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Biomedical subjects

H W Baker

Publications and source records attributed to H W Baker.

At least 19 recordsLinked to original sources
PubMed2001

Feasibility of surveillance of changes in human fertility and semen quality.

There is concern that male fertility is declining, but this is difficult to study because few men volunteer for studies of semen quality, and recruitment bias may over-represent the subfertile. The Human Reproduction Programme of the World Health Organization developed a protocol for multicentre studies of fertility involving a questionnaire for pregnant women to obtain time to pregnancy (TTP): the number of menstrual cycles taken to conceive. Male characteristics and semen quality will be determined in a subset of the partners. Our aim was to validate the TTP questionnaire, and to examine potential recruitment bias and feasibility of conducting large-scale surveillance of fertility. The questionnaire was administered to 120 pregnant women (16-32 weeks). Validation included internal reliability by consistency of responses, test-re-test reliability by repeat administration (20 women) and accuracy by comparison of gestational age from first antenatal ultrasound and menstrual dates. Internal reliability was high. Agreement between categorical responses on re-testing was very good (k > 0.8). In both the re-test and gestational age analysis, differences in TTP of 1 cycle were found (standard deviation <0.25 cycles). In this small pilot study there was no evidence of recruitment bias. Response rates indicate the feasibility of surveillance of fertility in large maternity centres.

Adult↗
PubMed2001

Frequency of disordered zona pellucida (ZP)-induced acrosome reaction in infertile men with normal semen analysis and normal spermatozoa-ZP binding.

Results of zona pellucida (ZP)-induced acrosome reaction (AR) are reported for 186 normospermic men with unexplained infertility and compared with 34 normal fertile men and 54 patients with disordered ZP-induced AR (DZPIAR) diagnosed after failure of standard IVF. For each ZP-induced AR test, four oocytes that failed to fertilize in IVF were incubated for 2 h with 2x10(6)/ml motile spermatozoa. Spermatozoa tightly bound to the ZP were recovered by aspirating the oocytes with a pipette and the AR assessed using pisum sativum agglutinin labelled with fluorescein. The standard deviation of the difference was 5.2% for repeated tests for ZP-induced AR on different ejaculates from 54 men. The ranges for the ZP-induced AR were 3-98% for normospermic infertile men, 24-95% for fertile men and 0-16% for DZPIAR patients. In the normospermic group, there was a significant correlation between ZP-induced AR and sperm concentration (Spearman r = 0.238, P < 0.001). Using ZP-induced AR < or =16% as the threshold for diagnosis of DZPIAR, the frequency of this condition in normospermic infertile men would be 25%. Thus DZPIAR is common with normospermic idiopathic infertility and this condition should be diagnosed before assisted reproductive technology since it requires intracytoplasmic sperm injection.

Acrosome Reaction↗
PubMed2000

Efficacy and acceptability of testosterone implants, alone or in combination with a 5alpha-reductase inhibitor, for male hormonal contraception.

Testosterone (T) treatment suppresses serum gonadotropins and reduces sperm output sufficiently for contraceptive efficacy in approximately 70% of Caucasian men. In the remaining 30% of men, an increase in 5alpha-reductase activity may maintain testicular androgen activity, thus accounting for the failure of sperm suppression. The form of T therapy is a major consideration in the safety and acceptability of T-based contraception. As compared to T ester injections, T implants provide a more physiological serum T profile and fewer side effects, but have not yet been used in contraceptive efficacy studies. We have used T implants (800-1200 mg every 3 months) in 29 normal men for 3-16 months. T implants produced long-term suppression of sperm densities below 1 million/mL in approximately 70% of men without significant androgenic side effects. No pregnancies occurred in 214 months of exposure. In 16 men failing to suppress within 3 months of T 800 mg, no evidence of enhanced spermatogenic suppression was seen with the co-administration of the type 2 5alpha-reductase inhibitor, finasteride, for 3 months when compared to placebo. We conclude that: 1) T implants provide adequate spermatogenic suppression in approximately 70% of Caucasian men, a rate comparable to intramuscular T injections but with minimal side effects; and, 2) the inclusion of a type 2 5alpha-reductase inhibitor does not enhance spermatogenic suppression.

