Search

STUDY QUESTION Are follicular fluid (FF), arsenic (As), mercury (Hg), cadmium (Cd) and lead (Pb) concentrations associated with IVF outcomes among women undergoing IVF? SUMMARY ANSWER There was a non-linear association between higher FF Hg concentration and a lower likelihood of biochemical pregnancy and live birth. Higher FF Pb concentration was also associated with a lower probability of live birth. WHAT IS KNOWN ALREADY Previous research suggests that toxic elements may affect fertility among couples conceiving with and without assistance. However, the results have been inconsistent, possibly related in part to exposure misclassification. Very few studies have used ovarian FF to measure toxic elements, as it requires an invasive collection procedure, yet it may offer a more accurate estimate of a biologically effective dose than blood or urine. STUDY DESIGN, SIZE, DURATION This is a prospective study of 56 women undergoing IVF, from October 2015 to June 2017. FF was collected for analysis on the day of oocyte retrieval. PARTICIPANTS/MATERIALS, SETTING, METHODS As, Cd, Hg and Pb were determined in 197 FF specimens, using inductively coupled plasma tandem mass spectrometry. FF glutathione peroxidase, glutathione reductase, total glutathione-S-transferase, superoxide dismutase, arylesterase and paraoxonase (PON1p) activities were measured using kinetic enzyme assays. MAIN RESULTS AND THE ROLE OF CHANCE Non-linear associations were detected, in which the probabilities of biochemical pregnancy (P  = 0.05) and live birth (P  = 0.05) were lower in association with FF Hg greater than ∼0.51 µg/l Hg, adjusted for age, race, cigarette smoking and recent seafood consumption. Higher FF Pb was also associated with a lower likelihood of live birth (relative risk (RR) = 0.68, 95% CI: 0.46, 1.00; P  = 0.05). We also found a suggestive, although imprecise, antagonizing mediating effect of PON1p activity on the association between FF Pb and live birth (−28.3%; 95% CI: −358%, 270%). LIMITATIONS, REASONS FOR CAUTION The results should be interpreted judiciously given the limited sample size and difficulty accounting for correlated data in generalized additive models and mediation analyses. Additionally, women undergoing IVF are highly selected with respect to age and socioeconomic status, and so the generalizability of the results may be limited. WIDER IMPLICATIONS OF THE FINDINGS Overall, the results suggest that FF Hg was associated with a lower likelihood of biochemical pregnancy and live birth, with a potential threshold effect, and that higher FF Pb was associated with a lower probability of live birth. These results may help to guide clinical recommendations for limiting the exposure of patients to Hg and Pb and ultimately improve IVF success rates. STUDY FUNDING/COMPETING INTEREST(S) This work was funded in part by the National Institute of Environmental Health Sciences (NIEHS), grant number 1R56ES023886-01, to the University at Albany (M.S.B.), and in part by the National Institute of Environmental Health Sciences (NIEHS), grant number 1U2CES026542-01, to the Wadsworth Center (P.J.P.). The authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A [ABSTRACT FROM AUTHOR]

Objective  This study aimed to assess the association of preimplantation genetic testing (PGT) with abnormal placentation among a cohort of pregnancies conceived after frozen embryo transfer (FET). Study Design  This is a retrospective cohort study of women who conceived via FET at the University of California, San Francisco from 2012 to 2016 with resultant delivery at the same institution. The primary outcome was abnormal placentation, including placenta accreta, retained placenta, abruption, placenta previa, vasa previa, marginal or velamentous cord insertion, circumvallate placenta, circummarginate placenta, placenta membranacea, bipartite placenta, and placenta succenturiata. Diagnosis was confirmed by reviewing imaging, delivery, and pathology reports. Our secondary outcome was hypertensive disease of pregnancy. Results  A total of 311 pregnancies were included in analysis; 158 (50.8%) underwent PGT. Baseline demographic characteristics were similar between groups except for age at conception and infertility diagnosis. Women with PGT were more likely to undergo single embryo transfer (82.3 vs. 64.1%, p  < 0.001). There were no statistically significant differences in the rate of the primary outcome (26.6 vs. 27.4%, p  = 0.86) or hypertensive disorders of pregnancy (33.5 vs. 33.3%, p  = 0.97), which remained true after multivariate analysis was performed. Conclusion  Among pregnancies conceived after FET, PGT is not associated with a statistically significant increased risk of abnormal placentation or hypertensive disorders of pregnancy. Key Points In pregnancies conceived by FET, PGT is not associated with increased risk of abnormal placentation. In pregnancies conceived by FET, PGT is not associated with increased risk of hypertensive disorders. Differences in outcomes of PGT pregnancies may be related to FET rather than trophectoderm biopsy. [ABSTRACT FROM AUTHOR]

