Human subfertility: explorative studies on some pathophysiologic factors in semen and follicular fluid.

Contains fulltext : 52284.pdf (publisher's version ) (Open Access)Subfertility is defined as failure to conceive after 1 year of regular, unprotected intercourse with the same partner. It is a prevalent disorder affecting 10-17% of all couples in the Western world. The WHO reports that in 20% of cases the cause of subfertility is originating from the male, and in 38% is mainly of female origin. In 27% fertility abnormalities are found in both partners. Although there are many known causes of subfertility, ranging from congenital, genetic, endocrine, infective and environmental factors, in up to 15% of couples the aetiology of subfertility remains unknown. Since involuntary childlessness is a heavy burden for most subfertile couples, many seek help in the form of in vitro fertilization or intracytoplasmic sperm injection to achieve pregnancy. Although these techniques have improved the treatment of subfertility, the success rate is still low (around 25%), and hardly any alternative treatment options exist. Moreover, these techniques are a symptomatic, rather than a causal treatment for subfertility. Targeted treatment and, possibly, prevention of subfertility is indicated. To that end we need more knowledge of the pathophysiology and the causal determinants of subfertility. Of particular interest are the environmental and lifestyle factors implicated in subfertility, because these can be targeted for curative or preventive measures. A significant but largely neglected lifestyle factor is nutrition, being a source of micronutrients, and exogeneous antioxidants. Also, several endogenously synthesized antioxidants are essential. Furthermore, it is hypothesized in literature that matrix degradation by the plasminogen activator system and vascularization induced by the vascular endothelial growth factor (VEGF) are causally involved in subfertility. Part I of this thesis focuses on the role of folic acid and zinc sulphate on sperm parameters, while Part II of this thesis discusses the role of antioxidants, the plasminogen activator system and VEGF.RU Radboud Universiteit Nijmegen, 08 februari 2007Promotor : Braat, D.D.M. Co-promotores : Steegers-Theunissen, R.P.M., Thomas, C.M.G.232 p

Seminal plasma annexin A5 concentration is not associated with male subfertility and cannot be influenced by folic acid and zinc sulfate treatment.

Contains fulltext : 49847.pdf (publisher's version ) (Open Access

[Recurrent miscarriage turns out to be lung cancer]

Item does not contain fulltextBACKGROUND: If a positive pregnancy test is followed by profuse vaginal bleeding, the diagnosis of miscarriage can generally be made. Sometimes, however, elevated hCG levels may be associated with a phantom pregnancy, which may be a paraneoplastic symptom. CASE DESCRIPTION: A 27-year-old woman was referred for a diagnosis after having experienced 3 consecutive miscarriages. The diagnostic workup could not identify an underlying cause. After 3 more biochemical miscarriages, the original diagnosis was called into question and extensive testing for ectopic hCG production was performed. It appeared that the false pregnancies were paraneoplastic symptoms of an hCG-producing non-small cell lung cancer. After a lobectomy, the hCG levels returned to normal and a spontaneous pregnancy and uncomplicated delivery followed. CONCLUSION: Phantom pregnancy as a paraneoplastic symptom is extremely rare, but should be considered in patients presenting with recurrent, non-objectifiable miscarriages. Careful documentation of the menstrual cycle is necessary for early detection of the condition. The fact is that vaginal bleeding after a positive pregnancy test can still be a normal menstruation

Influence of pesticides on male fertility.

Contains fulltext : 53221.pdf (publisher's version ) (Closed access)Several studies have shown a decline in human semen quality and increased risks of male subfertility. This paper provides an overview of the mechanisms of pesticide-induced reproductive toxicity and the effects on male fertility since exposure to pesticides may be one of the causes of these disorders. Pesticides may directly damage spermatozoa, alter Sertoli cell or Leydig cell function, or disrupt the endocrine function in any stage of hormonal regulation (hormone synthesis, release, storage, transport, and clearance; receptor recognition and binding; thyroid function; and the central nervous system). These mechanisms are described with respect to the effects of pesticide exposure in vitro and in vivo. In epidemiologic studies, effects on sperm quality and time to pregnancy are reviewed. Clear effects on male fertility have been demonstrated for some pesticides [eg, dibromochloropropane, ethylene dibromide]. But results from more recent studies are inconsistent, and no uniform conclusion can be drawn about the effects of pesticides on male reproduction

A genetic polymorphism and male fertility - Letter

Contains fulltext : 57276.pdf (publisher's version ) (Closed access

The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility.

Contains fulltext : 52107.pdf (publisher's version ) (Closed access)Current treatments of subfertile couples are usually empiric, as the true cause of subfertility often remains unknown. Therefore, we outline the role of nutritional and biochemical factors in reproduction and subfertility. A literature search was performed using MEDLINE, Science Direct and bibliographies of published work with both positive and negative results. The studies showed that folate has a role in spermatogenesis. In female reproduction, folate is also important for oocyte quality and maturation, implantation, placentation, fetal growth and organ development. Zinc has also been implicated in testicular development, sperm maturation and testosterone synthesis. In females, zinc plays a role in sexual development, ovulation and the menstrual cycle. Both folate and zinc have antioxidant properties that counteract reactive oxygen species (ROS). Thiols, such as glutathione, balance the levels of ROS produced by spermatozoa and influence DNA compaction and the stability and motility of spermatozoa. Oocyte maturation, ovulation, luteolysis and follicle atresia are also affected by ROS. After fertilization, glutathione is important for sperm nucleus decondensation and pronucleus formation. Folate, zinc, ROS and thiols affect apoptosis, which is important for sperm release, regulation of follicle atresia, degeneration of the corpus luteum and endometrial shedding. Therefore, the concentrations of these nutrients may have substantial effects on reproduction. In conclusion, nutritional and biochemical factors affect biological processes in male and female reproduction. Further research should identify pathways that may lead to improvements in care and treatment of subfertility

Review of the role of the plasminogen activator system and vascular endothelial growth factor in subfertility.

