Browsing by Subject "Fertility"

Now showing 1 - 10 of 11
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    Coiled-coil domain containing 42 (Ccdc42) is necessary for proper sperm development and male fertility in the mouse
    (Elsevier, 2016-04-15) Pasek, Raymond C.; Malarkey, Erik; Berbari, Nicolas F.; Sharma, Neeraj; Kesterson, Robert A.; Tres, Laura L.; Kierszenbaum, Abraham L.; Yoder, Bradley K.; Department of Biology, School of Science
    Spermiogenesis is the differentiation of spermatids into motile sperm consisting of a head and a tail. The head harbors a condensed elongated nucleus partially covered by the acrosome-acroplaxome complex. Defects in the acrosome-acroplaxome complex are associated with abnormalities in sperm head shaping. The head-tail coupling apparatus (HTCA), a complex structure consisting of two cylindrical microtubule-based centrioles and associated components, connects the tail or flagellum to the sperm head. Defects in the development of the HTCA cause sperm decapitation and disrupt sperm motility, two major contributors to male infertility. Here, we provide data indicating that mutations in the gene Coiled-coil domain containing 42 (Ccdc42) is associated with malformation of the mouse sperm flagella. In contrast to many other flagella and motile cilia genes, Ccdc42 expression is only observed in the brain and developing sperm. Male mice homozygous for a loss-of-function Ccdc42 allele (Ccdc42(KO)) display defects in the number and location of the HTCA, lack flagellated sperm, and are sterile. The testes enriched expression of Ccdc42 and lack of other phenotypes in mutant mice make it an ideal candidate for screening cases of azoospermia in humans.
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    Count-Regression-Based Empirical Causal Analysis from a Potential Outcomes Perspective: Accounting for Boundedness, Discreteness, Dispersion and Unobservable Confounding
    (2024-06) Kazeminezhad, Golnoush; Terza, Joseph V.; Harle, Christopher A.; Morrison, Wendy; Russell, Steven
    Empirical economic research is primarily driven by the desire to offer scientific evidence that serves to inform the study of cause-and-effect. In this dissertation, I developed new models for count-regression-model-based (CRM-based) causal effect estimation in which the value for the outcome of interest is restricted to the non-negative integers. I implement first-order two-stage residual inclusion (FO-2SRI) methods, in the context of the general potential outcomes framework, that accommodate nonlinearities due to the intrinsic characteristics of count-valued outcomes such as boundedness (outcome nonnegative), discreteness (outcome has countable support) and dispersion (conditional variance and other higher order conditional moments of the outcome not necessarily equal to its conditional mean) of count data, and unobservable confounding. The focus here is on the case in which the causal variable is continuous. The newly proposed causal effect estimators are compared with extant FO-2SRI estimators based on conventional control function methods and the linear instrumental variables (LIV) estimator. A series of simulation studies are performed to investigate the accuracy of the proposed estimators and compare the results with the extant estimators. In the simulation studies, the robustness of the fully nonlinear CRM-based FO-2SRI methods are investigated with attention to an important type of misspecification error. The models are also applied to a real-world data from Nigeria to investigate the effect of female education on their fertility decisions in a developing country. The results of the simulation studies reveal that estimates obtained via the newly proposed estimators are very accurate and widely diverge from the results from the extant control function and LIV methods. Moreover, one of the new estimators, which allows dispersion flexibility, dominated all other estimators (aside from a few extreme dispersion cases) with regard to avoidance of misspecification bias. Finally, the results showed that same estimator to be quite accurate for a wide range of values of the dispersion parameter (which measures mean/variance divergence). Similar results were obtained via the real data analysis which indicates that increasing women’s education decreases childbearing.
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    Decision Making in Fertility Preservation Prior to Pursuing Curative Treatments for Sickle Cell Disease
    (2023-03-24) Collins, Angela J.; Noel, Josey; Abraham, Olivia; Hornberger, Sydney; Rahim, Mahvish Q.; Jacob, Seethal A.; Saraf, Amanda J.
