Search

According to existing studies, sedentary behavior contributes to male infertility. Both preclinical and clinical studies have investigated the association between physical exercise, semen quality, and pregnancy rates with heterogeneous results. The current review sought to examine the relationship between physical activity (PA) and male infertility, semen characteristics, and pregnancy rates. Pre-clinical studies demonstrated mixed benefits from exercise, with diet being an important consideration. Some forms of PA showed an improvement in pregnancy rates, while others did not consistently improve semen quality. Data also suggests that more intense exercise and certain types of exercise may impair male fertility. Given the limited number of randomized trials, future research is required to examine the relationship between specific forms of exercise and semen parameters along with reproductive outcomes. [ABSTRACT FROM AUTHOR]

Purpose: In industrialized countries, air pollutants levels have been monitored closely for environmental and research issues. Using Italian data, we aimed to investigate the association between air pollutants levels and semen parameters in a cohort of non-Finnish white-European men presenting for couple’s infertility. Materials and Methods: Complete demographic and laboratory data from 1,152 infertile men consecutively assessed between January 2015 and January 2018 were analyzed. Semen analyses were based on the 2010 World Health Organization reference criteria. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). We analyzed the annual average level of the three main markers of air pollution (Pm10, Pm2.5, and NO2) between 2014 and 2018. Descriptive statistics, linear and logistic regression analyses tested the association between air pollutants levels and semen parameters. Results: Of 1,152 men, 87 (7.55%) had normal sperm parameters at first semen analysis. Of 1,065 patients with abnormal semen analyses, 237 (22.25%), 324 (30.42%), and 287 (26.95%) patients presented 1, 2 or 3 abnormalities, respectively, and 217 (20.38%) were azoospermic. At linear regression analysis, Pm10, Pm2.5, and NO2 were negatively associated with sperm morphology (Pm10: β=-0.5288 µg/m³, p=0.001; Pm2.5: β=-0.5240 µg/m³, p=0.019; NO2: β=-0.4396 µg/m3, p<0.0001). Furthermore, the adjusted odds of normal sperm morphology <4% were 1.06 (95% confidence interval [CI], 1.03–1.09; p=0.007) for Pm10, 1.07 (95% CI, 1.03–1.11; p=0.007) for Pm 2.5, and 1.03 (95% CI, 1.02–1.05; p=0.001) for NO2, respectively. Conclusions: In a large homogenous cohort of infertile men, Pm10, Pm 2.5, and NO2 levels were negatively associated with sperm morphology. Conversely, no clear association was observed with other macroscopic sperm parameters. [ABSTRACT FROM AUTHOR]

Study Question: Is there an association between fertility status, method of conception and the risks of birth defects and childhood cancer?Summary Answer: The risk of childhood cancer had two independent components: (i) method of conception and (ii) presence, type and number of birth defects.What Is Known Already: The rarity of the co-occurrence of birth defects, cancer and ART makes studying their association challenging. Prior studies have indicated that infertility and ART are associated with an increased risk of birth defects or cancer but have been limited by small sample size and inadequate statistical power, failure to adjust for or include plurality, differences in definitions and/or methods of ascertainment, lack of information on ART treatment parameters or study periods spanning decades resulting in a substantial historical bias as ART techniques have improved.Study Design, Size, Duration: This was a population-based cohort study linking ART cycles reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) from 1 January 2004 to 31 December 2017 that resulted in live births in 2004-2018 in Massachusetts and North Carolina and live births in 2004-2017 in Texas and New York. A 10:1 sample of non-ART births were chosen within the same time period as the ART birth. Non-ART siblings were identified through the ART mother's information. Children from non-ART births were classified as being born to women who conceived with ovulation induction or IUI (OI/IUI) when there was an indication of infertility treatment on the birth certificate, and the woman did not link to the SART CORS; all others were classified as being naturally conceived.Participants/materials, Setting, Methods: The study population included 165 125 ART children, 31 524 non-ART siblings, 12 451 children born to OI/IUI-treated women and 1 353 440 naturally conceived children. All study children were linked to their respective State birth defect registries to identify major defects diagnosed within the first year of life. We classified children with major defects as either chromosomal (i.e. presence of a chromosomal defect with or without any other major defect) or nonchromosomal (i.e. presence of a major defect but having no chromosomal defect), or all major defects (chromosomal and nonchromosomal), and calculated rates per 1000 children. Logistic regression models were used to generate adjusted odds ratios (AORs) and 95% CIs of the risk of birth defects by conception group (OI/IUI, non-ART sibling and ART by oocyte source and embryo state) with naturally conceived children as the reference, adjusted for paternal and maternal ages; maternal race and ethnicity, education, BMI, parity, diabetes, hypertension; and for plurality, infant sex and State and year of birth. All study children were also linked to their respective State cancer registries. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs of cancer by birth defect status (including presence of a defect, type and number of defects), and conception group.Main Results and the Role Of Chance: A total of 29 571 singleton children (2.0%) and 3753 twin children (3.5%) had a major birth defect (chromosomal or nonchromosomal). Children conceived with ART from autologous oocytes had increased risks for nonchromosomal defects, including blastogenesis, cardiovascular, gastrointestinal and, for males only, genitourinary defects, with AORs ranging from 1.22 to 1.85; children in the autologous-fresh group also had increased risks for musculoskeletal (AOR 1.28, 95% CI 1.13, 1.45) and orofacial defects (AOR 1.40, 95% CI 1.17, 1.68). Within the donor oocyte group, the children conceived from fresh embryos did not have increased risks in any birth defect category, whereas children conceived from thawed embryos had increased risks for nonchromosomal defects (AOR 1.20, 95% CI 1.03, 1.40) and blastogenesis defects (AOR 1.74, 95% CI 1.14, 2.65). The risk of cancer was increased among ART children in the autologous-fresh group (HR 1.31, 95% CI 1.08, 1.59) and non-ART siblings (1.34, 95% CI 1.02, 1.76). The risk of leukemia was increased among children in the OI/IUI group (HR 2.15, 95% CI 1.04, 4.47) and non-ART siblings (HR 1.63, 95% CI 1.02, 2.61). The risk of central nervous system tumors was increased among ART children in the autologous-fresh group (HR 1.68, 95% CI 1.14, 2.48), donor-fresh group (HR 2.57, 95% CI 1.04, 6.32) and non-ART siblings (HR 1.84, 95% CI 1.12, 3.03). ART children in the autologous-fresh group were also at increased risk for solid tumors (HR 1.39, 95% CI 1.09, 1.77). A total of 127 children had both major birth defects and cancer, of which 53 children (42%) had leukemia. The risk of cancer had two independent components: (i) method of conception (described above) and (ii) presence, type and number of birth defects. The presence of nonchromosomal defects increased the cancer risk, greater for two or more defects versus one defect, for all cancers and each type evaluated. The presence of chromosomal defects was strongly associated with cancer risk (HR 8.70 for all cancers and HR 21.90 for leukemia), further elevated in the presence of both chromosomal and nonchromosomal defects (HR 21.29 for all cancers, HR 64.83 for leukemia and HR 4.71 for embryonal tumors). Among the 83 946 children born from ART in the USA in 2019 compared to their naturally conceived counterparts, these risks translate into an estimated excess of 761 children with major birth defects, 31 children with cancer and 11 children with both major birth defects and cancer.Limitations, Reasons For Caution: In the SART CORS database, it was not possible to differentiate method of embryo freezing (slow freezing versus vitrification), and data on ICSI were only available in the fresh embryo ART group. In the OI/IUI group, it was not possible to differentiate type of non-ART treatment utilized, and in both the ART and OI/IUI groups, data were unavailable on duration of infertility. Since OI/IUI is underreported on the birth certificate, some OI/IUI children were likely included among the naturally conceived children, which will decrease the difference between all the groups and the naturally conceived children.Wider Implications Of the Findings: The use of ART is associated with increased risks of major nonchromosomal birth defects. The presence of birth defects is associated with greater risks for cancer, which adds to the baseline risk in the ART group. Although this study does not show causality, these findings indicate that children conceived with ART, non-ART siblings, and all children with birth defects should be monitored more closely for the subsequent development of cancer.Study Funding/competing Interest(s): This project was supported by grant R01 HD084377 from the National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Child Health and Human Development, or the National Institutes of Health, nor any of the State Departments of Health which contributed data. M.L.E. reports consultancy for Ro, Hannah, Dadi, Sandstone and Underdog; presidency of SSMR; and SMRU board member. The remaining authors report no conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Purpose: Inactivating mutations in mitochondrial aldehyde dehydrogenase 2 (ALDH2) are highly prevalent. The most common variant allele, ALDH2*2, is present in 40%e50% of East Asians, and causes acetaldehyde accumulation, flushing and tachycardia after alcohol intake. The relationship between alcohol intake and ALDH2 genotype on semen parameters remains unknown. Materials and Methods: We conducted a cross-sectional study to determine the association between ALDH2 genotype, alcohol consumption and semen parameters among East Asian men. Volunteers completed a survey and submitted a semen sample for analysis. Participants were genotyped to determine ALDH2 status (ALDH2*1/*1, ALDH2*1/*2, ALDH2*2/*2), and immunohistochemical staining was used to determine protein expression of ALDH2 in spermatozoa. Results: Of 112 men 45 (40.2%) were ALDH2*2 carriers. Among ALDH2*2 carriers, alcohol consumption was associated with significantly lower total sperm motility (median 20% [interquartile range 11%e42%] vs 43% [IQR 31%e57%], p[0.005) and progressive sperm motility (19% [IQR 11%e37%] vs 36% [IQR 25%e53%], p[0.008). Among alcohol consumers, ALDH2*2 carriers had significantly lower total sperm motility (20% [IQR 11%ee42%] vs 41% [IQR 19%e57%], p[0.02), progressive sperm motility (19% [IQR 11%e37%] vs 37% [IQR 17%e50%], p[0.02) and total motile sperm count (28 million [M; IQR 9e79M] vs 71M [IQR 23e150M], p[0.05) compared to ALDH2*1/*1 individuals. Secondly, ALDH2 expression in human spermatozoa was significantly lower in ALDH2*2 carriers (ALDH2*1/*1 vs ALDH2*1/*2, p[0.01; ALDH2*1/*1 vs ALDH2*2/*2, p <0.001). Conclusions: Our findings suggest genotyping ALDH2, coupled with alcohol cessation counseling, may improve semen parameters among men. [ABSTRACT FROM AUTHOR]

