Psychosocial Infertility Research Programme. Baseline data were collected during January 2000-August 2001 among patients recruited at five Danish fertility clinics during their initial visit and follow-up data were collected after 1 year. The study group (n = 777; 427 women, 350 men) consisted of patients who did not achieve a live birth or an ongoing pregnancy during follow-up. Social support and strain from the patients' partner, family, family-in-law, friends and colleagues were measured at baseline and the decision to terminate treatment while treatment options were not yet exhausted was measured as the outcome at the 1-year follow-up. At the 1-year follow-up, 23% of the study group had decided to terminate treatment. For women, low levels of family support, specifically with regard to infertility, were associated with the termination of treatment after 1 year [odds ratio (OR) 6.1, 95% confidence interval (CI) 2.2-16.8] and, for men, low levels of general family support had a similar impact (OR 2.6, 95% CI 1.0-7.0). For men, difficulties in communicating with their partner about the infertility increased the probability of terminating the treatment (OR 2.3, 95% CI 1.2-4.1) and, for women, frequent conflicts with their partner increased the probability of terminating the treatment (OR 12.4, 95% CI 2.9-54.1). For women, conflicts with friends were also a predictor of treatment termination (OR 2.2, 95% CI 1.2-4.2). Functional aspects of social relations have an impact on the decision to terminate fertility treatment among men and women. The findings in this study provide new insights into how the close social environment can have implications for men and women going through fertility treatment. This study has received support from the Danish Health Insurance Fund (J.nr. 11/097-97), the Else and Mogens Wedell-Wedellsborgs Fund, the manager E. Danielsens and Wife's Fund, the merchant L.F. Foghts Fund, the Jacob Madsen and Wife Olga Madsen's Fund, and the Engineer K.A. Rohde and Wife's Fund. The authors have no conflicts of interest to declare.

Should TSPYL1 mutation screening be included in routine diagnostics of male idiopathic infertility?

To investigate a putative role of TSPYL1 in male idiopathic infertility. Clinical article. University hospital. A total of 104 infertile men were selected with idiopathic nonobstructive azoospermia, cryptozoospermia, oligozoospermia, oligonecrozoospermia, and oligoasthenoteratozoospermia (OAT) syndrome, along with a control group of 106 men with proven paternity. Mutation screening of the coding region and parts of the 5' and 3' untranslated regions of the TSPYL1 gene was performed by polymerase chain reaction and sequencing. Occurrence of TSPYL1 single-nucleotide polymorphisms (SNPs) and mutations. In these cohorts, eight known TSPYL1 SNPs were identified, none of which was significantly associated with male infertility. Two potentially disease-causing variants were detected in the infertile cohort: one man with azoospermia was found to be heterozygous for the novel TSPYL1 variant c.419C>G (p.Ser140Cys), and the rare substitution c.1098C>A (p.Phe366Leu) was identified in a man with OAT syndrome in the heterozygous state. Additionally, one fertile man was found to be heterozygous for the rare variant c.487G>A (p.Val163Ile). In silico analyses predicted a nonpathogenic effect for all amino acid exchanges, although protein features might be affected by p.Ser140Cys and p.Phe366Leu, respectively. Mutations in the TSPYL1 gene do not seem to play a major role in the pathogenesis of idiopathic male infertility, and mutation screening of the TSPYL1 gene can currently not be recommended in routine diagnostics of idiopathic male infertility.

Fecundity and sex ratio of offspring in an infertile cohort

To determine whether male and female subfecundity is associated with the gender ratio. Retrospective cohort study. Reproductive endocrinology clinics in California. A cohort of 30,448 women who sought infertility treatment or evaluation in California between 1990 and 1998 was identified. A fertile comparison group was assembled after matching data from vital statistics records. Not applicable. Multivariate logistic regression was used to determine the odds of a male birth based on fertility status. We identified 5,293 infertile women and 6,730 fertile matched women in the live-birth and fetal death records. There were 6,178 children born to women evaluated and/or treated for infertility, compared with 9,131 born to fertile women, for a total of 15,309 births. There was no significant difference in the secondary sex ratio between births in the infertile cohort and the fertile cohort or on the basis of male factor infertility versus female factor infertility. After controlling for confounding factors, there was no difference in sex ratio based on the use of advanced reproductive technologies, duration of infertility treatment, or the type of infertility. This study found no statistical evidence to support an association between infertility and secondary sex ratio.