    AUTHORS: Angela Collins, MPH(1), Josey Noel(1), Olivia Abraham(1), Sydney Hornberger(1), Mahvish Rahim MD, MBA, MSCR(1,2), Seethal Jacob MD, MS, FAAP(1,2), Amanda Saraf DO(1,2). AFFILIATIONS: (1) Indiana University School of Medicine, Indianapolis, IN. (2) Department of Pediatrics, Riley Hospital for Children, Indianapolis, IN. ABSTRACT: RELEVANT BACKGROUND: Sickle cell disease (SCD) is one of the most commonly inherited hemoglobinopathies, often well controlled on Hydroxyurea (HU). Curative therapy options exist with stem cell transplant (SCT) and gene therapy. While both the underlying condition and routine therapy such as HU is thought to impact fertility, the chemotherapy used for both SCT and gene therapy can result in permanent sterility. Infertility can have a negative impact on long-term measures of quality of life. As a result, fertility preservation ought to be offered to all patients with SCD planning for curative treatment. Ovarian tissue cryopreservation and mature oocyte or embryo cryopreservation are fertility preservation options available for pre and postpubescent females respectively. Testicular tissue cryopreservation (TTC) is an experimental option for prepubescent males and sperm cryopreservation is utilized for postpubescent males. CASE DESCRIPTION: We present three cases of patients with SCD who pursued fertility preservation prior to receiving curative therapy with a myeloablative preparative regimen. Patient 1 is a prepubescent 8-year-old male with SCD controlled with HU who opted for TTC as fertility preservation prior to receiving a matched sibling SCT. Patient 2 is a 13-year-old male with SCD controlled with HU who opted for TTC following a failed sperm banking attempt prior to haploidentical SCT. Patient 3 is an 18-year-old female with SCD controlled with HU and Voxelator who opted to have eggs harvested prior to gene therapy. CLINICAL SIGNIFICANCE: As highlighted by these cases, continued research on safe and effective fertility preservation as well as counseling about both the impact of the underlying disease on fertility and treatment-related fertility risks is imperative to improve long-term quality of life measures. CONCLUSION: These patients demonstrate a need for further emphasis on fertility risk counseling in this patient population and ensuring that discussions regarding preservation options is standard of practice at every institution.
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    Deletion of Arid1a in Reproductive Tract Mesenchymal Cells Reduces Fertility in Female Mice
    (Society for the Study of Reproduction, 2016-04) Wang, Xiyin; Khatri, Shikha; Broaddus, Russell; Wang, Zhong; Hawkins, Shannon M.; Department of Obstetrics and Gynecology, School of Medicine
    Women with endometriosis can suffer from decreased fecundity or complete infertility via abnormal oocyte function or impaired placental-uterine interactions required for normal pregnancy establishment and maintenance. Although AT-rich interactive domain 1A (SWI-like) (ARID1A) is a putative tumor suppressor in human endometrial cancers and endometriosis-associated ovarian cancers, little is known about its role in normal uterine function. To study the potential function of ARID1A in the female reproductive tract, we generated mice with a conditional knockout of Arid1a using anti-Müllerian hormone receptor 2-Cre Female Arid1a conditional knockout mice exhibited a progressive decrease in number of pups per litter, with a precipitous decline after the second litter. We observed no tumors in virgin mice, although one knockout mouse developed a uterine tumor after pregnancy. Unstimulated virgin female knockout mice showed normal oviductal, ovarian, and uterine histology. Uteri of Arid1a knockout mice showed a normal decidualization response and appropriate responses to estradiol and progesterone stimulation. In vitro studies using primary cultures of human endometrial stromal fibroblasts revealed that small interfering RNA knockdown of ARID1A did not affect decidualization in vitro. Timed pregnancy studies revealed the significant resorption of embryos at Embryonic Day 16.5 in knockout mice in the third pregnancy. In addition to evidence of implantation site hemorrhage, pregnant Arid1a knockout mice showed abnormal placental morphology. These results suggest that Arid1a supports successful pregnancy through its role in placental function.
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    Economic Uncertainty and Fertility
    (University of Chicago Press, 2021) Gozgor, Giray; Bilgin, Mehmet Huseyin; Rangazas, Peter; Economics, School of Liberal Arts
    The precautionary motive for saving predicts that an increase in income uncertainty increases saving by reducing both consumption and fertility. We examine this prediction using a new measure of economic uncertainty—the World Uncertainty Index—and focus on data from 126 countries for the period 1996–2017. The empirical findings indicate that uncertainty decreases the fertility rate, as suggested by theory. This evidence is robust to different model specifications and econometric techniques as well as to the inclusion of various controls. The evidence also indicates that changes in uncertainty may be a factor explaining why fertility is procyclical.
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    Fertility counseling information adequacy as a moderator of regret among adolescent and young adult breast cancer survivors
    (Springer, 2021) Campbell, Angela G.; Hillemeier, Marianne; Pediatrics, School of Medicine
    Purpose: Current literature disagrees on whether fertility counseling decreases or increases decision regret among young breast cancer survivors. This study investigates whether fertility counseling provided to pre-menopausal breast cancer patients regarding infertility due to treatment is associated with decision regret post-treatment, and how that relationship is moderated by information adequacy. Methods: Breast cancer patients aged 18-35 listed in the Pennsylvania Cancer Registry as diagnosed between 2007 and 2012 were surveyed. Basic descriptive analyses were conducted, and linear regression models were estimated. Results: Receipt of fertility counseling was not directly associated with decision regret. However, as fertility information adequacy increased, decision regret significantly decreased among women who received fertility counseling after finishing treatment or before and after finishing treatment. On average, a woman who receives fertility counseling before and after treatment with an information adequacy score of 1.5 had a regret score of 2.68. In contrast, a woman who received fertility counseling before and after treatment who had a fertility information adequacy score of 5 had a regret score of only 1.26 on average. Conclusion: Information adequacy is a significant moderator in the relationship between fertility counseling and decision regret. This suggests a possible explanation for disagreement in the literature regarding the benefits of fertility counseling and highlights the need for an increased focus on the adequacy of the information provided. Implications for cancer survivors: Fertility counseling should be pursued for young adult breast cancer patients and survivors, provided that their satisfaction with the information received is monitored and remains high.