Study Question: What is the load, distribution and added clinical value of secondary findings (SFs) identified in exome sequencing (ES) of patients with non-obstructive azoospermia (NOA)?Summary Answer: One in 28 NOA cases carried an identifiable, medically actionable SF.What Is Known Already: In addition to molecular diagnostics, ES allows assessment of clinically actionable disease-related gene variants that are not connected to the patient's primary diagnosis, but the knowledge of which may allow the prevention, delay or amelioration of late-onset monogenic conditions. Data on SFs in specific clinical patient groups, including reproductive failure, are currently limited.Study Design, Size, Duration: The study group was a retrospective cohort of patients with NOA recruited in 10 clinics across six countries and formed in the framework of the international GEMINI (The GEnetics of Male INfertility Initiative) study.Participants/materials, Setting, Methods: ES data of 836 patients with NOA were exploited to analyze SFs in 85 genes recommended by the American College of Medical Genetics and Genomics (ACMG), Geisinger's MyCode, and Clinical Genome Resource. The identified 6374 exonic variants were annotated with ANNOVAR and filtered for allele frequency, retaining 1381 rare or novel missense and loss-of-function variants. After automatic assessment of pathogenicity with ClinVar and InterVar, 87 variants were manually curated. The final list of confident disease-causing SFs was communicated to the corresponding GEMINI centers. When patient consent had been given, available family health history and non-andrological medical data were retrospectively assessed.Main Results and the Role Of Chance: We found a 3.6% total frequency of SFs, 3.3% from the 59 ACMG SF v2.0 genes. One in 70 patients carried SFs in genes linked to familial cancer syndromes, whereas 1 in 60 cases was predisposed to congenital heart disease or other cardiovascular conditions. Retrospective assessment confirmed clinico-molecular diagnoses in several cases. Notably, 37% (11/30) of patients with SFs carried variants in genes linked to male infertility in mice, suggesting that some SFs may have a co-contributing role in spermatogenic impairment. Further studies are needed to determine whether these observations represent chance findings or the profile of SFs in NOA patients is indeed different from the general population.Limitations, Reasons For Caution: One limitation of our cohort was the low proportion of non-Caucasian ethnicities (9%). Additionally, as comprehensive clinical data were not available retrospectively for all men with SFs, we were not able to confirm a clinico-molecular diagnosis and assess the penetrance of the specific variants.Wider Implications Of the Findings: For the first time, this study analyzed medically actionable SFs in men with spermatogenic failure. With the evolving process to incorporate ES into routine andrology practice for molecular diagnostic purposes, additional assessment of SFs can inform about future significant health concerns for infertility patients. Timely detection of SFs and respective genetic counseling will broaden options for disease prevention and early treatment, as well as inform choices and opportunities regarding family planning. A notable fraction of SFs was detected in genes implicated in maintaining genome integrity, essential in both mitosis and meiosis. Thus, potential genetic pleiotropy may exist between certain adult-onset monogenic diseases and NOA.Study Funding/competing Interest(s): This work was supported by the Estonian Research Council grants IUT34-12 and PRG1021 (M.L. and M.P.); National Institutes of Health of the United States of America grant R01HD078641 (D.F.C., K.I.A. and P.N.S.); National Institutes of Health of the United States of America grant P50HD096723 (D.F.C. and P.N.S.); National Health and Medical Research Council of Australia grant APP1120356 (M.K.O'B., D.F.C. and K.I.A.); Fundação para a Ciência e a Tecnologia (FCT)/Ministério da Ciência, Tecnologia e Inovação grant POCI-01-0145-FEDER-007274 (A.M.L., F.C. and J.G.) and FCT: IF/01262/2014 (A.M.L.). J.G. was partially funded by FCT/Ministério da Ciência, Tecnologia e Ensino Superior (MCTES), through the Centre for Toxicogenomics and Human Health-ToxOmics (grants UID/BIM/00009/2016 and UIDB/00009/2020). M.L.E. is a consultant for, and holds stock in, Roman, Sandstone, Dadi, Hannah, Underdog and has received funding from NIH/NICHD. Co-authors L.K., K.L., L.N., K.I.A., P.N.S., J.G., F.C., D.M.-M., K.A., K.A.J., M.K.O'B., A.M.L., D.F.C., M.P. and M.L. declare no conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

There exist conflicting data in regard to the health outcomes of offspring born to infertile couples and follow up of offspring can be challenging. The objective of the study was to determine the association between infertility in men and women and the mental health of their offspring. The present study analyzes data obtained from the IBM Marketscan™ Commercial Claims and Encounters database from 2007 through 2015. Overall, 271,603 children of males with male factor infertility, 328,571 children of females with female factor infertility, 663,568 children of males who later underwent vasectomy were identified. The odds of psychosis were increased in offspring of those with male factor infertility (OR 1.25, 95% CI 1.22–1.29) and female factor infertility (OR 1.20, 95% CI 1.17–1.23). Offspring of infertile males (OR 1.19, 95% CI 1.13–1.26) and infertile females (OR 1.20, 95% CI 1.14–1.26) had an increased odds of autism compared to the reference group. In addition, offspring of infertile males (OR 1.48, 95% CI 1.28–1.7) and infertile females (OR 1.52, 95% CI 1.33–1.73) had higher odds of being diagnosed with an intellectual disability. Therefore, offspring of infertile men or women may have an increased risk of developing psychosis, autism, or intellectual disability. [ABSTRACT FROM AUTHOR]

