Biochemical markers of placental dysfunction in assisted conception.

A possible mechanism for poor perinatal outcomes in singleton pregnancies conceived following assisted reproductive technologies (ART) and those conceived naturally following a period of infertility (>12 months) is thought to be placental dysfunction. This was investigated by measuring plasma concentrations of biochemical markers: (i) soluble fms-like tyrosine kinase1 (sFlt1); (ii) placental growth factor (PlGF); (iii) leptin; and (iv) plasminogen activator inhibitor 2 (PAI-2), serially at four antenatal time points. Baseline concentrations of each marker after delivery were also measured.

Is assisted reproduction associated with abnormal placentation?

Artificial reproductive technologies (ART) and conception following a period of untreated infertility (>1 year) are independently associated with increased pregnancy complications in both singleton and multiple pregnancies. It is unknown if placental dysfunction associated with macroscopic and/or microscopic histological discrepancies might explain some of these variances. Our aim was to compare the histopathology of placentae from singleton pregnancies belonging to 3 groups, as follows: conception as a result of ART; spontaneous conception (<1 year of trying); and conception following untreated infertility (>1 year).

Fetal habituation in assisted conception.

Background: Neurodevelopment outcomes of children conceived by Assisted Reproductive Technology (ART)have been the subject of much recent attention. To date there are no reports of neurodevelopmental performance before birth in this group.

Aims: To compare habituation (a measure of brain function) in fetuses conceived by assisted reproduction techniques (ART) with naturally conceived (NC) fetuses.

Spermatogenic and sperm quality differences in an experimental model of metabolic syndrome and hypogonadal hypogonadism.

The synergistic effect of the co-morbidities that comprise metabolic syndrome (MetS) is increasingly being recognised as an important contributor in the pathology of a broad spectrum of seemingly disparate conditions. However, in terms of male reproductive function, beyond erectile dysfunction, little is known about the influence of this cohort (collectively or separately) on spermatogenesis and sperm quality. The aims of this study were to assess the reproductive tract of a MetS animal model for detrimental changes, to determine whether a group of compounds (advanced glycation end products and their receptor) known to cause cell dysfunction and DNA damage was present and assess whether hypogonadotropic hypogonadism was the main contributing factor for the changes seen.

Male diabetes mellitus and assisted reproduction treatment outcome.

The long-held view that diabetes has little effect on male reproductive function has been challenged by findings that the condition influences fertility in numerous previously undetected ways. This retrospective chart review of 3000 couples determined the incidence of couples with a male diabetic seeking assisted reproduction treatment and assessed any relationship between male diabetes and IVF/intracytoplasmic sperm injection (ICSI) outcome. Eight (2.

The influence of type 1 diabetes mellitus on spermatogenic gene expression.

Routine semen analysis found no differences in diabetic men; however, mRNA profiles showed changes in the expression of genes involved in oxidative stress.

Are pregnancy rates compromised following embryo freezing to prevent OHSS?

Objective: To compare pregnancy rates with fresh and frozen embryo transfer in patients admitted to Royal Jubilee Maternity Service (RJMS), Belfast between January 1st 2004 and December 31st 2005 with ovarian hyperstimulation syndrome (OHSS).

Method: A retrospective analysis of all ART cycles (2,283) carried out in RJMS between January 1st 2004 and December 31st 2005 and of all patients admitted to RJMS within 3 weeks of assisted reproduction therapy (ART).

Results: The incidence of OHSS requiring admission was 2.

Sildenafil citrate (Viagra) impairs fertilization and early embryo development in mice.

Objective: To determine the effects of sildenafil citrate, a cyclic monophosphate-specific type 5 phosphodiesterase inhibitor known to affect sperm function, on fertilization and early embryo cleavage.

Design: This acute mammal study included male and female mice assigned randomly, the females sacrificed after mating and their oocytes/embryos evaluated at four time periods after treatment.

Setting: Academic research environment.

