Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Introduction: In recent years, the average age of first reproduction has risen significantly, the mean now standing at around 30 years in many countries. The adverse effects of maternal age on fertility and reproduction have been well documented. However, the influence of paternal age on fertility, reproduction and postnatal health is relatively poorly understood, and 50% of all male infertility cases are classed as idiopathic or unexplained infertility. Methods: The aim of this study was to investigate factors that contribute to male infertility, split into two main parts. The first part focused on analysing data collected from patients who had undergone fertility treatment to assess the influence of different factors on infertility, especially at the genome level. The second part attempted to deal with some of the technical challenges of screening and diagnostic methods to study the genome, with the aim of providing tools that would assist future studies in pinpointing genetic factors responsible for infertility, especially in cases of idiopathic infertility. Results: Based on data from the first part of the study, it was determined that advanced paternal age can affect sperm progressive motility, sperm DNA integrity and the fertilisation rate of in vitro fertilisation (IVF) cycles, as well as the development of embryos. Direct analysis of sperm DNA fragmentation (SDF) and degradation levels revealed an association between elevated SDF and impaired embryo development. Furthermore, a correlation was shown between chromosome aneuploidy and variance in SDF and sperm DNA degradation. Moreover, aneuploidy can influence abnormal sperm morphology and consequently also progressive motility. Also, embryo development rate of IVF cycles on day three, demonstrated a significant decline in cycles where the sperm used for fertilisation had a high aneuploidy rate, which can highlight the reduced developmental capacity of aneuploid embryos. From the lifestyle factors assessed, only alcohol consumption significantly correlated with the sperm DNA damage. Therefore, poor semen quality may highlight damage that has been incurred by the sperm DNA. When the semen quality is suboptimal, the intracytoplasmic sperm injection (ICSI) technique is suggested as a standard strategy to improve the prognosis of ART. However, when the progressive motility is poor, the ICSI approach is not as effective. Based on our findings and in line with other studies, the only sperm parameter that can be affected by paternal age is sperm motility, which could be an indicator of SDF. Therefore, the decline in ICSI fertilisation rate in patients with impaired sperm progressive motility could be due to sperm DNA damage, and even ICSI cannot improve the fertilisation rate considerably. Discussion: The aim of the second part of this project was to establish a robust workflow for whole- genome amplification (WGA) and whole-genome sequencing of single cells to improve the coverage rate and fidelity, with the aim of providing means of detecting any mutation in the genome that might be responsible for reduced embryonic developmental competence. Towards this end, the efficiencies of two different WGA protocols (REPLI-g and TruePrime) were compared. Multiple technical factors required optimisation in order to create a suitable protocol. Our results demonstrated the overall superiority of REPLI-g compared to TruePrime in almost all the assessed parameters. The amplification rate of REPLI-g was much faster than that of TruePrime, and prolonged incubation led to overamplification and an increased duplication rate. However, the TruePrime method has a slower amplification rate and therefore, by increasing the incubation time, it was possible to improve the quality of the data. The modified protocol with reduced volume also had the most promising outcome in terms of the data produced, and could fulfil our expectations by being fast, cost-effective and efficient. Conclusion: In conclusion, the results from the first part of this study confirmed the negative impact of male age on assisted reproductive treatments, which can result in decreased success rates of fertilisation. Other factors such as sperm DNA damage may also contribute to this age effect, suggesting that assessing this parameter prior to fertility treatment, and attempting to mitigate elevated levels of sperm DNA damage, may be of value to older patients. Additionally, overcoming the technical challenges in studying genetic contributory factors in infertility is a promising step toward better understanding of the mutations and variations that are involved in this phenomenon.

The study explored the narratives of three adoptive couples. The participants were selected using criterion based convenience and snowball sampling. The adoptive couples’ data was captured through written narratives and/or individual or joint semi-structured interviews. The data was then analysed by means of thematic analysis conducted from the perspective of second order cybernetics. The results note the participants’ experiences of their infertility threatened their functioning as a couple. However, this threat to the couples’ functioning was limited by the adoptions through two means. First, the adoptions limited the couples’ communication about their infertility. Second, the adoptions allowed the couples to continue functioning as a couple dedicated to the goal of becoming parents. Differences between the participant couples’ experiences surrounded their interactions with social workers; their selection of support structures; their interaction with external systems; as well as their anxiety towards the individuation of the adopted child. / Psychology / M.A. (Clinical Psychology)