Study Question: Has there been there a temporal change in time-to-pregnancy (TTP) in the USA.Summary Answer: Overall, TTP was stable over time, but a longer TTP for women over 30 and parous women was identified.What Is Known Already: Fertility rates in the USA have declined over the past several years. Although these trends have been attributed to changing reproductive intentions, it is unclear whether declining fecundity (the biologic ability to reproduce measured by TTP in the current report) may also play a role. Indeed, trends based on declining sperm quality and higher utilisation of infertility treatment suggest fecundity may be falling.Study Design, Size, Duration: This cross-sectional survey data from the National Survey of Family Growth was administered from 2002 to 2017. The surveys are based on nationally representative samples of reproductive-aged women in the USA. Interviews were conducted in person or through computer-assisted self-administration of sensitive questions.Participants/materials, Setting, Methods: The study included women who self-reported time spent trying to become pregnant allowing utilisation of the current duration approach to estimate the total duration of pregnancy attempt (i.e. TTP). In all, 1202 participants were analysed over each study period. To estimate a TTP distribution overall and by parity, we used a piecewise constant proportional hazards model that accounts for digit preference. Accelerated-failure-time regression models, which were weighted to account for the sampling design, were used to estimate time ratios (TRs). Models were adjusted for age, BMI, race, education, relationship status, parity, pelvic inflammatory disease treatment and any reproductive problems.Main Results and the Role Of Chance: Of the participants analysed, the average age was 31.8 and BMI was 28.6, which was similar across the survey periods. Relationship status was the only demographic characteristic that changed over time. All other variables remained constant across the study periods. Overall, TRs comparing TTP between 2002 and 2017 increased slightly (TR: 1.02, 95% CI: 0.99, 1.04). When stratified by parity, parous women had a longer TTP over the later years of the study (TR: 1.04, 95% CI: 1.01, 1.06). TTP remained constant for nulliparous women. Similarly, TTP also increased over time for women over age thirty (TR: 1.02, 1.00, 1.05) but not for women under age thirty.Limitations, Reasons For Caution: Small changes in data collection over time may have impacted the findings. We accounted for this in sensitivity analyses using imputed data. Overall, TRs were slightly attenuated using the imputed data, but represented similar patterns to the original data. Results for parous women and women over 30 remained consistent in the sensitivity analyses.Wider Implications Of the Findings: Consistent with reports of falling fertility rates and sperm counts, this study suggests parous and older couples in the USA may be taking longer to become pregnant. Although trends were suggestive of a small overall increase in TTP, particularly for parous women and women over age thirty, additional data are needed to attempt to understand these trends given the societal, economic and public health implications related to fecundity.Study Funding/competing Interest(s): Funding was provided by National Institutes of Health grant R03HD097287 to A.C.M. There are no competing interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: Male factor infertility (MFI) is a common medical condition which requires high‐quality research to guide clinical practice; however, systematic reviews (SRs) and meta‐analyses (MAs) often vary in quality, raising concerns regarding the validity of their results. We sought to perform an objective analysis of SRs and MAs in MFI treatment and management and to report on the quality of published literature. Methods: A comprehensive search in PubMed/MEDLINE and Embase was used to identify relevant publications. Primary search terms were male infertility, male sterility, and male subfertility. Two authors independently performed searches, screened citations for eligibility, extracted data for analysis, and graded methodological quality using the validated AMSTAR (A Measurement Tool to Assess Systematic Reviews) instrument, a validated tool used in the critical appraisal of SRs/MAs. Results: Of 27 publications met inclusion criteria and were included in the analysis. Mean AMSTAR score (± SD) among all publications was 7.4 (1.9) out of 11, reflecting "fair to good" quality. Non‐pharmacological medical treatment for MFI was the most commonly assessed intervention (n = 13, 48.1%). No publications met all AMSTAR criteria. While the number of SRs/MAs has increased over time (P = 0.037), the quality of publications has not significantly changed (P = 0.72). SRs/MAs of the Cochrane Library had higher AMSTAR score than non‐Cochrane SRs/MAs (8.5 vs 6.3, P = 0.002). Conclusions: The methodological quality of SRs/MAs should be assessed to ensure high‐quality evidence for clinical practice guidelines in MFI treatment and management. This review highlights a need for increased effort to publish high‐quality studies in MFI treatment and management. [ABSTRACT FROM AUTHOR]

Purpose: Ongoing evidence has suggested the role of male factor infertility as a potential predictor of mortality and general health status. The aim of the present review is to update the current knowledge base regarding the association between male factor infertility and general health through a critical review of the literature. Materials and Methods: A systematic review of the literature was carried out from inception to November 2019 in order to evaluate significant associations between male infertility and adverse health outcomes such as cardiovascular, oncologic, metabolic and autoimmune diseases as well as overall mortality. Results: In all, 27 studies met inclusion criteria and were critically examined. Five studies examined male infertility and cardiovascular disease risk, 11 examined oncologic risk (e.g., overall cancer risk, testis and prostate cancer), 8 examined aggregate chronic medical diseases and 5 infertility related to incidence of mortality, for a total of 599,807 men diagnosed with any male factor infertility covering a period from 1916 to 2016. Conclusions: A man's fertility and overall health appear to be interconnected. Therefore, a diagnosis of male infertility may allow a window into future comorbidity and/or mortality which may help guide clinical decisions and counseling. Several possible etiologies such as genetic, epigenetic, developmental, and lifestyle-based factors need to be further evaluated in order to establish the underlying mechanisms between male infertility and health. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to characterize the demographics, usage patterns and complication rates of clomiphene use in male patients. Materials and Methods: We retrospectively analyzed male patients from ages 20 to 55 years old who were prescribed clomiphene citrate from 2001 to 2014 using the Truven Health MarketScan, a US claims database. We collected data regarding associated medical diagnoses, diagnostic testing, duration of use, and reported side effects including thrombotic events, vision problems, gynecomastia, mental disorders, liver disease, nausea, or skin problems. Results: In total, 12,318 men took clomiphene and represented the primary study cohort, with a mean age of 37.8 years. The percentage of men prescribed clomiphene increased over the study period, as did the average age of clomiphene users. Associated diagnoses included male infertility (52.0%), testicular hypofunction (13.5%), erectile dysfunction (2.4%), and low libido (0.4%). Associated testing included semen analysis (43.7%), testosterone (23.5%), luteinizing hormone (19.3%), and follicle-stimulating hormone (21.1%) levels. The median time of clomiphene use was 3.6 months, with 63% of men stopping within 6 months. No increased risk of reported clomiphene side effects were apparent in men taking the medication. Conclusions: There is a rising prevalence of clomiphene usage without associated adverse side effects in the US. The variability in associated diagnoses, diagnostic testing, and duration of use suggest a need for greater awareness of the proper evaluation and treatment of the men who are prescribed clomiphene. [ABSTRACT FROM AUTHOR]

Study Question: What is the risk of death among men with oligospermia, unspecified male factor and azoospermia in the years following fertility treatment?Summary Answer: No significantly elevated risk was observed among men with oligospermia and unspecified male factor, while an increased risk was found among men with azoospermia.What Is Known Already: Previous studies have shown associations between male factor infertility and risk of death, but these studies have relied on internal reference groups and the risk of death according to type of male infertility is not well characterized.Study Design, Size, Duration: In this prospective record-linkage cohort study, we identified men who had undergone medically assisted reproduction (MAR) between 1994 and 2015. Data was linked to the Danish causes of death register and sociodemographic registers through personal identification numbers assigned to all Danish citizens at birth.Participants/materials, Setting, Methods: Men that had undergone MAR in Denmark (MAR Cohort; n = 64 563) were identified from the Danish IVF register, which includes data on whether infertility was due to male factor. For each man in the MAR cohort, five age-matched men who became fathers without fertility treatment were selected from the general population (non-MAR fathers; n = 322 108). Men that could not adequately be tracked in the Danish CPR register (n = 1259) and those that were censored prior to study entry (n = 993) were excluded, leaving a final population of 384 419 men. Risk of death was calculated by Cox regression analysis with age as an underlying timeline and adjustments for educational attainment, civil status and year of study entry. The risk of death was compared among men with and without male factor infertility identified from the IVF register (internal comparisons) as well as to the non-MAR fathers (external comparison).Main Results and the Role Of Chance: The risk of death between the MAR cohort (all men, regardless of infertility) and the non-MAR fathers was comparable [hazard ratio (HR), 1.07; 95% CI, 0.98-1.15]. When the MAR cohort was limited to infertile men, these men were at increased risk of death [HR, 1.27; 95% CI, 1.12-1.44]. However, when stratified by type of male factor infertility, men with azoospermia had the highest risk of death, which persisted when in both the internal [HR, 2.30; 95% CI, 1.54-3.41] and external comparison [HR, 3.32; 95% CI, 2.02-5.40]. No significantly elevated risk of death was observed among men with oligospermia [HR, 1.14; 95% CI, 0.87-1.50] and unspecified male factor [HR, 1.10; 95% CI, 0.75-1.61] compared with the non-MAR fathers. The same trends were observed for the internal comparison.Limitations, Reasons For Caution: Duration of the follow-up was limited and there is limited generalizability to infertile men who do not seek fertility treatment.Wider Implications Of the Findings: Using national health registers, we found an increased risk of death among azoospermic men while no increased risk was found among men with other types of infertility. For the azoospermic men, further insight into causal pathways is needed to identify options for monitoring and prevention.Study Funding/competing Interest(s): This study is part of the ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS. C.G.'s research stay at Stanford was funded by grants from the University of Copenhagen, Kong Christian den Tiendes Fond, Torben og Alice Frimodt Fond and Julie Von Müllen Fond. M.E. is an advisor for Sandstone and Dadi. All other authors declare no conflict of interests.Trial Registration Number: Not relevant. [ABSTRACT FROM AUTHOR]