2285 ATTITUDES TOWARDS ADOPTION AMONG MALES SEEKING FERTILITY TREATMENT

You have accessJournal of UrologyInfertility: Therapy1 Apr 20112285 ATTITUDES TOWARDS ADOPTION AMONG MALES SEEKING FERTILITY TREATMENT Kuwong Mwamukonda, James Smith, Susan Millstein, Robert Nachtigall, and Patricia Katz Kuwong MwamukondaKuwong Mwamukonda San Antonio, TX More articles by this author , James SmithJames Smith San Francisco, CA More articles by this author , Susan MillsteinSusan Millstein San Francisco, CA More articles by this author , Robert NachtigallRobert Nachtigall San Francisco, CA More articles by this author , and Patricia KatzPatricia Katz San Francisco, CA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2529AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Infertility affects approximately 15% of couples in the United States, with a male factor present in 40%. Significantly more men than women have adopted children in their lifetime, as more men than women adopt the prior children of their spouses, and male homosexual couples are primarily dependent upon adoption for parenthood. Despite this fact, most studies have evaluated adoption-related attitudes only among women. This study examined male attitudes towards adoption compared to female in the baseline evaluation of a prospective cohort of couples presenting for infertility treatment. METHODS The infertility cohort was comprised of men and women from eight community and academic reproductive endocrinology clinics. Attitudes regarding adoption were obtained from a series of questions included in the enrollment questionnaire. Responses were on a scale of 0–10 signifying “definitely would not” to “definitely would”. Demographic and socioeconomic characteristics were determined by self report. Fertility history and diagnosis were obtained from the medical record. RESULTS Adoption questions were completed by 762 participants. Mean male age was 36.9±5.5 years, with a female age of 35.7±4.8 years. Among this cohort, 74% were white, 70% college-educated, with a yearly income of <$100,000 in 65%. A male factor was identified in 37.8% of couples. Men were significantly less worried than women that the birthmother (BM) would want the child back (p<0.001). They were also 50% less likely to know someone who started to adopt a child before having the BM change her mind (RR 0.49, p<0.001). Men were less worried about the expense of adoption (p<0.001), the emotional stress of the process (p<0.001); less concerned about adoption causing others to be aware of their infertility (p<0.001), to make judgments about their parenting (p=0.009), or to have a claim to their child (p<0.001). Men were more likely than women to believe that adoption would result in them becoming parents (p=0.04). CONCLUSIONS Men's perspectives on adoption differ significantly from women's across a wide range of attitudes towards adoption. These data will help inform physicians involved in counseling infertile males regarding their treatment options. As men were generally more accepting of adoption, specific information describing adoption-related services could be provided at an earlier stage in the treatment process. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e916 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kuwong Mwamukonda San Antonio, TX More articles by this author James Smith San Francisco, CA More articles by this author Susan Millstein San Francisco, CA More articles by this author Robert Nachtigall San Francisco, CA More articles by this author Patricia Katz San Francisco, CA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

A rare synaptonemal complex protein 3 gene variant in unexplained female infertility

Synaptonemal complex protein 3 (SYCP3) plays a critical role in homologous chromosome pairing and recombination in meiosis, and mice deficient in this gene show infertility in males and subfertility in females. The aim of our current study was to determine whether genetic alterations in the SYCP3 gene are associated with female infertility in humans. We examined sequence variations of the SYCP3 gene in genomic DNA from 88 Japanese women with unexplained infertility and 165 samples obtained from a fertile control group. Case-control study using seven tagging single nucleotide polymorphisms revealed no significant association between common SYCP3 variants and unexplained infertility. However, only infertile women were homozygous for the minor allele of a novel rare variant in the coding region, c.666A>G (222Q>Q). The minor allele frequency was significantly higher in the infertile cohort (P< 0.05). This variant is predicted to create a cryptic splice site, although the expression of a mini-gene harboring the variant in HeLa cells or mouse testis did not demonstrate any effects on gene splicing. Our current findings therefore suggest that the c.666A>G variant in the SYCP3 gene might possibly contribute to female infertility in humans, although larger studies are needed to assess the possible effects of SYCP3 gene variation on human female infertility.