Follicular fluid (FF), which is the fluid that envelops the developing oocyte (egg cell) in the ovary, can be analyzed to assess trace element content as well as to determine potential exposure to toxic elements in women seeking in vitro fertilization (IVF) treatment. Such measurements may be useful in establishing associations with potential adverse effects on oocyte viability and subsequent pregnancy outcomes. The principal goal of this study was to leverage the next generation of inorganic mass spectrometry based on ICP-MS/MS to address the numerous analytical challenges of (ultra-)trace element analysis of human FF specimens. Ultra-trace element measurements are defined by the Clinical Laboratory Standards Institute as fluid concentrations below 10 μg L−1 or tissue mass fractions below 1 μg g−1. Stringent pre-analytical procedures were developed to minimize exogenous contamination during FF specimen collection and storage in a prospective study of 56 women seeking IVF treatment. ICP-MS/MS instrumental parameters were carefully optimized, and the method validated for 11 biologically important elements that included 4 at trace levels (Cu, Se, Sr, and Zn) and 7 at ultra-trace levels (As, Cd, Co, Mo, Mn, Hg, and Pb). Method limits of detection (LODs) for ultra-trace elements varied from 5.6 ng L−1 for Cd to 0.11 μg L−1 for Mo. A total of 197 human FF specimens were analyzed using the proposed ICP-MS/MS method with 84% of specimens detectable for Pb and 100% detectable for Co, Cu, Mn, Mo, Sr, and Zn. The method based on ICP-MS/MS was compared to a previous method developed for FF using SF-ICP-MS. [ABSTRACT FROM AUTHOR]

Bisphenol A is widely used as a component in polycarbonate plastics for food and beverage packaging, epoxy linings for canned foods, and dental sealants, among other applications. Experimental literature demonstrates BPA's affinity for estrogen receptors and downstream effects on estrogen-responsive genes. Additional data suggest that BPA reduces endogenous estrogen synthesis, likely by antagonizing ovarian enzyme activities involved in sex-steroid hormone synthesis. More specifically, evidence indicates BPA-mediated disruption of STAR, CYP450scc, and HSD-3β in theca cells and CYP450 aromatase activity in granulosa cells. Yet the results of the few human studies reported to date are equivocal. It also remains in question the extent to which BPA penetrates developing ovarian follicles. Uncertainty as to the relevance of experimental BPA doses and administration routes for common human exposure levels limits extrapolation of experimental results. To more definitively address the potential risk of BPA on human ovarian steroidogenesis, additional experimental studies using biologically active BPA doses likely to reflect those within the ovarian follicle will be necessary, as will additional prospective investigations in human populations with the use of standardized assay methodology. [ABSTRACT FROM AUTHOR]

Both essential and non-essential elements have been associated with female reproductive function in epidemiologic investigations, including among IVF populations. To date, most investigators have used blood or urine to assess biomarkers of exposure, with few employing ovarian follicular fluid (FF). FF may offer a more direct "snapshot" of the oocyte microenvironment than blood or urine, however previous studies report follicle-to-follicle variability in FF constituents that may contribute to exposure misclassification. Our objectives were to investigate sources of trace element variability, to estimate FF biomarker reliability among women undergoing IVF (n = 34), and to determine the minimum number of follicles required to estimate subject-specific mean concentrations. We measured As, Hg, Cd, Pb, Cu, Mn, Se, and Zn in FF samples using inductively coupled plasma tandem mass spectrometry. Inter-subject (between-women) variability contributed most of the variability in FF element concentrations, with ovarian, follicular, and analytical as smaller sources of variability. The proportion of variability attributable to sources between-follicles differed by age, body mass index (BMI), race, and cigarette smoking for Cu, Se, and Zn, by BMI and cigarette smoking for As, by primary infertility diagnosis for Hg, Cu, Se, and Zn, and by ovarian stimulation protocol for Mn and Se. Four to five individual follicles were sufficient to estimate subject-specific mean Cu, Se, and Zn concentrations, while >14 were necessary for As, Hg, Cd, Pb, and Mn. Overall, our results suggest that FF is a suitable source of biomarkers of As and Hg exposure in ovarian follicles. Although limited in size, our study offers the most comprehensive exploration of biological variation in FF trace elements to date and may provide guidance for future studies of ovarian trace element exposures. ga1 • Follicle-to-follicle variability in follicular fluid (FF) trace elements may contribute to exposure misclassification. • We measured As, Hg, Cd, Pb, Cu, Mn, Se, and Zn in FF samples using inductively coupled plasma tandem mass spectrometry. • Sources between women contributed the greatest proportion of total measured variability for most FF trace elements. • Biologic variation of trace elements was impacted by demographic and clinical factors also associated with IVF outcomes. • FF is a suitable source of biomarkers of As and Hg contamination in the follicle. [ABSTRACT FROM AUTHOR]