Study Question: Is female infertility associated with higher risk of cancer?Summary Answer: Although absolute risks are low, infertility is associated with higher risk of cancer compared to a group of non-infertile women.What Is Known Already: Infertile women are at higher risk of hormone-sensitive cancers. Information on risk of non-gynecologic cancers is rare and conflicting, and the effect of pregnancy on these risk associations is known for only a minority of cancer types.Study Design, Size, Duration: Retrospective cohort analysis between 2003 and 2016 using an insurance claims database.Participants/materials, Setting, Methods: In all, 64 345 infertile women identified by infertility diagnosis, testing or treatment were compared to 3 128 345 non-infertile patients seeking routine gynecologic care. Women with prior diagnosis of cancer or within 6 months of index event were excluded. Main outcomes were development of any malignancy and individual cancers as identified by ICD-9/ICD-10 codes. Results were adjusted for age at index date, index year, nulliparity, race, smoking, obesity, number of visits per year and highest level of education.Main Results and the Role Of Chance: Infertile women had an overall higher risk of developing cancer compared to non-infertile women (2.0 versus 1.7%, adjusted hazard ratio (aHR) = 1.18; CI: 1.12-1.24). In addition, the risk of uterine cancer (0.10 versus 0.06%, aHR = 1.78; CI: 1.39-2.28), ovarian cancer (0.14 versus 0.09%, aHR 1.64; CI: 1.33-2.01), lung cancer (0.21 versus 0.21%, aHR = 1.38; CI: 1.01-1.88), thyroid cancer (0.21 versus 0.16%, aHR = 1.29; CI: 1.09-1.53), leukemia (0.10 versus 0.06%, aHR = 1.55; CI: 1.21-1.98) and liver and gallbladder cancer (0.05 versus 0.03%, aHR = 1.59; CI: 1.11-2.30) were higher in infertile women compared to non-infertile women. In a subgroup analysis of women in each cohort who became pregnant and had a delivery during enrollment, the risk of uterine and ovarian cancer were similar between infertile and non-infertile women. In a subgroup analysis excluding women with PCOS and endometriosis from both cohorts, the risk of uterine cancer was similar between infertile and non-infertile women.Limitations, Reasons For Caution: Absolute risk of cancer was low, average follow up for each individual was limited, and average age at index date was limited. Insurance databases have known limitations.Wider Implications Of the Findings: Using claims-based data, we report that infertile women may have a higher risk of certain cancers in the years after infertility evaluation; continued follow up should be considered after reproductive goals are achieved.Study Funding/competing Interest(s): None. [ABSTRACT FROM AUTHOR]

There is an emerging body of evidence suggesting that male infertility may be a harbinger of future health. Potential associations between infertility and health may arise from genetic, developmental, and lifestyle factors. Studies have explored possible links between male infertility and oncologic, cardiovascular, metabolic, and autoimmune diseases. Male infertility may also be a predictor of hospitalization and mortality. Additional research is required to elucidate the mechanisms by which male infertility affects overall health. [ABSTRACT FROM AUTHOR]

Objective: To study the relationship between semen quality and pregnancy loss in a cohort of couples attempting to conceive.Design: Observational prospective cohort.Setting: Not applicable.Patient(s): Three hundred and forty-four couples with a singleton pregnancy observed daily through 7 postconception weeks of gestation.Intervention(s): None.Main Outcome Measure(s): Association between semen quality and pregnancy loss.Result(s): Ninety-eight (28%) of the couples experienced a pregnancy loss after singleton pregnancy. No differences were observed in semen volume, sperm concentration, total sperm count, sperm viability, or sperm morphology (World Health Organization [WHO] and strict criteria) by couple's pregnancy loss status irrespective of whether they were analyzed continuously or as dichotomous variables per the WHO 5th edition semen criteria. A dichotomous DNA fragmentation measure of ≥30% was statistically significantly associated with pregnancy loss. No association was identified with other sperm morphometric or movement measures. Of the 70 couples who re-enrolled after a pregnancy loss, 14 experienced a second loss. Similar findings were identified when examining semen quality from couples with recurrent pregnancy loss.Conclusion(s): Although a few trends were identified (e.g., DNA fragmentation), general semen parameters seemed to have little relation with risk of pregnancy loss or recurrent pregnancy loss at the population level. However, given that 30% of pregnancies end in miscarriage and half the fetal genome is paternal in origin, the findings await corroboration. [ABSTRACT FROM AUTHOR]

As the age of paternity rises in the developed world, issues of chronic disease may affect prospective fathers. Given the high prevalence of hypertension, researchers have begun to explore the relationship between hypertensive disease and male fertility. The current literature suggests an association between hypertension and semen quality. The use of various antihypertensive medications has also been linked to impaired semen parameters, making it difficult to discern whether the association exists with hypertension or its treatment. Further investigation is warranted to determine whether the observed associations are causal. [ABSTRACT FROM AUTHOR]

Purpose Although testosterone replacement therapy use in the United States has increased dramatically in the last decade, to our knowledge trends in testosterone replacement therapy use among reproductive-age men have not been investigated. We assessed changes in testosterone replacement therapy use and practice patterns among 18 to 45-year-old American men from 2003 to 2013 and compared them to older men. Materials and Methods This is a retrospective, cross-sectional analysis of men 18 to 45 and 56 to 64 years old who were enrolled in the Truven Health MarketScan® Commercial Claims Databases throughout each given calendar year from 2003 to 2013, including 5,094,868 men in 2013. Trends in the yearly rates of testosterone replacement therapy use were calculated using Poisson regression. Among testosterone replacement therapy users, the Cochran-Armitage test was used to assess temporal trends in age, formulation type, semen analysis and serum testosterone level testing during the 12 months preceding the documented use of testosterone replacement therapy. Results Between 2003 and 2013, there was a fourfold increase in the rate of testosterone use among 18 to 45-year-old men from 29.2/10,000 person-years to 118.1/10,000 person-years (p <0.0001). Among testosterone replacement therapy users, topical gel formulations were initially most used. Injection use then doubled between 2009 and 2012 (23.5% and 46.2%, respectively) and surpassed topical gel use in 2013. In men 56 to 64 years old there was a statistically significant threefold increase in testosterone replacement therapy use (p <0.0001), which was significantly smaller than the fourfold increase in younger men (p <0.0001). Conclusions In 2003 to 2013, testosterone replacement therapy use increased fourfold in men 18 to 45 years old compared to threefold in older men. This younger age group should be a focus for future studies due to effects on fertility and unknown long-term sequelae. [ABSTRACT FROM AUTHOR]

As paternal age increases in the developed world, more attention has been given to the effects of age on male reproductive and sexual function. Although the biologic potential for reproductive continues for most of a man's life, changes in sperm production do occur. In addition, erectile function changes with age, caused by the same factors that lead to other vascular disease. [ABSTRACT FROM AUTHOR]

Study Question: What is the relationship between couple's health and fecundity in a preconception cohort?Summary Answer: Somatic health may impact fecundity in men and women as couples whose male partner had diabetes or whose female partner had two or more medical conditions had a longer time-to-pregnancy (TTP).What Is Already Known: The impact of somatic health on human fecundity is hypothesized given the reported declines in spermatogenesis and ovulation among individuals with certain medical comorbidities.Study Design, Size, Duration: A population-based prospective cohort study recruiting couples from 16 counties in Michigan and Texas (2005-2009) using sampling frameworks allowing for identification of couples planning pregnancy in the near future. Five hundred and one couples desiring pregnancy and discontinuing contraception were followed-up for 12 months or until a human chorionic gonadotropin pregnancy was detected.Participants/materials, Settings, Methods: In all, 33 (21.4%) female and 41 (26.6%) male partners had medical conditions at baseline.Main Results and the Role Of Chance: Couples' medical comorbidity was associated with pregnancy status. Diabetes in either partner was associated with diminished fecundity, as measured by a longer TTP. Specifically, fecundability odds ratios (FORs) were below 1, indicating a longer TTP, for male partners with diabetes (0.35, 95% confidence interval (CI): 0.14-0.86) even in adjusted models (0.35, 95% CI: 0.13-0.88). Female partners with diabetes had comparable reductions in FORs; however, the analyses did not reach statistical significance (0.26, 95% CI: 0.03-1.98). Female partners with two or more medical conditions had a significantly longer TTP compared with women with no health problems (0.36, 95% CI: 0.14-0.92). Importantly, the presence of medical conditions was not associated with sexual frequency. We cannot rule out residual confounding, Type 2 errors for less prevalent medical conditions, or chance findings in light of the multiple comparisons made in the analysis.Limitations, Reasons For Caution: The findings require cautious interpretation given that medical diagnoses are subject to possible reporting errors, although we are unaware of any potential biases that may have been introduced, as participants were unaware of how long it would take to become pregnant upon enrollment.Wider Implications Of the Findings: The current report suggests a relationship between male and female diabetes and fecundity, and possibly somatic health more globally. Moreover, while the mechanism is uncertain, if corroborated, our data suggest that early evaluation and treatment may be warranted for diabetics prior to attempting to conceive.Study Funding/competing Interests: Intramural research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Contract nos. #N01-HD-3-3355, N01-HD-3-3356 and N01-HD-3-3358). The authors have no conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

