J Hall

Sig-Nurture, Guilford, England, United Kingdom

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Publications (14)38.87 Total impact

  • No preview · Article · Dec 2000 · International Journal of Gynecology & Obstetrics
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    ABSTRACT: To evaluate which gamma-aminobutyric acid (GABA) receptor mediates the stimulatory effects of this neurotransmitter on the human sperm acrosome reaction, and to examine the interaction of progesterone, a physiologic inducer of the acrosome reaction, with the GABA(A) receptor. Prospective study. A university clinic of andrology. Men with normal sperm analysis parameters. None. The acrosome reaction of motile spermatozoa. The acrosome reaction was stimulated by GABA in a dose-dependent manner. This effect was inhibited completely by bicuculline, a GABA(A) receptor antagonist, and only partially by saclofen, a GABA(B) receptor antagonist. Accordingly, muscimol, a GABA(A) receptor agonist, stimulated the acrosome reaction to the same extent as GABA, whereas baclofen, a GABA(B) receptor agonist, was less effective. Preincubation with progesterone followed by the addition of GABA resulted in a significant increase in the percentage of acrosome-reacted spermatozoa compared with progesterone alone. However, this increase was less than a simple addition of effects, suggesting that GABA and progesterone act through the same receptor and/or use the same mechanism of action. To test this hypothesis, the ability of progesterone to induce acrosome reaction was tested in the presence of bicuculline, which suppressed the stimulatory effects of progesterone. Given that the GABA(A) receptor is linked to the chloride channel, we tested whether picrotoxin, a blocker of this channel, could modulate the effects of progesterone or GABA. Picrotoxin completely suppressed the acrosome reaction induced by progesterone and only partially suppressed that caused by GABA. gamma-Aminobutyric acid stimulated the acrosome reaction in human spermatozoa, acting mainly through the GABA(A) receptor and to a lesser extent through the GABA(B) receptor. Progesterone interacted with the GABA(A) receptor to induce the acrosome reaction, and the functional integrity of the chloride channel was vital for this effect.
    Full-text · Article · Jun 1999 · Fertility and Sterility
  • S Hutchon · S Thornton · J Hall · M Bishop
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    ABSTRACT: To evaluate the pregnancy potential of frozen-thawed surgically retrieved epididymal sperm when used with intracytoplasmic sperm injection (ICSI). From August 1994 to January 1997, 20 thawed samples of sperm from 19 patients, surgically retrieved and frozen after percutaneous or open epididymal aspiration, were used for ICSI. The results were compared with those obtained using fresh sperm obtained at the same procedure. Of the specimens of surgically retrieved sperm which had been frozen, stored and thawed, 15 had sufficient motile sperm for use with ICSI. The fertilization, cleavage and pregnancy rates in those cycles were similar to the same couples' previous cycle using fresh sperm from the same collection and to the overall results in the NURTURE ICSI programme obtained with fresh epididymal sperm. Scrotal exploration for diagnostic testicular biopsy and/or reconstructive surgery without having access to sperm-freezing and storage facilities could represent a lost opportunity for the patient.
    No preview · Article · May 1998 · British Journal of Urology
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    ABSTRACT: Various compounds have been used in the attempt to improve sperm motility, including pentoxifylline (PF), a methylxanthine derivative. It has been postulated that PF, being a phosphodiesterase inhibitor, increases sperm kinematic parameters and the number of spermatozoa exhibiting hyperactivated motility by raising the intracellular content of cAMP, a molecule involved in the generation of sperm energy. However, it has not been clarified whether the biological effects of PF on sperm motility correlate with its ability to increase intracellular cAMP levels. To examine this relationship, the kinematic parameters, hyperactivation, and intracellular cAMP content were evaluated in motile spermatozoa, obtained by discontinuous Percoll gradient and swim-up from 21 normozoospermic semen samples, incubated without and with PF for 0, 1, 2, and 4 h. PF increased beat cross frequency after 1 and 2 h of incubation, curvilinear velocity and lateral head displacement (ALH) after 4 h, and hyperactivation after 1, 2, and 4 h, and decreased linearity (LIN) after 1 h of incubation. The intracellular cAMP content of spermatozoa incubated with PF increased at all time-points examined. Both intracellular cAMP content and increase in hyperactivation in response to PF decreased with the length of incubation. In the absence of PF, cAMP content was unchanged and was correlated significantly only with ALH and the percentage of spermatozoa with hyperactivated motility. Following incubation with PF, cAMP content correlated with hyperactivation and all sperm kinematic parameters, with the exception of LIN and straightness. These findings suggest that the beneficial effects of PF on sperm kinematic parameters and hyperactivation are related to its ability to increase intracellular cAMP content.
    Full-text · Article · May 1998 · Human Reproduction
  • Jenny Hall · Simon Fishel
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    ABSTRACT: The first observation that in vitro fertilization (IVF) was useful for treating oligozoospermia and oligoasthenozoospermia was reported by Fishel and Edwards in 1982. This was followed by a series of cases indicating the value of IVF in such cases. Conventional IVF has been modified and refined to achieve increased rates of conception in cases of male factor infertility. Methods such as high insemination concentration IVF for the treatment of teratozoospermia and microscopic IVF for the treatment of oligozoospermia have had some impact on fertilization and pregnancy rates; however, reports of success are varied. The recent advent of micromanipulation and, in particular, intracytoplasmic sperm injection (ICSI) has overshadowed the use of these modified IVF procedures. Because of the high fertilization and pregnancy rates achieved with ICSI, other micromanipulation techniques (subzonal insemination and partial zona dissection) have been abandoned; there have also been suggestions that other more conventional techniques, i.e. IVF, should also be abandoned and that ICSI become the sole technique for the treatment of infertility. The rapid increase in the number of centres using ICSI has led to extreme pressure for individual units to achieve high fertilization and pregnancy rates and there is a temptation to assign all patients to ICSI treatment. It is important that, in this highly competitive environment, new techniques are not applied haphazardly and reduced to the mere injection of gametes and achievement of pregnancy regardless of the cause of infertility. In his 1986 IVF--Historical Perspective, Fishel quoted Auguste Comte: 'to understand science it is necessary to know its history'. IVF has much recent history in animal and also human work. Although ICSI is the most significant therapeutic advance in male infertility treatment, its application to human IVF is only 4 years old, with a paucity of animal studies on which to rely. For this reason IVF still plays a very important role in the treatment of male factor infertility and should only be ruled out when it has failed previously or the number of available sperm is limited.
    No preview · Article · Jan 1998 · Baillière s Clinical Obstetrics and Gynaecology
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    ABSTRACT: This study was undertaken to evaluate the effects of gamma-aminobutyric acid (GABA) and GABAergic agonists and antagonists on sperm kinematic parameters and hyperactivation, evaluated by a computer-assisted semen analysis (CASA) system, and intracellular cAMP content in 22 normozoospermic semen samples. Because of the possible interaction of progesterone with the GABAA receptor, we also evaluated the effects of progesterone on these parameters. GABA increased beat cross frequency, curvilinear velocity (VCL), the percentage of spermatozoa moving with an average path velocity > 10 microns/s (active) and hyperactivation, and decreased linearity and straightness. Bicuculline, a GABAA receptor antagonist, antagonized the effects of GABA on all these parameters except the percentage of active spermatozoa. Muscimol, a GABAA receptor agonist, increased VCL, the percentage of active spermatozoa, and hyperactivation by about the same extent as GABA, suggesting the involvement of the GABAA receptor. However, the GABAB receptor also seems to mediate some of the effects of GABA, because baclofen, a selective agonist for this receptor, increased significantly the percentage of active spermatozoa and hyperactivation. The effect of baclofen on this latter parameter was, however, less pronounced than that obtained with GABA or muscimol. Progesterone had the same effects as GABA on sperm kinematic parameters and hyperactivation and the simultaneous presence of both compounds was not more effective than each single one. GABA and progesterone did not have any effect on intracellular cAMP content. In conclusion, GABA modulated sperm kinematic parameters and increased hyperactivation. These effects have the same magnitude of those produced by progesterone and seem to be mediated mainly by the GABAA receptor. We speculate that GABA may be a physiological regulator of sperm function.
    Full-text · Article · Oct 1996 · Molecular Human Reproduction
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    ABSTRACT: Utilizing real-time computer image analysis, individual spermatozoa were selected using microaspiration. Selection criteria were based on potential hyperactivation motility characteristics; the amplitude of lateral head displacement >7.5 μm, curvilinear velocity >70 μm/s and linearity of <30%. For this pilot study, 16 patients (eight in each group) were recruited. Using subzonal insemination (SUZI), up to five (mean = 4.4 ± 0.3) spermatozoa selected using computer-image sperm selection (CISS) were microinjected, or up to 15 (mean = 12.8 ± 1.3 SD) unselected spermatozoa. In the group which utilized CISS, 28 out of 49 (57%) oocytes were fertilized compared with 13 out of 52 (25%) utilizing conventional SUZI (P < 0.04); polyspermy was 20% (n = 10) and 2% (n = 1) respectively. CISS with SUZI showed increased efficiency in achieving fertilization and is a novel approach to studying individual sperm function in a sperm egg bioassay where gamete ratios are close to unity.
    No preview · Article · Jul 1995 · Human Reproduction