Objective: To assess the attitudes of the general U.S. population toward the use of IVF to assist adults with a history of cancer or human immunodeficiency virus (HIV). Design: Cross-sectional survey study. Setting: Online. Patient(s): A total of 1,183 adult men and women across the U.S. Intervention(s): Questionnaire consisting of multiple-choice and open-ended questions. Main Outcome Measure(s): Attitudes toward IVF for cancer and HIV patients. Result(s): A total of 82% supported IVF for cancer patients compared with 38% for HIV patients. The most common reasons for support was the anticipation of normal life expectancies and a belief in the universal right to have children, although nearly twice as many participants believed this to be a “right” for cancer patients than for HIV patients. Young respondent ages, higher educational attainment, Jewish religion, and a personal history of infertility were associated with higher likelihood of support. Lower education level, higher annual household income, and having children were predictors of discordance in support of IVF for cancer versus HIV patients. Conclusion(s): Despite advancements in the treatment of cancer and HIV, which have allowed patients to have longer life expectancies and improved chances of parenthood, there is significant disparity in the support of providing IVF to these patient groups. [Copyright &y& Elsevier]

Objective: To report on the semen quality parameters in transgender women who pursued semen cryopreservation either in the presence or absence of gender-affirming hormonal medication.Materials and Methods: This retrospective cohort study was conducted as a chart review of consecutive transgender women presenting for semen cryopreservation between January 1, 2012 and March 31, 2018. Demographic data and semen parameters were assessed. Primary outcomes were the semen parameters in subjects with either no exposure, previous exposure or current exposure to gender-affirming hormonal medication.Results: Twenty-eight patients presented for semen cryopreservation and produced 69 specimens. Using a Kruskal-Wallis test, semen analyses were compared between patients who had never used gender-affirming hormonal medication, those who had previously used hormonal medication but discontinued prior to specimen collection, and those who used medication at the time of specimen collection. Median semen parameters for each group were as follows: volume-2.7 mL, 2.1 mL, 0.9 mL, respectively (P = .12); concentration-63.6 M/mL, 39.0 M/mL, 2.4 M/mL, respectively (P < .01); percent motility-51.5%, 34.3%, 15.6%, respectively (P < .01); and the total motile count was 63.2 M,39.1 M, 0.2 M, respectively (P < .01). Fifteen specimens were collected after discontinuing hormonal medication with a mean discontinuation period of 4.4 months.Conclusion: Specimens collected in the presence of hormonal medication were associated with abnormal semen parameters. Specimens collected after discontinuation of gender-affirming treatments were comparable to transgender women who had never used hormonal medication. Transgender women should be counseled about the potential impact of gender-affirming hormones and to consider fertility preservation prior to gender-affirming treatments. [ABSTRACT FROM AUTHOR]

Ensuring harmonization of (ultra-)trace element measurements in non-traditional matrices is a particular analytical challenge that is highlighted in this work for seminal plasma as part of the developmental core at the Wadsworth Center Human Health Exposure Analysis Resource Targeted Laboratory. Seminal plasma was collected from 39 male partners of women undergoing in vitro fertilization and analyzed by inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) following deproteinization with concentrated HNO3. Validation was accomplished using: 1) two aqueous NIST SRMs; 2) a seminal plasma QC pool, characterized via standard additions; 3) standard additions on a subset of samples; and 4) sample duplicates. Agreement with NIST certified or reference values were obtained to within ±15% for the SRMs, and agreement between aqueous calibration values and standard additions values agreed to within ±10-20% for all elements. Standard additions of seminal plasma samples revealed varying matrix effects for Cu and Cr that were not found for the pooled samples. Duplicate analyses agreed to within ±10-30% depending on element. A potential source of contamination in colloidal silica used for processing seminal plasma was identified that requires further study. Comparisons with literature indicate lack of consensus for As, Cd, Cr, Mn, Pb, and V content in seminal plasma. Further work is needed to improve harmonization of future studies. [ABSTRACT FROM AUTHOR]