Objective: To study the association between paternal medical comorbidities and the outcomes of assisted reproductive technology (ART).Design: Retrospective cohort study.Setting: Academic reproductive medicine center.Patient(s): We analyzed fresh ART cycles uszing freshly ejaculated sperm from the male partner of couples undergoing ART cycles from 2004 until 2014. We recorded patient and partner demographic characteristics. The cohort was linked to hospital billing data to obtain information on selected male partners' comorbidities identified using ICD-9-CM codes.Intervention(s): None.Main Outcome Measure(s): Fertilization, clinical pregnancy, miscarriage, implantation, and live-birth rates as well as birth weights and gestational ages.Result(s): In all, we identified 2,690 men who underwent 5,037 fresh ART cycles. Twenty-seven percent of men had at least one medical diagnosis. Men with nervous system diseases had on average lower pregnancy rates (23% vs. 30%) and live-birth rates (15% vs. 23%) than men without nervous system diseases. Lower fertilization rates were also observed among men with respiratory diseases (61% vs. 64%) and musculoskeletal diseases (61% vs. 64%) relative to those without these diseases. In addition, men with diseases of the endocrine system had smaller children (2,970 vs. 3,210 g) than men without such diseases. Finally, men with mental disorders had children born at an earlier gestational age (36.5 vs. 38.0 weeks).Conclusion(s): The current report identified a possible relationship between a man's health history and IVF outcomes. As these are potentially modifiable factors, further research should determine whether treatment for men's health conditions may improve or impair IVF outcomes. [ABSTRACT FROM AUTHOR]

Objective: To determine the incidence of chronic medical conditions of men with infertility.Design: Retrospective cohort study.Setting: Not applicable.Patient(s): Subjects contained within the Truven Health MarketScan claims database from 2001 to 2009.Intervention(s): Not applicable.Main Outcome Measure(s): The development of chronic medical conditions including hypertension, diabetes, hyperlipidemia, renal disease, pulmonary disease, liver disease, depression, peripheral vascular disease, cerebrovascular disease, heart disease, injury, alcohol abuse, drug abuse, anxiety disorders, and bipolar disorder.Result(s): In all, 13,027 men diagnosed with male factor infertility were identified with an additional 23,860 receiving only fertility testing. The average age was 33.1 years for men diagnosed with infertility and 32.8 years for men receiving testing alone. After adjusting for confounding factors, men diagnosed with male factor infertility had a higher risk of developing diabetes (hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.10-1.53), ischemic heart disease (HR 1.48, 95% CI 1.19-1.84), alcohol abuse (HR 1.48, 95% CI 1.07-2.05), and drug abuse (1.67, 95% CI 1.06-2.63) compared with men who only received infertility testing. Similar patterns were identified when comparing those with male factor infertility to vasectomized men. The association between male factor infertility and later health outcomes were strongest for men with longer follow-up.Conclusion(s): In this cohort of patients in a national insurance database, men diagnosed with male factor infertility had a significantly higher risk of adverse health outcomes in the years after an infertility evaluation. These findings suggest the overall importance of men's reproductive health and warrant additional investigation to understand the association and identify interventions to improve outcomes for these patients. [ABSTRACT FROM AUTHOR]

This month's Views and Reviews provides an added perspective to the World Health Organization laboratory manual for the examination and processing of human semen, which was recently published in the 6th edition. The first artice provides a historical context of the prior editions of the World Health Organization manuals and modifications adopted over the years. The next piece then provides additional perspectives on the methodologies used for the performance of semen analysis. The third article then examines some of the new semen analytic technologies and enhancements that have become more common over the years. Finally, the last article proposed where male reproductive testing will head in the coming years with emerging research and technologies. [ABSTRACT FROM AUTHOR]

Objective To identify differences in demographic and socio-economic factors between men seeking infertility evaluation and those undergoing vasectomy, to address disparities in access to these services. Patients and Methods Data from Cycle 6 and Cycle 7 (2002 and 2006-2008) of the National Survey of Family Growth ( NSFG) were reviewed. The NSFG is a multistage probability survey designed to capture a nationally representative sample of households with men and women aged 15-45 years in the USA. The variables analysed included age, body mass index, self-reported health, alcohol use, race, religious affiliation, marital status, number of offspring, educational attainment, income level, insurance status and metropolitan home designation. Our primary outcome was the correlation of these demographic and socio-economic factors with evaluation for male infertility or vasectomy. Results Of the 11 067 men identified through the NSFG, 466 men (4.2%) sought infertility evaluation, representing 2 187 455 men nationally, and 326 (2.9%) underwent a vasectomy, representing 1 510 386 men nationally. Those seeking infertility evaluation were more likely to be younger and have fewer children ( P = 0.001, 0.001) and less likely to be currently married (78 vs 74%; P = 0.010) or ever married (89 vs 97%; P = 0.002). Men undergoing a vasectomy were more likely to be white (86 vs 70%; P = 0.001). Men seeking infertility evaluation were more likely to have a college or graduate degree compared with men undergoing a vasectomy (68 vs 64%; P = 0.015). There was no difference between the two groups for all other variables. Conclusion While differences in demographic characteristics such as age, offspring number and marital status were identified, measures of health, socio-economic status, religion and insurance were similar between men undergoing vasectomy and those seeking infertility services. These factors help characterize the utilization of male reproductive health services in the USA and may help address disparities in access to these services and improve public health strategies. [ABSTRACT FROM AUTHOR]

Purpose Aberrations in reproductive fitness may be a harbinger of medical diseases in men. Data suggest a higher risk of testicular cancer in infertile men. However, the relationship between infertility and other cancers remains uncertain. Materials and Methods We analyzed subjects from the Truven Health MarketScan® claims database from 2001 to 2009. Infertile men were identified through diagnosis and treatment codes. Comparison groups were created of men who underwent vasectomy and a control cohort of men who were not infertile and had not undergone vasectomy. The incidence of cancer was compared to national U.S. estimates. Infertile men were also compared to men who underwent vasectomy and the control cohort using a Cox regression model. Results A total of 76,083 infertile men were identified with an average age of 35.1 years. Overall 112,655 men who underwent vasectomy and 760,830 control men were assembled. Compared to age adjusted national averages, infertile, vasectomy and control subjects in the study cohorts had higher rates of all cancers and many individual cancers. In time to event analysis, infertile men had a higher risk of cancer than those who underwent vasectomy or controls. Infertile men had a higher risk of testis cancer, nonHodgkin lymphoma and all cancers than the vasectomy and control groups. Conclusions Consistent with prior reports, we identified an increased risk of testicular cancer in infertile men. The current data also suggest that infertile men are at an increased risk of all cancers in the years after infertility evaluation. Future research should focus on confirming these associations and elucidating pathways between infertility and cancer. [ABSTRACT FROM AUTHOR]

Male factor infertility is widely considered a harbinger for a man's general health. Failure of reproduction often accompanies other underlying processes, with growing evidence suggesting that a diagnosis of infertility increases the likelihood of developing future cardiac, metabolic, and oncologic diseases. The goal of this review is to provide a comprehensive overview of the research on male fertility as a marker for current and future health. A multidisciplinary approach is essential, and there is growing consensus that the male fertility evaluation offers an opportunity to better men's wellness beyond their immediate reproductive ambitions. [ABSTRACT FROM AUTHOR]