5-alpha Reductase Inhibitors↗
PubMed2000

Necrospermia and chronic spinal cord injury.

OBJECTIVE: To determine whether improvement in quality of semen over 4 consecutive days of electroejaculation in men with chronic spinal cord injury (SCI) was consistent with epididymal necrospermia. DESIGN: Prospective study of a random sample of men with SCI. SETTING: A southeastern Australian SCI management center in collaboration with the specialist andrology service of a university-based department of obstetrics and gynecology in a tertiary referral hospital. PATIENT(S): Nine men with chronic spinal cord injury. INTERVENTION(S): Semen samples were obtained by using electroejaculation, and testicular biopsy samples were obtained by using fine-needle tissue aspiration. MAIN OUTCOME MEASURE(S): Semen analysis was performed according to World Health Organization criteria. Testicular biopsy and electron microscopy were done by using standard techniques. RESULT(S): During up to 4 days of consecutive-day electroejaculation, sperm motility and viability in semen obtained from men with chronic SCI increased by an average of 23% on days 2 and 3. The severity of the degenerative changes and the numbers of spermatozoa affected on day 1 became less marked by day 4. The changes were not present in late spermatids obtained from testicular biopsies. CONCLUSION(S): The asthenospermia of chronic SCI is similar to epididymal necrospermia and can be improved by consecutive-day electroejaculation.

Adult↗
PubMed2000

Feasibility of surveillance of changes in human fertility and semen quality.

To show that male fertility is declining is not simple. Few men volunteer and recruitment bias may lead to over-representation of the subfertile. Semen analysis has errors arising from counting and poorly standardized criteria, which may be overcome by automation. Time to pregnancy (TTP)-the number of menstrual cycles taken to conceive-measures fertility and allows male recruitment bias to be estimated. We review automated measurement of sperm concentration, motility and morphology and present a preliminary report on a study to assess a retrospective TTP questionnaire, recruitment bias and feasibility for large-scale surveillance of fertility.

Feasibility Studies↗
PubMed2000

Management of male infertility.

The causes of infertility are known in a small proportion of patients, and only a few are treatable: gonadotrophin deficiency, genital tract obstruction, sperm autoimmunity, coital dysfunction and reversible effects of toxins, drugs or intercurrent illnesses. Other patients have reduced sperm quality or function that may be associated with previous testicular damage, varicocele or non-specific genital tract inflammation. No treatments have been proved to increase semen quality and fertility in this group; intracytoplasmic sperm injection is the most appropriate management if a natural pregnancy is unlikely to occur. Apart from the transmission of genetic and chromosomal disorders and a small increase in the number of sex chromosomal aneuploidies associated with severe spermatogenic defects, the risk of serious adverse effects in intracytoplasmic sperm injection offspring is low. The pathogenetic mechanisms of the most common forms of defective sperm production are unknown, which prevents the logical development of effective treatment.

Embryo Transfer↗
PubMed2000

Defective sperm-zona pellucida interaction: a major cause of failure of fertilization in clinical in-vitro fertilization.

Sperm-zona pellucida binding and penetration were assessed on the oocytes that failed to fertilize from couples with >/=3 oocytes treated by standard in-vitro fertilization (IVF). There were four groups: fertilization rate 0% (n = 369), 1-25% (n = 194), 26-50% (n = 81) and 51-95% (n = 100). Of the couples with zero fertilization rate 70% had </=5 spermatozoa bound per zona pellucida and 42% had no spermatozoa penetrating the zona pellucida of any oocyte. In contrast, in the 51-95% fertilization rate group, only 17% had </= 5 spermatozoa bound per zona pellucida and 6% had no spermatozoa penetrating the zona pellucida. There was a significantly higher frequency of poor sperm morphology (</= 5% normal) in couples with zero fertilization rate (36%) than in the fertilization rate group 51-95% (7%). Incubation of oocytes from 68 couples with zero fertilization rate and low sperm-zonae pellucidae binding with fertile donor spermatozoa resulted in normal sperm-zona pellucida binding and most zonae pellucidae being penetrated. In conclusion, defective sperm-zona pellucida interaction was the major cause for low fertilization rates in standard IVF. This was usually because of defects of the spermatozoa rather than defects of the oocytes. Sperm defects likely to cause failure of fertilization should be diagnosed before commencing IVF and the patients directed to intracytoplasmic sperm injection.