Contains fulltext : 71158.pdf (publisher's version ) (Closed access)OBJECTIVE: To assess the importance of the plasminogen activator (PA) system and vascular endothelial growth factor (VEGF) in subfertility. DESIGN: Review. SETTING: Two university IVF centers. INTERVENTION(S): Systematic literature search (MEDLINE, Science Direct, and bibliographies of published works). RESULT(S): The PA system in the male is involved in the passage of spermatozoa precursor cells over the blood-testis barrier, the epididymal maturation of spermatozoa, the modifications of the sperm surface for capacitation, the acrosome reaction and zona pellucida attachment, and finally the facilitation of spermatozoa to move into the fallopian tubes. In the female, the PA system plays a role during ovulation in the release of the oocyte from the follicle, the facilitation of oocyte movement into the fallopian tubes, and the extracellular matrix degradation important for angiogenesis in the ovary. The function of VEGF during fertilization is largely unknown. It has been suggested that VEGF is important for the fluid and proteins in semen and fluid secretion in the female genital tract, thereby influencing sperm motility and survival. The latter could be due to an effect of VEGF on testicular microvasculature, through which an adequate microenvironment for spermatogenesis is provided. In the female, VEGF is involved in the regulation of the cyclic ovarian angiogenesis, the development and/or selection of follicles, the accumulation of follicular fluid, and corpus luteum angiogenesis. CONCLUSION(S): The role of the PA system and VEGF in reproduction most likely is of great interest. However, much of the data are derived from experimental animal studies. So far, information on the importance of these systems in humans is scarcely investigated. Therefore, further research is required to elucidate the role of the PA system and VEGF in the pathogenesis and prevention of male and female subfertility. Eventually, this will contribute to the improvement of the diagnosis of subfertility and may possibly lead to targeted therapeutic management of subfertility

Possible role of the plasminogen activation system in human subfertility.

Contains fulltext : 52549.pdf (publisher's version ) (Closed access)OBJECTIVE: To correlate components of the plasminogen activator (PA) system with fertility outcome parameters in participants in an IVF/intracytoplasmic sperm injection (ICSI) procedure. DESIGN: Case-control study. SETTING: Outpatient clinic for IVF/ICSI treatment at the Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. PATIENT(S): One hundred and fifty-six couples undergoing an IVF/ICSI procedure. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), and t-PA-PAI-1 complex concentrations in the ejaculate, spermatozoa, and follicular fluid (FF). RESULT(S): Concentrations of t-PA were higher in spermatozoa of the male factor subfertility group (geometrical mean, 77.1 pg/million spermatozoa; 25th-75th percentiles, 31.8-211.2), compared to fertile men (geometrical mean, 1.91; 25th-75th percentiles, 0.74-5.79) and idiopathic subfertile men (geometrical mean, 3.14; 25th-75th percentiles, 0.97-9.97). Furthermore, the concentration of t-PA in spermatozoa was significantly associated with pregnancy (odds ratio [OR], 0.995). Likewise, a trend was shown for higher t-PA concentrations in the FF of women with fallopian-tube pathology (geometrical mean, 18.5 pg t-PA/mg protein; 25th-75th percentiles, 11.4-25.7) or endometriosis (geometrical mean, 18.8; 25th-75th percentiles, 11.4-27.1), compared to fertile women (geometrical mean, 14.3; 25th-75th percentiles, 10.3-17.6) and idiopathic subfertile women (geometrical mean, 13.9; 25th-75th percentiles, 9.5-17.8). Also, t-PA in FF is associated with the proportion of cleaved embryos (regression coefficient, 0.16). The concentrations of u-PA, PAI-1, and t-PA-PAI-1 complex were comparable between diagnostic subgroups in both men and women. CONCLUSION(S): The t-PA concentrations in spermatozoa and FF tend to be higher in human subfertility, and seem to be associated with some fertility outcome parameters

A Patient With a Low-grade Mucinous Neoplasm Involving the Ovary and Pseudomyxoma Peritonei Originating in an Isolated Intestinal Duplication

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C677T methylenetetrahydrofolate reductase polymorphism interferes with the effects of folic acid and zinc sulfate on sperm concentration.

OBJECTIVE: To determine the frequency of C677T methylenetetrahydrofolate reductase (MTHFR) polymorphism in fertile and subfertile males, and the MTHFR-dependent response of sperm concentration after folic acid and/or zinc sulfate intervention. DESIGN: Double-blind, placebo-controlled intervention study.Two outpatient fertility clinics and nine midwifery practices in The Netherlands. PATIENT(S): One hundred thirteen fertile and 77 subfertile males.Daily capsules of folic acid (5 mg) and/or zinc sulfate (66 mg), or placebo for 26 weeks. MAIN OUTCOME MEASURE(S): Prevalence of C677T MTHFR polymorphism and the response of sperm concentration related to MTHFR carriership after intervention treatment. RESULT(S): The C677T methylenetetrahydrofolate reductase genotypes were comparable in fertile and subfertile males. Independent of fertility state, sperm concentration significantly increased in wild-types after folic acid and zinc sulfate treatment only. Heterozygotes and homozygotes did not significantly benefit from either treatment. CONCLUSION(S):C677T methylenetetrahydrofolate reductase polymorphism is not a risk factor for male factor subfertility. In contrast to heterozygotes and homozygotes for C677T MTHFR polymorphism, sperm concentration in wild-types significantly improved after folic acid and zinc sulfate intervention. A stronger role of other folate genes on spermatogenesis is suggested