Thesis advisor: Barbara E. Wolfe / Studies suggest that eating disorder (ED) pathology may be linked to ovulatory and unexplained infertility in women who present to reproductive treatment centers. Specifically, studies have linked hypothalamic amenorrhea, oligomenorrhea, and anovulatory cycles to disordered eating. Advances in Assisted Reproductive Technology can lead to successful conception for women with ED; however, they have a higher risk for poor maternal and fetal outcomes. This descriptive, comparative, quantitative study examined disordered eating and psychological symptoms in women with ovulatory and unexplained infertility compared with women receiving routine health care from their primary care providers. Women ages 20 to 44 were recruited. After providing verbal consent, a study packet was mailed to the study participant's home. The Eating Disorder Inventory-3-Referral Form and Herman and Polivy Restraint Scale measured disordered eating symptoms. The Speilberger Anxiety Inventory and Beck Depression Inventory-II examined psychological symptoms. Provisional DSM IV TR diagnoses were ascertained using the Eating Disorder Inventory-3-Symptom Checklist, along with other scale items. Multivariate analysis of covariance (MANCOVA) confirmed that women with ovulatory and unexplained infertility had significantly higher Desire for Thinness (p = .001) and Bulimia (p = .007) subscale scores putting them at risk for Anorexia Nervosa or Bulimia. Women receiving routine care had significantly higher Body Dissatisfaction (p = .000) subscale scores consistent with their higher weight and tendency toward overeating. Women receiving routine care also had significantly higher Restraint (p = .000) scale scores, leaving them at risk for dietary disinhibition. The groups did not differ on psychological symptoms. Women with infertility had lifetime ED diagnoses many times the national ED prevalence rate, similar to the research findings of Freizinger et al. (2010). The study results support that women with ovulatory and unexplained infertility are at risk for having an occult ED. The critical import of integrating ED assessment into infertility evaluation, reproductive and primary care was implicated. Further study to isolate biobehavioral markers to better identify women at risk for ED and improve their maternal and fetal outcomes was recommended. / Thesis (PhD) — Boston College, 2010. / Submitted to: Boston College. Connell School of Nursing. / Discipline: Nursing.

This controlled descriptive study was designed to investigate the psychological status of couples who are engaged in advanced fertility treatments. A battery of psychological test instruments, including the Millon Behavioral Health Inventory (MBHI), the Health Attribution Test (HAT), the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), and the Marlowe-Crowne Social Desirability Scale (MCSDS), was used to measure psychological variables that have been shown in the infertility research literature to be associated with the psychological experiences of infertility patients. The scores from the four assessment instruments were compared with those of pregnant couples in childbirth education classes to differentiate the impact of stress associated with fertility treatment from the stress experienced by third trimester pregnant couples. Eighty-five subjects (42 male and 43 female) volunteered for the study and completed packets of questionnaires. The groups were designated Treatment (infertile couples) and Control (pregnant couples). The resulting data were collected and analyzed on the basis of group mean scores on the test instruments.

Thesis (M.Sc. (Medical Sciences)) -- University of Limpopo, 2021 / Infertility, defined as the inability to conceive following one year of unprotected sexual intercourse, respectively affects 25% of couples globally. Oxidative stress (OS) has been greatly related to the idiopathic cause of infertility and Camellia sinensis contains antioxidants that may enhance reproductive functions. This study focussed on the effects of Camellia sinensis (green and black tea) on human sperm functions in both normal and abnormal samples. Semen samples (n= 59) collected from donors were liquefied, analysed, and classified as normal (n=40) and abnormal (n= 19) using the WHO criteria. Samples were washed and exposed to aqueous leaf extracts of green and black tea (0, 0.4, 4, 40, 405 μg/ml) for 1 hour. Human Tubular Fluid (HTF) served as the control. The respective sperm parameters were analysed (sperm motility, vitality, DNA fragmentation, mitochondrial membrane potential (MMP), capacitation and acrosome reaction (CTC) and reactive oxygen species (ROS). Green and black tea significantly increased vitality, and intact MMP, while it significantly reduced, CTC, and intracellular ROS as well as DNA fragmented spermatozoa in both normal and abnormal samples compared to the control (p<0.05). A significant increase in sperm CTC, ROS, with a decrease in sperm vitality, and intact MMP was observed in the abnormal compared to the normal samples (p<0.05). No significant change in motility was observed between normal and abnormal samples compared to their respective controls, in both green and black tea (p>0.05). Camellia sinensis improved human sperm function in vitro and may be attributed to its antioxidant activity. / National Research Foundation (NRF)

The significance of ultrasound examination in the management of experimental uterine transplantation Abstract Uterine transplantation (UTx) represents a new experimental method of treatment of absolute uterine factor infertility (AUFI), which includes inability to conceive and deliver as a result of absence of the uterus. This can be congenital (Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS)) or acquired (after hysterectomy, severe congenital uterine malformations). For a woman affected this way is the uterine transplantation the only way to give birth to a child by herself. This is a very sophisticated and invasive procedure for the treatment of sterility with promising results, but the woman - recipient of the uterus - is burdened by at least three abdominal surgeries (transplantation, Caesarean section, explantation), in vitro fertilization and by the need to use immunosuppressive therapy. The dissertation summarizes current knowledge on this issue from the perspective of a gynecologist-obstetrician, who regularly examined by ultrasound or gynecologically participants in the Czech uterine transplant study in 2016-2019, which was carried out on the basis of a cooperation agreement between two Prague hospitals - IKEM and FN Motol. The set contains data on ten patients with a transplanted uterus, five from...