Female↗
PubMed2000

A pre-coital pill? A preliminary in vitro study.

The use of the progestogen-only pill as a 'pre-coital contraceptive' was tested by in vitro studies of sperm-mucus interaction. The results suggest that a single tablet of levonorgestrel 30 microg, or norethisterone 350 microg, was effective in preventing sperm migration in the cervical mucus about 12 hours later. This suggests that the progestogen-only pill may be effective as a 'morning before pill'.

Cervix Mucus↗
PubMed2000

Localisation of clusterin in normal human sperm by immunogold electron microscopy.

In the human male reproductive tract, two forms of clusterin have been detected: the conventional heterodimeric form and a novel acrosomal form. On human sperm the novel form of clusterin is present in the acrosomal region of acrosome intact sperm only. The aim of this study was to determine the site of localisation of the acrosomal form of clusterin using immunogold electron microscopy on normal human sperm. Using the E5 anticlusterin mAb and a preembedding technique, acrosomal clusterin was localised in the acrosomal contents. Immunogold particles were detected on ethanol fixed spermatozoa that were subjected to Triton X-100 permeabilisation treatment. These sperm had lost their plasmalemma and outer acrosomal membrane. Specific immunogold labeling was present over the surface mainly of the acrosomal contents exposed by the loss of the plasma-lemma and outer acrosomal membrane. Immunogold particles were also detected in the equatorial segment of the sperm. These data confirm that the acrosomal form of clusterin is associated with the contents of the acrosome.

Acrosome↗
PubMed2000

The human acrosome reaction.

We developed tests of sperm-oocyte interaction: sperm-zona binding, zona-induced acrosome reaction, spermzona penetration and sperm-oolemma binding, using oocytes which failed to fertilise in clinical in vitro fertilization (IVF). Although oocyte defects contribute to failure of sperm oocyte interaction, rarely are all oocytes from one woman affected. Low or zero fertilization in standard IVF was usually caused by sperm abnormalities. Poor sperm-zona pellucida binding was frequently associated with failure of standard IVF and obvious defects of sperm motility or morphology. The size and shape of the acrosome is particularly important for sperm binding to the oocyte. The proportion of acrosome intact sperm in the insemination medium was related to the IVF rate. Inducing the acrosome reaction with a calcium ionophore reduced sperm-zona binding. Blocking acrosome dispersal with an acrosin inhibitor prevented spermzona penetration. Sperm-zona penetration was even more highly related to IVF rates than was sperm-zona binding. Some patients had low or zero fertilization rates with standard IVF but normal sperm by conventional tests and normal sperm-zona binding. Few of their sperm underwent the acrosome reaction on the surface of the zona and none penetrated the zona. In contrast, fertilization and pregnancy rates were high with intracytoplasmic sperm injection. We call this condition defective zona pellucida induced acrosome reaction. Discovery of the nature of the abnormalities in the signal transduction and effector pathways of the human zona pellucida induced acrosome reaction should result in simpler tests and treatments for the patients and also provide new leads for contraceptive development.

Acrosome Reaction↗
PubMed1999

Comparison of human cervical mucus and artificial sperm penetration media.