Study Question: What is the relationship between semen parameters and mortality in men evaluated for infertility?Summary Answer: Among men undergoing an infertility evaluation, those with abnormal semen parameters have a higher risk of death, suggesting a possible common etiology between infertility and mortality.What Is Known Already: Conflicting data exist that suggest either an inverse relationship or no relationship between semen quality and mortality.Study Design, Size, Duration: A study cohort was identified from two centers, each specializing in infertility care. In California, we identified men with data from 1994 to 2011 in the Stanford Reproductive Endocrinology and Infertility semen database. In Texas, we identified men with data from 1989 to 2009 contained in the andrology database at the Baylor College of Medicine Special Procedures Laboratory who were evaluated for infertility. Mortality was determined by data linkage to the National Death Index or Social Security Death Index. Comorbidity was estimated based on calculation of the Charlson Comorbidity Index or Centers for Medicare & Medicaid Services-Hierarchical Condition Categories Model.Participants/materials, Setting, Methods: In all, 11,935 men were evaluated for infertility from 1989 to 2011. During 92 104 person years of follow-up, 69 of 11,935 men died (0.58%). The mean age at infertility evaluation was 36.6 years with a mean follow-up of 7.7 years.Main Results and the Role Of Chance: Compared with the general population, men evaluated for infertility had a lower risk of death with 69 deaths observed compared with 176.7 expected (Standardized mortality rate 0.39, 95% CI 0.30-0.49). When stratified by semen parameters, however, men with impaired semen parameters (i.e. male factor infertility) had significantly higher mortality rates compared with men with normal parameters (i.e. no male factor infertility). Low semen volume, sperm concentration, sperm motility, total sperm count and total motile sperm count were all associated with higher risk of death. In contrast, abnormal sperm morphology was not associated with mortality. While adjusting for current health status attenuated the association between semen parameters and mortality, men with two or more abnormal semen parameters still had a 2.3-fold higher risk of death compared with men with normal semen (95% CI 1.12-4.65).Limitations, Reasons For Caution: Our cohort represents infertile men, which may limit generalizability. As comorbidity relied on administrative data, granular information on each man regarding infertility diagnosis and lifestyle factors was unavailable.Wider Implications Of the Findings: Men with impaired semen parameters have an increased mortality rate in the years following an infertility evaluation suggesting semen quality may provide a marker of health.Study Funding/competing Interest(s): This study is supported in part by P01HD36289 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development, National Institutes of Health (to D.J.L. and L.I.L.). The project was also partially supported by an NIH CTSA award number UL1 RR025744. None of the authors has any conflict of interest to declare. [ABSTRACT FROM AUTHOR]

Background: Fertility potential and reproductive fitness may reflect a man's future health, given that over one-third of the male human genome is involved in reproduction. We sought to determine if offspring number predicts cardiovascular death in the US men.Methods: Using data from the NIH-AARP Diet and Health Study, 137,903 men (aged 50-71) without prior cardiovascular disease were followed-up for an average of 10.2 years. International Classification of Diseases, ninth edition, codes were used to establish the cause of death, and multivariable Cox proportional hazards modeling was used to estimate the association between offspring number and cardiovascular death while accounting for sociodemographic and lifestyle characteristics.Results: Almost all (92%) participants had fathered at least one child and 50% had three or more offspring. A total of 3082 men died of cardiovascular causes during follow-up for an age-adjusted incidence rate of 2.70 per 1000 person-years. Compared with fathers, after adjusting for sociodemographic and lifestyle factors, childless men had a 17% [hazard ratio (HR): 1.17; 95% confidence interval (CI): 1.03-1.32] increased risk of death from cardiovascular disease contracted in the study period, and this elevated risk appeared to extend also to men with only one child. In comparison with fathers of five or more children, adjusted relative hazards for cardiovascular mortality of this sort were 1.06 (95% CI: 0.92-1.22) for four children, 1.02 (0.90-1.16) for three children, 1.02 (0.90-1.16) for two children, 1.11 (0.95-1.30) for one child and 1.21 (1.03-1.41) for no children.Conclusions: Married men who have no children have a higher risk of dying from cardiovascular disease contracted after the age of 50 than men with two or more children. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of income, education, and race on the use and outcomes of infertility care.Design: Prospective cohort.Setting: Eight community and academic infertility practices.Patient(s): Three hundred ninety-one women presenting for an infertility evaluation.Intervention(s): Face-to-face and telephone interviews and questionnaires.Main Outcome Measure(s): Use of infertility services and odds of pregnancy. Linear and logistic regression used to assess relationship between racial and socioeconomic characteristics, use of infertility services, and infertility outcomes.Result(s): After adjustment for age and demographic and fertility characteristics, college-educated couples (β = $5,786) and households earning $100,000-$150,000 (β = $6,465) and ≥$150,000 (β = $8,602) spent significantly more on infertility care than their non-college-educated, lower-income counterparts. Higher income and college-educated couples were much more likely to use more cycles of higher-intensity fertility treatment. The increased cost of infertility care was primarily explained by these differences in number and type of infertility treatment. Even after adjustment for these factors and total amount spent on fertility care, having a college degree was associated with persistently higher odds of achieving a pregnancy (OR = 1.9).Conclusion(s): Education and household income were independently associated with the amount of money spent on fertility care. This relationship was primarily explained by types and intensity of infertility treatments used. Having at least a college degree was independently associated with improved odds of pregnancy. [ABSTRACT FROM AUTHOR]

The association between varicoceles and male infertility has been known since the 1950s; however, the pathophysiology of the process remains uncertain. The primary proposed hypotheses involve hyperthermia, venous pressure, testicular blood flow, hormonal imbalance, toxic substances, and reactive oxygen species. It is difficult to identify a single or dominant factor, and it is likely that many of these factors contribute to the infertile phenotype seen in clinical practice. Moreover, patient lifestyle and genetic factors likely affect patient susceptibilities to the varicocele insult. While the current studies have weaknesses, they provide building blocks for futures studies into the pathophysiology of the varicocele. [ABSTRACT FROM AUTHOR]

BACKGROUND: Investigators have postulated that family size may be influenced by biologic fertility potential in addition to sociodemographic factors. The aim of the current study is to determine if a diagnosis of infertility is associated with family size in the USA. METHODS: We analyzed data from the male and female samples of the 2002 National Survey of Family Growth using multivariable logistic regression models to determine the relationship between infertility and family size while adjusting for sociodemographic and reproductive characteristics. RESULTS: In the survey, 4409 women and 1739 men met the inclusion criteria, of whom 10.2% and 9.7%, respectively, were classified as infertile, on the basis of having sought reproductive assistance. Infertile females had a 34% reduced odds of having an additional child compared with women who did not seek reproductive assistance. For each additional 6 months it took a woman to conceive her first child, the odds of having a larger family fell by 9% and the odds of having a second child were reduced by 11%. A diagnosis of male infertility reduced the odds of having a larger family more than a diagnosis of female infertility. CONCLUSIONS: A diagnosis of infertility, especially male factor, is associated with reduced odds of having a larger family, implicating a biologic role in the determination of family size in the USA. [ABSTRACT FROM AUTHOR]

Objective: To determine the views toward donor sperm and eggs of both men and women. The use of donor sperm or ova becomes an option for some infertile couples.Design: Prospective cohort of infertile couples.Setting: Eight California reproductive endocrinology practices.Patient(s): Infertile couples (n=377) were recruited after an initial infertility clinic visit.Main Outcome Measure(s): From questionnaires administered at recruitment, ratings concerning the impact of the use of donor gametes were assessed. Differences between men and women in attitudes toward donor gametes were compared with analysis of variance (ANOVA). Linear regression was used to identify independent predictors of attitudes toward gametes.Result(s): Women's attitudes toward donor sperm were significantly more negative than their attitudes toward donor eggs (5.1+/-1.4 vs. 4.7+/-1.6). Similarly, male donor gamete attitude scores were higher for donor sperm compared with donor eggs (4.9+/-1.6 vs. 4.1+/-1.6). Both men and women agreed that the use of donor sperm was more likely to have negative effects on their relationship and negative societal ramifications. Female donor gamete attitude scores were predicted by marital status, race, and education, whereas men's scores were independent of all measured factors.Conclusion(s): Both men and women view the use of donor sperm with more skepticism compared with the use of donor eggs, suggesting a unique underlying perception regarding the use of male donor gametes. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of complementary and alternative medicine (CAM) use among couples seeking fertility care and to identify the predictors of CAM use in this population.Design: Prospective cohort study.Setting: Eight community and academic infertility practices.Patient(s): A total of 428 couples presenting for an infertility evaluation.Intervention(s): Interviews and questionnaires.Main Outcome Measure(s): Prevalence of complementary and alternative medicine therapy.Result(s): After 18 months of observation, 29% of the couples had utilized a CAM modality for treatment of infertility; 22% had tried acupuncture, 17% herbal therapy, 5% a form of body work, and 1% meditation. An annual household income of > or = $200,000 (odds ratio 2.8, relative to couples earning <$100,000), not achieving a pregnancy (odds ratio 2.3), and a positive attitude toward CAM use at baseline were independently associated with CAM use.Conclusion(s): A substantial minority of infertile couples use CAM treatments. CAM was chosen most commonly by wealthier couples, those not achieving a pregnancy, and those with a baseline belief in the effectiveness of CAM treatments. [ABSTRACT FROM AUTHOR]