Distribution of the receptor for advanced glycation end products in the human male reproductive tract: prevalence in men with diabetes mellitus.

Background: Diabetics have a significantly higher percentage of sperm with nuclear DNA (nDNA) fragmentation and increased levels of advanced glycation end products (AGEs), in their testis, epididymis and sperm. As the receptor for AGEs (RAGE) is important to oxidative stress and cell dysfunction, we hypothesise, that it may be involved in sperm nDNA damage.

Methods: Immunohistochemistry was performed to determine the presence of RAGE in the human testis and epididymis.

Sildenafil citrate improves sperm motility but causes a premature acrosome reaction in vitro.

Objective: To determine whether sildenafil citrate, a cyclic monophosphate-specific type 5 phosphodiesterase inhibitor, influences sperm motility or the acrosome reaction.

Design: Laboratory analysis of sperm motility after exposure to sildenafil citrate using computer-assisted semen analysis and acrosome reaction by fluorescein isothiocyanate-labeled peanut agglutinin staining.

Setting: An assisted reproductive technology (ART) unit.

Reduced sperm yield from testicular biopsies of vasectomized men is due to increased apoptosis.

Objective: To compare sperm yields, apoptotic indices, and sperm DNA fragmentation from vasectomized men and fertile men undergoing vasectomy.

Design: Testicular biopsies from vasectomized (n = 26) and fertile men (n = 46), were milked to calculate sperm/gram and also formalin-fixed to determine the numbers of developing sperm and incidence and intensities of testicular FasL, Fas, Bax, and Bcl-2. Testicular sperm DNA fragmentation was assessed using the alkaline Comet assay.

Effects of delta-9-tetrahydrocannabinol, the primary psychoactive cannabinoid in marijuana, on human sperm function in vitro.

Objective: To investigate effects of delta-9-tetrahydrocannabinol (THC) on human sperm function in vitro.

Design: Laboratory analysis of sperm motility after exposure to THC using computer-assisted semen analysis and acrosome reaction by fluoroscein isothiocyanate-labeled peanut agglutinin staining.

Setting: An assisted reproductive technology unit.

Dietary oestrogens and male fertility potential.

Reports of increased incidences of male reproductive abnormalities and falling sperm counts have prompted interest into the nature of these threats to global fertility. Xenoestrogens have been flagged as major culprits but to date, little is known about the effects of dietary phytoestrogens on male reproductive health. These non-steroidal oestrogens of plant origin are potent endocrine disruptors that modulate normal physiological functions.

Effects of short and long incubations on DNA fragmentation of testicular sperm.

DNA fragmentation in testicular sperm from men with obstructive azoospermia is increased by 4-hour and 24-hour incubations and after cryopreservation with the effect is intensified by post-thaw incubation. Testicular sperm for use in intracytoplasmic sperm injection (ICSI) should be injected without delay.

Soluble vascular endothelial growth factor receptor-1 (sFlt-1) is increased throughout gestation in patients who have preeclampsia develop.

Objective: This study was undertaken to analyze prospectively circulating vascular endothelial growth factor (VEGF) and its soluble receptor, (s) Flt-1, throughout normotensive and preeclamptic pregnancies and to assess the importance of these proteins in the development of preeclampsia.

Study Design: In this longitudinal cohort study, serum samples were collected from recruited subjects throughout pregnancy at 12, 20, 30, and 37 weeks and in the 24 hours before and after delivery. Subjects were divided retrospectively into normotensive and preeclamptic groups.

Vulvodynia.

Context: Vulvodynia is a term used to describe chronic burning and/or pain in the vulva without objective physical findings to explain the symptoms. The terminology and classification of vulvodynia continue to evolve, and much remains to be understood about the prevalence, pathogenesis, natural history, and management of this distressing condition.

Starting Point: James Aikens and colleagues showed that chronic vulval pain (vulvodynia or vulvar dysaesthesia) is associated with worse depressive symptoms (Am J Obstet Gynecol 2003; 189: 462-66).