The cervical mucus penetration tests aid research and determine the clinical importance of positive sperm antibody tests. Limited availability and variability of human cervical mucus have instigated the search for mucus substitutes for these tests. This study compares sperm migration in cervical mucus with that in artificial media including hyaluronate solution, egg white and albumin Tyrode solution. Results were quantified by measuring the migration distance (the maximum distance of capillary migration from a semen reservoir by spermatozoa after 1 h) and the sperm concentration at half the migration distance. The mean of both measures for cervical mucus and hyaluronate solution were equivalent [4.4 +/- 1.1 (SD) versus 4.3 +/- 1.0 cm and 118 +/- 51 versus 111 +/- 44x10(3)/ml], and higher than in egg white and albumin Tyrode solution. Antisperm antibodies impaired sperm penetration in cervical mucus and hyaluronate solution in a similar manner (r = 0.92). These results suggest that hyaluronate solution sufficiently resembles human cervical mucus in terms of penetrability that it may be used as a substitute for mucus in capillary tube tests of sperm function. The higher penetrability of cervical mucus and hyaluronate solution is probably related to a channelling effect due to their polymeric structure.

Albumins↗
PubMed1999

Efficacy and safety of recombinant human follicle stimulating hormone (Gonal-F) with urinary human chorionic gonadotrophin for induction of spermatogenesis and fertility in gonadotrophin-deficient men.

In order to evaluate the efficacy and safety of recombinant human follicle stimulating hormone (r-hFSH) in combination with urinary human chorionic gonadotrophin (HCG) to induce spermatogenesis and fertility in gonadotrophin-deficient men, we conducted a prospective, open, non-comparative multicentre study in two Australian academic medical centres. Ten men with gonadotrophin deficiency requiring induction of spermatogenesis and fertility were treated with HCG for 3-6 months followed by the s.c. self-administration of injections of r-hFSH in combination with HCG for 18 months. Among the eight men who commenced r-hFSH treatment, seven demonstrated sperm output at a median of 6 months and five achieved the target sperm output of 1. 5x10(6) per ml at a median of 9 months of FSH treatment. Mean testicular volume increased by 4.2 ml during FSH treatment. Three men produced pregnancies in their partners, two of which resulted in the birth of healthy babies and a third patient's partner had a miscarriage. We conclude that r-hFSH is well tolerated and effective in inducing testis growth, spermatogenesis and fertility in gonadotrophin-deficient men. The efficacy of r-hFSH seems comparable with urinary FSH at restoring normal fertility in gonadotrophin-deficient men.

Adolescent↗
PubMed1999

Chromosome translocations in couples with in-vitro fertilization implantation failure.

Recurrent miscarriage is known to be associated with parental chromosomal abnormalities, particularly balanced reciprocal and Robertsonian translocations. The aim of this study was to test the hypothesis that couples with in-vitro fertilization (IVF) implantation failure, like those with recurrent miscarriage, have a higher than expected prevalence of translocations which may impact on pregnancy outcome. Patients who previously had at least 10 embryos transferred without achieving clinical pregnancy were evaluated for chromosome abnormalities as part of screening investigations for implantation failure. Recurrent miscarriage patients with a history of at least three consecutive first-trimester abortions were also tested. Results were compared to reports of infertility patients presenting for treatment and population neonatal screening programmes. Chromosomal abnormalities overall were detected in 13/514 individuals with implantation failure (2.5%), and 15/319 individuals with recurrent miscarriage (4. 7%). Translocations (reciprocal and Robertsonian) were found in 7/514 individuals (1.4%) and 7/219 couples (3.2%) with implantation failure (P < 0.0005 compared with infertile controls and P < 0.0001 compared with screened neonates). Translocations were found in 13/319 individuals (4.1%) and 12/130 couples (9.2%) with recurrent miscarriage. Balanced parental translocations may be implicated in the pathogenesis of IVF-implantation failure. Genetic evaluation should be considered as part of the investigation of these patients.

Adult↗
PubMed1999

An important role of actin polymerization in the human zona pellucida-induced acrosome reaction.