  • No preview · Article · Apr 1995 · Human Reproduction
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    ABSTRACT: The purpose of this study was to investigate firstly whether beta 1-integrin cell adhesion molecules are expressed by human spermatozoa, and secondly whether there is any relationship between the expression of beta 1-integrin cell adhesion molecules and the fertilizing ability of human spermatozoa in vitro. A total of 50 semen samples were examined. The samples were obtained from the male partners of couples undergoing in-vitro fertilization (IVF) for either unexplained, tubal or male factor infertility. A panel of six monoclonal antibodies against beta 1-integrin cell adhesion molecules and immunohistochemical techniques were used to identify the presence of these molecules on the spermatozoa. The percentage of spermatozoa showing strong immunolabelling with each monoclonal antibody was assessed in each sample. The relationship between these results and the aetiology of infertility and incidence of fertilization was examined. beta 1-Integrins, and primarily the ones with alpha 4-, alpha 5- and alpha 6-chains, were expressed by human spermatozoa. Compared with semen samples from unexplained or male factor infertility patients, samples from tubal infertility patients had a significantly higher (P < 0.05) percentage of spermatozoa expressing adhesion molecules. There was a positive correlation between the expression of alpha 4, alpha 5 and alpha 6 adhesion molecules and the fertilizing ability of spermatozoa. The positive correlation between the presence of certain beta 1-integrin cell adhesion molecules and the fertilizing ability of human spermatozoa suggests that integrins may be putative determinants in egg-sperm recognition and interaction.
    No preview · Article · Apr 1995 · Human Reproduction