Time costs of fertility care: the hidden hardship of building a family

OBJECTIVE: To determine the time costs of seeking and utilizing fertility care among infertile couples.DESIGN: Prospective cohort.MATERIALS AND METHODS: Fertility outcomes and key demographic and medical data were determined through interviews and medical record abstraction. The infertility cohort was assembled from 8 community and academic reproductive endocrinology clinics. Interviews were conducted at enrollment, and at 4, 10, and 18 months. Monthly cost diaries were completed by study participants. Participants recorded in their diaries time spent on provider visits, travel, telephone, and “other” (e.g. lab testing, support groups, internet research, picking up medications). Participants also recorded paid time off of work due to the effects or side effects of fertility tests or treatment, or to being upset or distressed about their fertility problems or experiences.RESULTS: Diaries were completed by 361 subjects. The mean time spent on visits, travel, telephone, and “other” was 153 hours (Range 0-203). Assuming an 8 hour work day, an average of 19.1 days was spent on these activities. The greatest amount of time was spent on provider visits (mean 62.5 hours), “other” (mean 39.3 hours), travel (mean 38.6 hours), and phone calls (mean 12.3 hours). The total time expenditure was significantly greater for IVF (176.5 hours) compared to IUI (148.0 hours) and no cycle-based treatment (102.5 hours). The mean paid time off of work for at least one member of the couple due to fertility treatment or treatment-related distress was 16.6 days and 6.6 days, respectively.CONCLUSION: Over the course of an 18-month period, couples pursuing fertility treatment devoted nearly 3 work-weeks to fertility diagnostic evaluations, provider visits, and other fertility related activities. The time spent pursuing fertility care and time off work adds to the already significant financial and emotional burdens of fertility treatment. OBJECTIVE: To determine the time costs of seeking and utilizing fertility care among infertile couples. DESIGN: Prospective cohort. MATERIALS AND METHODS: Fertility outcomes and key demographic and medical data were determined through interviews and medical record abstraction. The infertility cohort was assembled from 8 community and academic reproductive endocrinology clinics. Interviews were conducted at enrollment, and at 4, 10, and 18 months. Monthly cost diaries were completed by study participants. Participants recorded in their diaries time spent on provider visits, travel, telephone, and “other” (e.g. lab testing, support groups, internet research, picking up medications). Participants also recorded paid time off of work due to the effects or side effects of fertility tests or treatment, or to being upset or distressed about their fertility problems or experiences. RESULTS: Diaries were completed by 361 subjects. The mean time spent on visits, travel, telephone, and “other” was 153 hours (Range 0-203). Assuming an 8 hour work day, an average of 19.1 days was spent on these activities. The greatest amount of time was spent on provider visits (mean 62.5 hours), “other” (mean 39.3 hours), travel (mean 38.6 hours), and phone calls (mean 12.3 hours). The total time expenditure was significantly greater for IVF (176.5 hours) compared to IUI (148.0 hours) and no cycle-based treatment (102.5 hours). The mean paid time off of work for at least one member of the couple due to fertility treatment or treatment-related distress was 16.6 days and 6.6 days, respectively. CONCLUSION: Over the course of an 18-month period, couples pursuing fertility treatment devoted nearly 3 work-weeks to fertility diagnostic evaluations, provider visits, and other fertility related activities. The time spent pursuing fertility care and time off work adds to the already significant financial and emotional burdens of fertility treatment.

Disclosure patterns of mode of conception among mothers and fathers-5-year follow-up of the Copenhagen Multi-centre Psychosocial Infertility (COMPI) cohort

Most studies on disclosure of mode of conception after fertility treatment have focused on donor insemination. We present a large, longitudinal cohort study of fertility patients who conceived through a variety of fertility treatments, including both non-donor and donor techniques. A cohort of 2812 women and men (n = 1406 couples) received questionnaires when initiating fertility treatment and at 1-year and 5-year follow-ups. At the 5-year follow up, the response rate was 69.4% and 1036 of the responding participants had at least one child born after fertility treatment. Around 66% of the children were conceived with in vitro fertilization or intrauterine insemination with partners semen, 26% with intracytoplasmic sperm injection, 7% with donor gametes and <1% with other treatments. The parents were asked whether they already had or intended to disclose the conception method to the child and to others. We used logistic regression to identify determinants among women and men for disclosure. Most of the parents had disclosed or intended to disclose the mode of conception to the child, and almost everyone had disclosed to someone else. Not having used donor gametes was a significant determinant of disclosure both to the child and to other people among women and men. Having disclosed to other people was a significant predictor for having disclosed or intending to disclose to the child. Among women, low social class was a significant determinant of disclosure to the child. Among men, satisfaction with the medical treatment was a significant determinant of disclosure to other people. We found a large majority who had or intended to disclose to the child how he/she was conceived. Non-disclosure was significantly related to the use of donor gametes.