Human exposure to non-essential toxic metals such as cadmium (Cd), mercury (Hg), and lead (Pb), and metalloids such as arsenic (As) commonly occurs through diet. Toxic trace element exposures have been reported in association with fertility and fecundity in epidemiologic studies even at low to moderate levels. While most previous studies employed blood and urine biomarkers of exposure, few have assessed toxic trace elements in ovarian follicular fluid (FF), which surrounds the developing oocyte and hence may better reflect concentrations potentially affecting reproductive outcomes. Our objective was to identify dietary predictors of FF toxic trace elements in n = 56 women (mean age: 38.3 years) undergoing in vitro fertilization (IVF) at the University of California at San Francisco. We determined As, Hg, Cd, and Pb in 197 FF specimens, collected on the day of oocyte retrieval, using inductively coupled plasma tandem mass spectrometry. A comprehensive food frequency questionnaire was used to assess the weekly and annual dietary "patterns" of participants. Consumption of specific seafood items and turkey were correlated with individual FF toxic trace elements. We also found that each unit higher seafood consumption in the past week dominated by mollusks, shrimp, and bass was associated with 60% higher FF As (95% confidence interval (CI): 25%, 105%) and FF Hg (95%CI: 7%, 136%) concentrations. Higher annual seafood consumption dominated by urchin, crab, and trout was associated with 16% higher FF As (95%CI: −2%, 38%) and 31% higher FF Hg (95%CI: 7%, 60%) concentrations per unit intake. No associations were noted between diet and Cd and Pb levels in FF. Overall, our results suggest that higher seafood consumption contributes to elevated levels of As and Hg in FF. These findings are consistent with previous IVF studies that assessed toxic trace element exposures in blood and urine. To our knowledge, this is the first study to report that diet might be a source of As, Hg, Cd, and Pb in FF. Image 1 • Diet is a common source of exposure to toxic trace elements. • We measured arsenic, mercury, cadmium, and lead in human ovarian follicular fluid. • Heavy seafood intake was associated with higher follicular fluid As and Hg levels. • Dietary interventions may be useful in limiting ovarian As and Hg exposures. [ABSTRACT FROM AUTHOR]

Phthalates have been implicated as reproductive toxicants in animal models and in human populations. This study examined associations between potential exposure sources and urinary phthalate metabolite concentrations among women (n = 56) and their male partners (n = 43) undergoing in vitro fertilization (IVF). On the day of oocyte retrieval, participants provided urine samples and completed questionnaires detailing use of personal care products (PCPs), and consumption of medications, foods, and beverages in the preceding 24 h. Urine was analyzed for MEP, MBP, MPP, MHxP, MEHP, MEHHP, MECPP, MiNP, MiDP, MCHP, and MBzP, via liquid chromatography-tandem mass spectrometry. We employed principal component analysis (PCA) to summarize exposure sources and regression models to estimate associations between exposure patterns and urinary phthalate metabolites, adjusted for confounding variables. Among women, application of more body washes and eye creams, and consumption of more supplements, was associated with greater urinary MECPP [relative difference = 1.36 (95% CI: 1.28, 1.45)] and the molar sum of DEHP metabolites, including MEHP, MEHHP, and MECPP [∑DEHP; 1.26 (95% CI: 1.17, 1.34)]. Among men, consumption of more supplements and allergy medications was associated with greater urinary MECPP, MEHHP, and ∑DEHP [relative difference = 1.13 (95% CI: 1.02, 1.23)] concentrations. Identifying differences in sources of phthalate exposure may help clinicians to intervene to reduce exposure as part of a comprehensive strategy to help improve IVF outcomes. [ABSTRACT FROM AUTHOR]

Objective: To report two cases of fertility preservation in two transgender men without an extended period of higher dose testosterone cessation., Design: Chart abstraction was completed for two cases of oocyte preservation in transgender men without stopping testosterone gender-affirming therapy before controlled ovarian stimulation (COS)., Setting: A university-affiliated fertility clinic in San Francisco, California., Patients: Two 27-year-old transgender men on higher dose testosterone undergoing oocyte cryopreservation., Interventions: Not applicable., Main Outcome Measures: Both patients had been on 6 and 20 months of testosterone therapy, respectively, and continued throughout COS. A random start antagonist plus letrozole protocol was used for the patient in case 1, with a leuprolide acetate trigger. A luteal start antagonist protocol was applied to the patient in case 2 with a leuprolide acetate trigger., Results: In case 1, a total of 35 oocytes were retrieved, with a total of 23 metaphase II (MII) oocytes cryopreserved. An additional 7 MII oocytes were obtained after in vitro maturation for a total of 30 MII oocytes that were vitrified. In case 2, 14 oocytes were retrieved, and 9 mature oocytes (MII) were vitrified., Conclusions: Transgender men have historically been advised to discontinue testosterone before COS, a process that may be distressing for many individuals. This is the first published case report demonstrating the proof of concept of COS without cessation of high-dose testosterone therapy in two transgender men. Future studies with larger sample sizes should be performed to confirm these findings., (© 2022 The Authors.)