Purpose: Ejaculatory duct obstruction is a treatable cause of male infertility but the diagnosis can be difficult to make. Transrectal ultrasound is valuable but not specific for ejaculatory duct obstruction. Adjunctive procedures, such as chromotubation and seminal vesicle aspiration, are more sensitive but not definitive, especially for partial obstruction. We describe what is to our knowledge a new hydraulic test and report its ability to identify physical and functional ejaculatory duct obstruction. Materials and Methods: Two groups of men were studied, including patients with infertility or ejaculatory pain in whom ejaculatory duct obstruction was suspected and fertile men undergoing vasectomy reversal (controls). In each cohort ejaculatory duct injection and manometry were performed. Patients with ejaculatory duct obstruction underwent transurethral ejaculatory duct resection based on routine criteria. Pressure was reassessed after resection. Manometry pressures were compared between controls and patients with ejaculatory duct obstruction, and correlated with the response to transurethral ejaculatory duct resection. Results: In the 7 controls (14 sides) mean ejaculatory duct opening pressure was 33.2 cm H2O. In the 9 patients (17 sides) with suspected ejaculatory duct obstruction mean ejaculatory duct opening pressure before transurethral ejaculatory duct resection was 116 cm H2O. In the 6 patients who underwent resection, which was unilateral and bilateral in 3 each, mean ejaculatory duct opening pressure decreased from 118 to 53 cm H2O. Of the 5 patients who underwent semen analyses before and after resection 80% showed an increase in ejaculate volume and/or at least 100% improvement in TMC (volume × concentration × motile fraction). Conclusions: Ejaculatory duct manometry with baseline values defined in fertile men demonstrates that men with clinically suspected ejaculatory duct obstruction have higher ejaculatory duct opening pressure than fertile men and ejaculatory duct pressure decreases after transurethral ejaculatory duct resection. [Copyright &y& Elsevier]

Background: The consequences of an infertility diagnosis extend beyond the pursuit of family building, because women with infertility also face increased risks for severe maternal morbidity, cancer, and chronic disease.Objective: This study aimed to examine the association between female infertility and all-cause mortality.Study Design: This retrospective analysis compared 72,786 women with infertility, identified in the Optum Clinformatics Datamart from 2003 to 2019 by infertility diagnosis, testing, and treatment codes, with 3,845,790 women without infertility seeking routine gynecologic care. The baseline comorbidities were assessed using the presence of ≥1 metabolic syndrome diagnoses and the Charlson Comorbidity Index. The primary outcome, which was all-cause mortality, was identified by linkage to the Social Security Administration Death Master File outcomes and medical claims. The association between infertility and mortality was examined using a Cox proportional hazard regression by adjusting for age, hypertension, hyperlipidemia, type II diabetes, year of evaluation, smoking, number of visits per year, nulliparity, obesity, region of the country, and race.Results: Among 16,473,458 person-years of follow-ups, 13,934 women died. Women with infertility had a 32% higher relative risk for death from any cause (0.42% vs 0.35%, adjusted hazard ratio, 1.32; 95% confidence interval, 1.18-1.48) than women without infertility. The mean follow-up time per patient was 4.0±3.7 years vs 4.2±3.8 years for women with and without infertility, respectively. When stratified by age of <35 or ≥35 years or baseline medical comorbidity, the association between infertility and mortality remained. Women with infertility who delivered a child during the follow-up period faced a similar increased risk for mortality than the overall infertile group. Finally, receiving fertility treatment was not associated with a higher risk for death than receiving an infertility diagnosis or testing alone.Conclusion: Although the absolute risk for death was low in both groups, women with infertility faced a higher relative risk for mortality than women without infertility. The association remained across all age, race and ethnicity groups, morbidities, and delivery strata. Importantly, infertility treatment was not associated with an increased risk for death. These findings reinforce the disease burden associated with infertility and its potential for long-term sequelae. [ABSTRACT FROM AUTHOR]

We studied a prospective cohort of 434 couples in Northern California and found that 13% did not pursue any form of infertility treatment after their initial consultation. Although age, education, and financial concerns remain important for patients in choosing whether to pursue infertility treatment, depressive symptoms may also be a barrier to achieving reproductive goals. [ABSTRACT FROM AUTHOR]

Background: Severe maternal morbidity continues to be an issue of national and global concern and is increasing in incidence. The incidence of infertility is also on the rise, and infertile women experience a higher risk of incident chronic medical disease and cancer, suggesting that fertility may serve as a window to a woman's overall health.Objective: To investigate the risk of severe maternal morbidity by maternal fertility status.Materials and Methods: This was a retrospective cohort analysis using Optum's de-identifed Clinformatics Data Mart Database between 2003 and 2015. Infertile women stratified by infertility diagnosis, testing, or treatment were compared to fertile women seeking routine gynecologic care. In both groups, only women who underwent pregnancy and delivery of a singleton during the follow-up period were included. Main outcomes were severe maternal morbidity indicators, defined by the Centers for Disease Control and Prevention and identified by International Classification of Diseases 10th Revision and Common Procedural Technology codes within 6 weeks of each delivery. Results were adjusted for maternal age, race, education, nulliparity, smoking, obesity, delivery mode, preterm birth, number of prenatal visits, and year of delivery.Results: A total of 19,658 women comprised the infertile group and 525,695 women comprised the fertile group. The overall incidence of any severe maternal morbidity indicator was 7.0% among women receiving fertility treatment, 6.4% among women receiving a fertility diagnosis, 5.5% among women receiving fertility testing, and 4.3% among fertile women. Overall, infertile women had a significantly higher risk of developing any severe maternal morbidity indicator (adjusted odds ratio, 1.22; confidence interval, 1.14-1.31, P < .01) as well as a significantly higher risk of disseminated intravascular coagulation (adjusted odds ratio, 1.48; confidence interval, 1.26-1.73, P < .01), eclampsia (adjusted odds ratio, 1.37; confidence interval, 1.05-1.79, P < .01), heart failure during procedure or surgery (adjusted odds ratio, 1.54; confidence interval, 1.21-1.97, P < .01), internal injuries of the thorax, abdomen, or pelvis (adjusted odds ratio, 1.59; confidence interval, 1.12-2.26, P < .01), intracranial injuries (adjusted odds ratio, 1.77; confidence interval, 1.20-2.61, P < .01), pulmonary edema (adjusted odds ratio, 2.18; confidence interval, 1.54-3.10, P < .01), thrombotic embolism (adjusted odds ratio, 1.58; confidence interval, 1.14-2.17, P < .01), and blood transfusion (adjusted odds ratio, 1.50; confidence interval, 1.30-1.72, P < .01) compared to fertile women. Fertile women did not face a significantly higher risk of any maternal morbidity indicator compared to infertile women. In subgroup analysis by maternal race/ethnicity, the likelihood of severe morbidity was significantly higher among fertile black women compared to fertile white women. There was no difference between infertile black women and infertile white women after multivariable adjustment.Conclusion: Using an insurance claims database, we report that women diagnosed with infertility and women receiving fertility treatment experience a significantly higher risk of multiple indicators of severe maternal morbidity compared to fertile women. The increased risk of severe maternal morbidity noted among fertile black women compared to fertile white women is attenuated among infertile black women, who face risks similar to those of infertile white women. [ABSTRACT FROM AUTHOR]