Incidence of Fas positivity and deoxyribonucleic acid double-stranded breaks in human ejaculated sperm.

Objective: To determine the incidence of Fas positivity and DNA double-strand breaks (DSB) as indicators of early- and late-stage apoptosis in ejaculated sperm.

Design: Fas positivity was assessed by flow cytometry and DSB by the neutral Comet assay.

Setting: Andrology Laboratory, Royal Maternity Hospital, Belfast, Northern Ireland, United Kingdom.

Effects of cryopreservation on testicular sperm nuclear DNA fragmentation and its relationship with assisted conception outcome following ICSI with testicular spermatozoa.

The objective of the study was to investigate the effects of freeze-thawing on testicular sperm DNA fragmentation, fertilization rates and pregnancy rates following intracytoplasmic sperm injection with testicular spermatozoa (TESE). This ongoing prospective study included 88 couples attending for infertility treatment where the man presented with obstructive azoospermia at the Regional Fertility Centre, Belfast, UK. Patients were allocated to receive TESE treatment with fresh or freeze-thawed spermatozoa.

The hidden impact of diabetes on male sexual dysfunction and fertility.

Diabetes affects an increasingly large number of young men of reproductive age. Erectile and ejaculatory difficulties arise due to vascular and neuropathic problems. The treatment of these may have effects on fertility potential.

Chromogranin A proteolysis to generate beta-granin and WE-14 in the adenohypophysis during the rat oestrous cycle.

Immunohistochemical analysis of the male and female rat adenohypophysis revealed that chromogranin A (CgA), beta-granin and WE-14 immunostaining was localised to follicle stimulating hormone (FSH) producing cells, while luteinizing hormone (LH) producing cells exhibited chromogranin A and beta-granin immunostaining. The intensity of chromogranin A, beta-granin and WE-14 immunostaining exhibited variation during the oestrous cycle; weak immunostaining was observed during proestrous and oestrous, corresponding with the lowest cellular concentration of luteinizing and follicle stimulating hormone. Chromogranin A and beta-granin immunostaining were similar in both the male and female (at dioestrous), however, a larger number of more intense WE-14 immunopositive cells were evident in the male adenohypophysis relative to the female at any stage of the cycle.

Preventing ovarian hyperstimulation syndrome by inhibiting the effects of vascular endothelial growth factor.

Objective: To evaluate whether inhibiting the effects of vascular endothelial growth factor can prevent the ovarian hyperstimulation syndrome.

Study Design: Rates were hyperstimulated with follicle-stimulating hormone injections. On the final day of stimulation, the rats were randomized to receive or not receive exogenous soluble fmslike tyrosine kinase (sFlt-1).

Differences in mitochondrial and nuclear DNA status of high-density and low-density sperm fractions after density centrifugation preparation.

Objective: To determine the mitochondrial DNA and nuclear DNA fragmentation of sperm populations separated by using discontinuous density gradient.

Design: Analysis of mitochondrial and nuclear DNA status of sperm from high and low density layers.

Setting: Regional fertility center.

Variations in serum vascular endothelial growth factor binding profiles and the development of ovarian hyperstimulation syndrome.

Objective: To compare the ability of serum to sequester vascular endothelial growth factor (VEGF) among patients who did and did not develop ovarian hyperstimulation syndrome (OHSS).

Design: Prospective, observational study.

Setting: A regional fertility centre with a commitment to research.

Ovarian hyperstimulation syndrome and assisted reproductive technologies: why some and not others?

Background: alpha(2)-Macroglobulin (alpha(2)M) is a multifactorial binding protein, found in follicular fluid, that is a naturally occurring inhibitor of vascular endothelial growth factor (VEGF). The aim of this study was to determine if there is a relationship between serum VEGF levels, alpha(2)M levels and the development of OHSS in hyperstimulated subjects undergoing IVF (those with 15 or more oocytes).

Methods: Venous blood was collected at the time of oocyte retrieval from subjects who yielded 15 or more oocytes.