  • No preview · Article · Jan 1995 · Molecular Human Reproduction
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    ABSTRACT: The use of high insemination concentration (HIC) for in vitro fertilization (IVF) was compared with intracytoplasmic sperm injection (ICSI) in cases of male factor infertility. Sibling oocytes (n = 252) from 24 patients were used, 123 for HIC and 129 for ICSI. Although the incidence of fertilization was decreased with HIC (48% v. 61%), this treatment was nevertheless a viable option for many patients, especially when ICSI was not available. However, there was a higher incidence of cytoplasmic fragmentation of embryos after HIC compared with ICSI (36% v. 10%, P = 0.003) and the outcome was significantly affected by the severity of teratozoospermia. Using a cut-off of 5% normal forms, the incidence of fertilization with HIC for the group with < 5% normal forms was 37% compared with 72% for the group with > 5% normal forms; there was also a significant decrease in cleavage rate (P = 0.05) and the number of regular embryos (P = 0.005), and an increase in cytoplasmic fragmentation (P = 0.006) in patients with < 5% normal forms. No distinction was made between cases of teratozoospermia when ICSI was used. The present study confirms the value of HIC as a first line treatment for male infertility, as long as ICSI remains significantly more expensive and concerns on safety are mooted. However, the use of sibling oocytes for ICSI is recommended, especially in cases with < 5% normal sperm morphology.
    No preview · Article · Jan 1995 · Reproduction Fertility and Development
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    ABSTRACT: Comprehension of the intricate complexities of sperm function is clearly crucial to the success of attempts to manipulate it for the purposes of assisted conception. This is particularly important when considering various procedures for microassisted fertilization since these bypass critical physiological events that are mandatory for normal fertilization, to varying degrees. Methylxanthine derivatives such as pentoxifylline are useful agents for the management of oligoasthenozoospermic patients. This is particularly so for procedures such as SUZI where adequate motility of spermatozoa injected into the perivitelline space is crucial for fusion with the vitelline membrane to achieve fertilization. The generation of minute concentrations of reactive oxygen species in vitro may prove to be a valuable technique in this respect, in the light of recent evidence for their involvement in capacitation and hyperactivation. Induction of the acrosome reaction by non-invasive, non-toxic agents should markedly improve success rates for microassisted fertilization. Acrosin appears to play a central role in this and, therefore, it would seem prudent to monitor levels of acrosin activity in samples of spermatozoa used in assisted conception procedures. With respect to microassisted fertilization, the potential to select recently acrosome-reacted spermatozoa coated by activated acrosin promises to be a major improvement. Current methods employed for determination of the fertilization potential of spermatozoa are clearly inadequate (Polansky and Lamb, 1988; Aitken, 1990). In fact, the prevailing evidence suggests that no single parameter of sperm function reflects this potential (Zaneveld and Jeyendran, 1988). Therefore, we have both a scientific and a moral responsibility to investigate these processes further. Subsequently, we should be in a position to identify individual gametes with the potential for fertilization and so utilize procedures that result in maximal fertilization rates with minimal risk of polyploidy or abnormality.
    No preview · Article · Apr 1994 · Baillière s Clinical Obstetrics and Gynaecology

  • No preview · Article · Dec 1993 · Human Reproduction
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    ABSTRACT: c1 Simon Fishel, NURTURE (Nottingham University Research & Treatment Unit in Reproduction), Department of Obstetrics & Gynaecology, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, UK.
    No preview · Article · Sep 1993 · Reproductive Medicine Review

Publication Stats

271 Citations
38.87 Total Impact Points


  • 1995
    • Sig-Nurture
      Guilford, England, United Kingdom
  • 1993
    • University of Nottingham
      • Division of Obstetrics and Gynaecology
      Nottingham, ENG, United Kingdom