Background: Although in vitro fertilization has been associated with an increased risk for hypertensive disorders of pregnancy, the association of risk with in vitro fertilization treatment parameters is unclear.Objective: To evaluate risk for hypertensive disorders of pregnancy by maternal fertility status and in vitro fertilization treatment parameters.Materials and Methods: Women in 8 states who underwent in vitro fertilization resulting in a live birth during 2004-2013 were linked to their infant's birth certificates. A 10:1 sample of births from non-in vitro fertilization deliveries were selected for comparison. Those with an indication of infertility treatment on the birth certificate were categorized as subfertile and omitted from the study population; all others were categorized as fertile. The in vitro fertilization pregnancies were additionally categorized by oocyte source (autologous versus donor) and embryo state (fresh versus thawed). Both the fertile and in vitro fertilization births were limited to singletons only, and the in vitro fertilization pregnancies were limited to those using partner sperm. Hypertensive disorders of pregnancy (including gestational hypertension and preeclampsia) were identified from the birth certificate, modeled using logistic regression, and reported as adjusted odds ratios and 95% confidence intervals. For analyses of in vitro fertilization pregnancies from autologous oocytes-fresh embryos, the reference group was fertile women (subgroup analysis 1). For analyses within the in vitro fertilization group, the reference group was autologous oocytes-fresh embryos (subgroup analysis 2).Results: The study population included 1,465,893 pregnancies (1,382,311 births to fertile women and 83,582 births to in vitro fertilization-treated women). Compared to fertile women, in vitro fertilization-treated women with autologous-fresh cycles were not at increased risk for hypertensive disorders of pregnancy (adjusted odds ratio, 1.04; 95% confidence interval, 0.99, 1.08). Among in vitro fertilization births (subgroup analysis 2), the risk for hypertensive disorders of pregnancy was increased for the autologous-thawed (adjusted odds ratio, 1.30; 95% confidence interval, 1.20, 1.40); donor-fresh (adjusted oddds ratio, 1.92; 95% confidence interval, 1.71, 2.15); and donor-thawed (adjusted odds ratio, 1.70; 95% confidence interval, 1.47, 1.96) groups. Excluding women with pregestational diabetes or chronic hypertension as well as adjusting for body mass index and infertility diagnoses did not substantially change the results. When stratified by <34 weeks (early-onset hypertensive disorders of pregnancy) versus ≥34 weeks (late-onset hypertensive disorders of pregnancy), only the donor-fresh group had an increased risk of early-onset hypertensive disorders of pregnancy, but the risks for all other oocyte source-embryo state groups compared to autologous-fresh were increased for late-onset hypertensive disorders of pregnancy.Conclusion: The risk for hypertensive disorders of pregnancy is increased for in vitro fertilization-treated women in pregnancies conceived via frozen embryo transfer (with both autologous or donor oocyte) and fresh donor oocyte embryo transfer. No increase in risk was seen with autologous oocyte-fresh embryo transfers in vitro fertilization cycles. Excluding women with pregestational diabetes or chronic hypertension as well as adjusting for body mass index and infertility diagnoses did not substantially change the results. [ABSTRACT FROM AUTHOR]

Background: The risk of common chronic medical conditions among infertile women is not known.Objective: The objective of the study was to study the association between female infertility and the risk of incident chronic disease.Study Design: This was a retrospective cohort analysis using the Optum deidentified Clinformatics Datamart from 2003 through 2016. A total of 64,345 infertile women were identified by infertility diagnosis, testing, or treatment and compared with 3,128,345 noninfertile patients seeking routine gynecologic care. Women with a prior diagnosis of the relevant chronic disease or cancer or with either diagnosis within 6 months of the index event were excluded. The main outcome was a diagnosis of incident chronic disease as identified by International Classification of Diseases, ninth revision/International Classification of Diseases, 10th revision codes. Results were adjusted for age, index year, nulliparity, race, smoking, obesity, number of visits per year, and highest level of education.Results: Infertile patients were more likely to develop diabetes (adjusted hazard risk, 1.44, confidence interval, 1.38-1.49), renal disease (adjusted hazard risk, 1.22, confidence interval, 1.12-1.32), liver disease (adjusted hazard risk, 1.25, confidence interval, 1.20-1.30), cerebrovascular disease (adjusted hazard risk, 1.26, confidence interval, 1.15-1.38), ischemic heart disease (adjusted hazard risk, 1.16, confidence interval, 1.09-1.24), other heart disease (adjusted hazard risk, 1.16, confidence interval, 1.12-1.20), and drug abuse (adjusted hazard risk, 1.24, confidence interval, 1.15-1.33) compared with noninfertile patients. Infertile patients were significantly less likely to develop alcohol abuse (adjusted hazard risk, 0.86, confidence interval, 0.79-0.95) compared with noninfertile patients. Risk associations were similar after excluding women with polycystic ovarian syndrome and premature ovarian insufficiency. In subgroup analyses of women who underwent pregnancy and childbirth during enrollment, several previously noted risk associations were attenuated compared with the overall cohort.Conclusion: While the absolute risk of chronic disease is low, infertility is associated with an increased risk of incident chronic disease compared with a group of noninfertile women. [ABSTRACT FROM AUTHOR]

Male reproduction is a complex process, and numerous medical conditions have the potential to alter spermatogenesis. In addition, male factor infertility may be a biomarker for future health. In the present review, we discuss the current literature regarding the association between systemic diseases and fertility, which may impact clinical outcomes or semen parameters. A number of conditions that have systemic consequences were identified, including genetic (e.g., cystic fibrosis, DNA mismatch repair alterations), obesity, psychological stress, exogenous testosterone, and a variety of common medications. As such, the infertility evaluation may offer an opportunity for health counseling beyond the discussion of reproductive goals. Moreover, male infertility has been suggested as a marker of future health, given that poor semen parameters and a diagnosis of male infertility are associated with an increased risk of hypogonadism, cardiometabolic disease, cancer, and even mortality. Therefore, male fertility requires multidisciplinary expertise for evaluation, treatment, and counseling. [ABSTRACT FROM AUTHOR]

Objective: To report the finding and management of a case of Leydig cell tumor discovered during the infertility evaluation of a patient with mosaic Klinefelter syndrome.Design: Single case report.Setting: Academic hospital.Patient(s): Patient seeking assistance with fertility after a diagnosis of mosaic Klinefelter syndrome.Intervention(s): The patient underwent microscopic testicular sperm extraction (mTESE) for sperm identification after the diagnosis of mosaic Klinefelter syndrome. Abnormal testicular tissue was identified during mTESE and histologically confirmed to be a Leydig cell tumor. The patient was informed of this incidental discovery and later underwent orchiectomy for conservative oncologic control.Main Outcome Measure(s): Histologic testicular assessment.Result(s): Patient was found to have no viable sperm on mTESE, but achieved oncologic control with bilateral orchiectomy.Conclusion(s): The presented case emphasizes the importance of awareness and expedient appropriate management to achieve oncologic control of a rare tumor with low malignant potential discovered during otherwise routine mTESE. In particular, it highlights the role of the infertility specialist in aiding in diagnosis and treatment of incidental and rare findings. [ABSTRACT FROM AUTHOR]

Objective: To examine the National Survey of Family Growth to identify differences in the characteristics of men who did and did not seek infertility care to determine whether such men are representative of the U.S. population. Methods: We analyzed the data from the 2002 (cycle 6) National Survey of Family Growth. In-home interviews were conducted from March 2002 to February 2003. A total of 4928 men were surveyed, with underrepresented groups sampled at greater rates to provide an adequate sample size for meaningful statistical analyses. The use of infertility services was queried by a single question: “Have you been to a doctor to talk about ways to help have a baby together?” The demographic and socioeconomic variables, including age, marital status, number of children, race, religion, income, education, and insurance status were analyzed for the 2161 men surveyed who were aged 30-45 years. We performed bivariate and multivariate logistic regression analyses to determine the predictors of infertility service use. Results: Marital status and education level were strongly associated with infertility care seeking. In the adjusted analysis, married men were 9 times (odds ratio 9.3, 95% confidence interval 4.1-20.9) more likely to seek care than unmarried men, and men with a college degree and those with an advanced degree were 3 times (odds ratio 2.7, 95% confidence interval 1.4-5.0) and 5 times (odds ratio 4.7, 95% confidence interval 2.1-10.5) more likely to seek care, respectively. Conclusion: Men seeking infertility care in the United States tend to be married, older, and more educated than those not seeking care. Given these findings, some results of male infertility studies from cohorts of men from infertility referral centers might not apply to the U.S. population. [ABSTRACT FROM AUTHOR]

Male reproduction is a complex biological process, and male factor infertility is increasingly recognized as a biomarker for overall male health. Emerging data suggest associations between male reproduction and medical disease (genetic, infectious, chronic comorbid conditions), psychological disease, environmental exposures, dietary habits, medications and substances of abuse, and even socioeconomic factors. There is also evidence that a diagnosis of male fertility is associated with future disease risk including cancer, metabolic disease and mortality. As such, there is a growing view that the male fertility evaluation is an opportunity to improve a man's health beyond his immediate reproductive goals, and also highlights the necessity of a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Purpose: The summary presented herein represents Part I of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part I outlines the appropriate evaluation of the male in an infertile couple. Recommendations proceed from obtaining an appropriate history and physical exam (Appendix I), as well as diagnostic testing, where indicated.Materials/methods: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January, 2000 through May, 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. (Table 1) This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology.Results: This Guideline provides updated, evidence-based recommendations regarding evaluation of male infertility as well as the association of male infertility with other important health conditions. The detection of male infertility increases the risk of subsequent development of health problems for men. In addition, specific medical conditions are associated with some causes for male infertility. Evaluation and treatment recommendations are summarized in the associated algorithm. (Figure 1) CONCLUSION: The presence of male infertility is crucial to the health of patients and its effects must be considered for the welfare of society. This document will undergo updating as the knowledge regarding current treatments and future treatment options continues to expand. [ABSTRACT FROM AUTHOR]