The effects of inhibitors of actin polymerization and depolymerization, cytochalasins and phalloidin, on the human zona pellucida (ZP)-induced acrosome reaction (AR) were investigated. Motile spermatozoa, selected by swim-up technique from normozoospermic men, were incubated in medium with or without the actin modulators. Oocytes (four per test) which had failed to fertilize in vitro were added and incubation continued for 2 h. The spermatozoa bound to the ZP were dislodged by repeatedly aspirating the oocytes with a small-bore pipette and the status of the acrosomes was determined by fluorescein-labelled Pisum sativum agglutinin (PSA). Double immunofluorescent staining with PSA and an anti-actin monoclonal antibody illuminated the acrosomal region of acrosome-intact spermatozoa. In calcium ionophore-induced AR spermatozoa, actin staining was confined to the equatorial segment, post-acrosomal region and tail. Cytochalasins B and D significantly inhibited ZP-induced AR in a dose-dependent manner (P < 0.001). Both inhibitors had no effect on the acrosome of spermatozoa in the insemination medium. Cytochalasin B or D (10-40 micromol/l) had no effect on total percentage motile spermatozoa but decreased sperm velocity and hyperactivation. Phalloidin had no effect on the ZP-induced AR or sperm motility. In conclusion, actin polymerization plays an important role in human ZP-induced AR.

Acrosome Reaction↗
PubMed1998

Antibodies to beta2 glycoprotein I are associated with in vitro fertilization implantation failure as well as recurrent miscarriage: results of a prevalence study.

OBJECTIVE: To investigate whether antiphospholipid and related autoantibodies are associated with IVF implantation failure as well as with recurrent spontaneous miscarriage. DESIGN: Prevalence study. SETTING: University teaching hospital and associated IVF unit. PATIENT(S): Patients with at least three consecutive first-trimester miscarriages (n = 97), patients undergoing IVF who had at least 10 embryos transferred without any resulting clinical pregnancy (n = 105), fertile women (n = 106), and patients newly referred for IVF treatment (n = 52). INTERVENTION(S): Antibodies tested included lupus anticoagulant; immunoglobulin (Ig) G and IgM isotypes of each of anticardiolipin antibody, antiphosphatidylserine, antiphosphatidylethanolamine, and antiphosphatidylinositol; beta2 glycoprotein I antibodies; and antinuclear antibodies. Statistical analysis included chi2 and Fisher's exact tests for differences between groups, and multiple linear regression analysis and Spearman's nonparametric tests for relations between results. MAIN OUTCOME MEASURE(S): Seropositivity for autoantibodies tested. RESULT(S): Overall, 84 (23%) of the 360 samples tested positive for at least one autoantibody. Beta2 glycoprotein I IgM antibody and antinuclear antibody were significantly associated with both IVF implantation failure and recurrent miscarriage. CONCLUSION(S): Autoantibodies, particularly beta2 glycoprotein I antibodies and antinuclear antibodies, are associated with IVF implantation failure as well as with recurrent spontaneous abortion, although the mechanism is still unclear. The high seroprevalence of antibodies to beta2 glycoprotein I suggests that it may have an important role in autoimmune reproductive failure that needs to be explored further.

Abortion, Habitual↗
PubMed1998

Reproductive effects of nontesticular illness.

Diseases in other organs may impair the male reproductive system. Acute critical conditions such as severe trauma, surgery, myocardial infarction, burns, liver failure, intoxication, or starvation are associated with suppression of gonadotropin secretion and secondary hypogonadism. With chronic illnesses, a primary testicular disorder with elevated gonadotropin levels may occur. This may be associated with increased peripheral conversion of androgens to estrogens, resulting in clinical presentation of combined androgen deficiency and estrogen excess. The association of hypogonadism and feminization with cirrhosis of the liver is a classic example. Types of hypogonadism that may occur with chronic anemia, chronic renal failure, chronic spinal cord injury, thyroid diseases, Cushing's syndrome, diabetes mellitus, obesity, HIV infection, neoplasia, and other chronic illnesses are also described. Numerous drugs have side effects on the reproductive system.

Acute Disease↗