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    Hyaluronidase 6 Does Not Affect Cumulus-Oocyte Complex Dispersal and Male Mice Fertility
    (MDPI, 2022-04-25) Bang, Hyewon; Lee, Sujin; Jeong, Pil-Soo; Seol, Dong-Won; Son, Daeun; Kim, Young-Hyun; Song, Bong-Seok; Sim, Bo-Woong; Park, Soojin; Lee, Dong-Mok; Wee, Gabbine; Park, Joon-Suk; Kim, Sun-Uk; Kim, Ekyune; Biochemistry and Molecular Biology, School of Medicine
    Glycosylphosphatidylinositol-anchored sperm hyaluronidases (HYAL) assist sperm penetration through the cumulus-oocyte complex (COC), but their role in mammalian fertilization remains unclear. Previously, we demonstrated that sperm from HYAL 5 and 7 double-knockout (dKO) mice produced significantly less offspring than sperm from wild-type mice due to defective COC dispersal. However, the HYAL6 gene remained active in the sperm from the dKO mice, indicating that they were not entirely infertile. This study explored the role of HYAL6 in fertilization by analyzing HYAL6-mutant mice. In this mouse model, HYAL5 and HYAL7 were present in the HYAL6-knockout sperm, and they could disperse hyaluronic acid. We found that HYAL6 was present on the surface of sperm. However, male mice lacking the HYAL6 gene had normal fertility, testicular integrity, and sperm characteristics. Furthermore, in vitro fertilization assays demonstrated that HYAL6-deficient epididymal sperm functioned normally. Therefore, HYAL6 is dispensable for fertilization.
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    Managing Uncertainty: Women's Perceptions of the COVID-19 Vaccine and Fertility
    (2023-05) Broeker, Chloe Elaine; Brann, Maria; Bute, Jennifer; Head, Katharine
    During the last two years, women of reproductive age (WRA) have experienced uncertainty about the COVID-19 vaccine, particularly as it relates to reproductive health (e.g., fertility) due to the COVID-19 infodemic. Because WRA are a pivotal population in pandemic control, it is important to understand how WRA manage vaccine-related uncertainty. Uncertainty management theory (UMT) considers the complexities of uncertainty, acknowledging that individual appraisals of, and responses to, uncertainty may vary from person to person and evolve over time. This study examined factors contributing to WRA’s hesitancy to receive the COVID-19 vaccine, including uncertainty about potential side effects, concern about safety and efficacy, and conflicting information. WRA most frequently felt neutral towards their uncertainty; however, negative emotional responses to uncertainty played an influential role in many WRA’s responses to uncertainty (e.g., avoiding information, seeking information, receiving the COVID-19 vaccine). The findings of this study provided insight on how WRA have experienced uncertainty about the COVID-19 vaccine, including their emotional responses to and subsequent appraisals of their uncertainty which ultimately influenced their responses.
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    Maternal fluoride exposure, fertility and birth outcomes: The MIREC cohort
    (Elsevier, 2022-04) Goodman , Carly; Hall , Meaghan; Green , Rivka; Hornung , Richard; Martinez-Mier , Esperanza Angeles; Lanphear , Bruce; Till, Christine; Dental Public Health and Dental Informatics, School of Dentistry
    Objective Fluoride exposure >1.5 mg/L from water has been associated with adverse pregnancy and birth outcomes. Little is known, however, about the effect of fluoride at levels consistent with water fluoridation (i.e., 0.7 mg/L) on pregnancy and birth outcomes. We examined the relationship between maternal fluoride exposure, fertility, and birth outcomes in a Canadian pregnancy cohort living in areas where municipal drinking water fluoride concentrations ranged from 0.04 to 0.87 mg/L. Methods Using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) study, we estimated fluoride exposure during pregnancy using three different metrics: (1) maternal urinary fluoride concentrations standardized for specific gravity (MUFSG) and averaged across all three trimesters (N = 1566), (2) water fluoride concentration (N = 1370), and (3) fluoride intake based on self-reported consumption of water, coffee, and tea, adjusted for body weight (N = 1192). Data on fertility, birth weight, gestational age, preterm birth, and small-for-gestational age (SGA) were assessed. We used multiple linear regression to examine associations between fluoride exposure, birth weight and gestational age, and logistic regression to examine associations with fertility, preterm birth, and SGA, adjusted for relevant covariates. Results Median (IQR) MUFSG was 0.50 (0.33–0.76) mg/L, median water fluoride was 0.52 (0.17–0.64) mg/L, and median fluoride intake was 0.008 (0.003–0.013) mg/kg/day. MUFSG, water fluoride concentrations, and fluoride intake were not significantly associated with fertility, birth weight, gestational age, preterm birth, or SGA. Fetal sex did not modify any of the associations. Conclusion Fluoride exposure during pregnancy was not associated with fertility or birth outcomes in this Canadian cohort.
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