Müllerian duct anomalies (MDAs) have important implications for the reproductive health of female patients. In patients with both infertility and recurrent pregnancy loss, the incidence of MDAs is as high as 25%. Congenital uterine anomalies are often only part of a complex set of congenital anomalies involving the cervix, vagina, and urinary tract. Multiple classification systems for MDAs exist, each with different criteria that vary most for the diagnosis of septate uterus. Recognizing the features that guide clinical management is essential for interpretation. Identification of an MDA should prompt evaluation for associated urinary tract anomalies. In patients with infertility who seek to use assisted reproductive technologies such as intrauterine insemination, recognition of MDAs may have an affect on reproductive success, particularly in patients who have an incomplete and clinically occult septum that divides the cervix. Two-dimensional US is the first-line modality for evaluating the uterus and adnexa. Three-dimensional (3D) US or MRI may help to visualize the external uterine fundal contour and internal indentation of the endometrial cavity, which are two morphologic characteristics that are keys to the diagnosis of congenital uterine anomalies. Hysterosalpingo contrast-enhanced US may be performed in conjunction with 3D US to evaluate uterine morphologic characteristics, the endometrial cavity, and tubal patency in a single examination. MRI helps to characterize rudimentary uteri in patients with müllerian hypoplasia and allows assessment for ectopic ureters, abnormally positioned ovaries, or associated deep infiltrative endometriosis. Online supplemental material is available for this article. ©RSNA, 2021.

Objective: To assess attitudes and factors that influence public opinion in the general US population toward insurance coverage and provision of infertility care to lower income patients., Design: Cross-sectional survey., Setting: Online., Patients: A nationally representative sample of US residents., Interventions: Questionnaire with multiple choice and open response questions., Main Outcome Measures: Public attitudes toward in vitro fertilization and infertility care coverage for lower income patients., Results: A total of 1,027 (90.2%) participants completed the survey, among whom 620 (60.4%) had private insurance, 275 (26.8%) had Medicare/Medicaid, and 56 (5.5%) were uninsured. The majority (916, 89.2%) did not consider infertility a disease. Over half of the respondents (568, 55.3%) supported private insurance coverage of infertility services, including for in vitro fertilization. Most respondents, 735 (71.6%) believed that the prevalence and psychosocial impact of infertility were equal among the lower and higher income people. The majority of respondents with an opinion (512, 67.6%) believed that doctors should provide infertility treatments regardless of the income level of the patients. Of supporters, 40.1% believed in the right to have a family regardless of income, and 38.2% believed that doctors had a social responsibility to provide infertility services. After adjusting for covariates, age <45 years, noncollege graduates, desiring more children, believing that infertility was a disease, and residence in the Northeast region remained significant predictors for support of private insurance coverage., Conclusions: Public perception of infertility as a disease is one of the strongest predictors of support for insurance coverage for infertility services, underscoring the need for enhanced advocacy and education in the general public., (© 2021 The Authors.)

Follicular fluid (FF), which is the fluid that envelops the developing oocyte (egg cell) in the ovary, can be analyzed to assess trace element content as well as to determine potential exposure to toxic elements in women seeking in vitro fertilization (IVF) treatment. Such measurements may be useful in establishing associations with potential adverse effects on oocyte viability and subsequent pregnancy outcomes. The principal goal of this study was to leverage the next generation of inorganic mass spectrometry based on ICP-MS/MS to address the numerous analytical challenges of (ultra-)trace element analysis of human FF specimens. Ultra-trace element measurements are defined by the Clinical Laboratory Standards Institute as fluid concentrations below 10 μg L -1 or tissue mass fractions below 1 μg g -1 . Stringent pre-analytical procedures were developed to minimize exogenous contamination during FF specimen collection and storage in a prospective study of 56 women seeking IVF treatment. ICP-MS/MS instrumental parameters were carefully optimized, and the method validated for 11 biologically important elements that included 4 at trace levels (Cu, Se, Sr, and Zn) and 7 at ultra-trace levels (As, Cd, Co, Mo, Mn, Hg, and Pb). Method limits of detection (LODs) for ultra-trace elements varied from 5.6 ng L -1 for Cd to 0.11 μg L -1 for Mo. A total of 197 human FF specimens were analyzed using the proposed ICP-MS/MS method with 84% of specimens detectable for Pb and 100% detectable for Co, Cu, Mn, Mo, Sr, and Zn. The method based on ICP-MS/MS was compared to a previous method developed for FF using SF-ICP-MS.