Bakgrund: Infertilitet är ett sjukdomstillstånd som innebär att ett par inte kan uppnå en klinisk graviditet under mer än ett år av försök. Det är mellan 10-15 % av alla par i fertil ålder som drabbas av tillståndet i varje land. Orsaken som hittas i 90 procent av fallen är antingen manliga, kvinnliga eller gemensamma faktorer. När ingen orsak hittas kallas det för oförklarlig-, eller idiopatisk infertilitet. Innan diagnostisering och eventuell behandling utförs därför noga utredningar med analyser på både kvinnan och mannen. Behandlingen bestäms därefter utifrån orsak. Vid kvinnlig infertilitet är in vitro-fertilisering (IVF) den mest vanliga icke-farmakologiska proceduren som används framför allt vid oförklarlig infertilitet och åldersfaktorer. Antiöstrogenet klomifencitrat har i många decennier varit farmakologiska förstahandsbehandlingen vid anovulatorisk infertilitet men vid de senaste 10 åren har den ersätts med aromatashämmaren letrozol som med en liknande mekanism kunnat ge upphov till ovulationsstimulering. Syfte: Syftet med examensarbetet var att utvärdera och jämföra effekterna av antiöstrogenet klomifencitrat med aromatashämmaren letrozol vid infertilitetsbehandling hos kvinnor. Metod: För att uppnå syftet utfördes litteratursökningar av relaterade vetenskapliga studier i den medicinska databasen PubMed. Nyckelorden som användes vid sökning var “female infertility”, “clomiphene” och “letrozole” och därefter hämtades fem randomiserade kontrollerade vetenskapliga artiklar (RCT) som granskades i resultatdelen av arbetet. Resultat: Samtliga studier, utom studie 5, visade att aromatashämmaren letrozol hade bättre effekt på ovulationstimuleringen och därmed också att uppnå klinisk graviditet än vad klomifencitrat hade. Administrering av letrozol ledde också till större tjocklek av endometrium och fler antalet mogna folliklar. Å andra sidan visade sig letrozol ge högre sannolikhet till multipla graviditet i studie 5. Det förekom ett par fall av allvarliga biverkningar under administrering av samtliga läkemedel, dock var majoriteten av biverkningarna milda och förekom i form utav huvudvärk, illamående, gastrointestinala besvär, trötthet och värmevallningar. Slutsats: Resultaten tyder på att letrozol är ett mer effektivt alternativ till infertilitetsbehandling av kvinnor. Eftersom den dessutom har mycket lägre halveringstid än klomifencitrat gör den mer säker att använda då det låg östrogennivå är ej optimal hos kvinnor i fertil ålder. / Background: Infertility is a condition that is based on a couple not being able to achieve a clinical pregnancy for more than a year of trying. Between 10-15 % of all heterosexual couples of childbearing age are affected by the condition in each country. The cause that is found in 90 percent of cases is either male-, female- or common factors. When no cause is found, it is called unexplained or idiopathic infertility. Before diagnosis and possible treatment, careful investigations are therefore performed with analysis on both the woman and the man. The treatment is then determined based on the cause. In female infertility, in vitro fertilization (IVF) is the most common non-pharmacological procedure used primarily for unexplained infertility and age factors. The antiestrogen clomiphene citrate has for many decades been the first-line parmacological treatment for anovulatory infertility, but in the last 10 years it has been replaced by the aromatase inhibitor letrozole, which with a similar mechanism have effect on ovulation stimulation. Aim: The aim of this thesis was to evaluate and compare the treatment effects of the antiestrogen clomiphene citrate with the aromatase inhibitor letrozole in female infertility. Method: A literature search of related scientific studies was implemented in the medical database PubMed. The keywords used in the searchfield were ”female infertility”, ”clomiphene” and ”letrozole” and then five randomized controlled trial articles (RCT) were selected to be reviewed in the results part of the thesis. Results: All studies, except for study 5, showed that the aromatase inhibitor letrozole had a better effect than clomiphene citrate on ovulation stimulation and thus also to achieve a clinical pregnancy. Administration of letrozole also led to greater endometrial thickness and increased numer of mature follicles. In study 5 on the other hand, letrozole was shown to increase the likelihood of multiple pregnancies. There were a couple of cases of serious side effects during the administration of these drugs, however, the majority of the side effects were mild and occured in the form of headaches, nausea, gastrointestinal disorders, fattigue, and hot flashes. Conclusion: In conclusion, the results suggest that letrozole is a more effective alternative to infertility treatment for women. In addition, since it has a much lower half-life than clomiphene citrate, it is safer to use as low estrogen levels are not optimal in women of childbearing potential.

Call number: LD2668 .T4 1936 S21