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Biomedical subjects

M G Hull

Publications and source records attributed to M G Hull.

At least 37 records · Page 2Linked to original sources
PubMed1997

Ovarian dysfunction in endometriosis-associated and unexplained infertility.

PURPOSE: The impact of endometriosis and unexplained infertility on follicular function and fertilization of oocytes in cycles totally unperturbed by exogenous gonadotrophins, when compared with controls with tubal damage, were examined. METHODS: In natural cycles, without any exogenous gonadotropins, endocrine and ultrasonographic studies of follicular maturation in 18 women with minor endometriosis (41 cycles), 15 women with unexplained infertility (31 cycles), and 34 women with tubal damage (88 cycles) were performed. RESULTS: The endometriosis group had a significantly longer follicular phase (median: 15, 13, and 13 days). Both endometriosis and unexplained infertility had significantly reduced LH concentrations in follicular fluid compared with tubal damage (median: 12.1, 11.5, and 15.9 IU/L, respectively). Endometriosis was associated with a significantly reduced fertilization rate compared with unexplained infertility or tubal damage (46, 65, and 69%, respectively). CONCLUSIONS: These data show continuing evidence of ovulatory dysfunction leading to reduced fertilization rates in women with minor endometriosis.

Adult↗
PubMed1997

Is the outcome of in-vitro fertilization and embryo transfer treatment improved by spontaneous or surgical drainage of a hydrosalpinx?

A pilot study was designed to examine whether the outcome of embryo transfer in women with a hydrosalpinx might be improved by surgical drainage of the hydrosalpinx at the time of oocyte collection for in-vitro fertilization treatment. A comparative, controlled but retrospective analysis of the results was performed of all women with infective tubal damage aged <40 years old, who had ovulatory cycles, a normal uterus and a partner with normal spermatozoa. A standardized treatment regimen was used. A maximum of three embryos were transferred. Hydrosalpinx was defined by prior hysterosalpingography and/or laparoscopy with transcervical dye injection. A total of 237 embryo transfer cycles in women with hydrosalpinges (tubal distension not visible in 151, visible but not drained in 30 and drained in 56) were compared with 705 embryo transfer cycles in women with tubal disease but no hydrosalpinx. Results were analysed in the first three cycles but also separately in the first cycle to check for bias. Success rates were higher in the first cycle, but did not significantly influence overall differences. Implantation rates were significantly reduced overall in the hydrosalpinx group (8.0 versus 13.2% for controls; P < 0.001), being 8.3% (P < 0.01) in the subgroup without evident tubal distension and 7.5% (not significant) in the drained hydrosalpinx group. This study shows that tubal damage with distal occlusion is associated with a marked reduction in embryo implantation, even in the absence of obvious fluid distension. Surgical drainage of distended hydrosalpinges appears to offer no benefit.

Adult↗
PubMed1996

Relative bioactivity of endogenous luteinizing hormone during superovulation therapy for in vitro fertilization in normal-cycling women.

PURPOSE: Impaired outcome of in vitro fertilization treatment has been related to abnormal luteining hormone (LH) secretion and to the occurrence of a premature LH surge. The purpose of this study was to compare LH serum concentrations, measured by bioassay (LH-b) and immunoassay (LH-i), during early and late follicular phases in normal-ovulatory women who were stimulated with clomiphene, human menopausal gonadotropin (HMG), and human chorionic gonadotropin (hCG), while undergoing in vitro fertilization (IVF) treatment for infertility, due mainly to tubal damage. RESULTS: Of 22 patients, 15 had an LH surge (surge group) before receiving hCG and 7 did not (nonsurge group). LH-b and LH-i concentrations were higher in the late follicular phase than before clomiphene treatment, but the LH-b/LH-i (B/I) ratios remained unchanged and there were no significant differences between the LH surge and the nonsurge groups. In the surge group, the B/I ratio appeared to fall during the LH surge [presurge values, 5.4 +/- 0.5 (SD) and 5.2 +/- 0.5; surge values, 4.9 +/- 0.6 and later 4.0 +/- 0.6], but the differences were not significant, and in some individuals, the B/I ratio later rose as the LH surge progressed. CONCLUSIONS: Our findings suggest that interference with IVF outcome by a spontaneous LH surge is due to quantitative and/or exposure time effects on the oocyte, rather than to any qualitative variation in bioactivity of LH.

Adult↗
PubMed1996

The age-related decline in female fecundity: a quantitative controlled study of implanting capacity and survival of individual embryos after in vitro fertilization.

OBJECTIVE: To determine strictly comparable rates per embryo of implantation and birth of a baby related to the woman's age, which would be representative of natural fertility at least in relative terms. DESIGN: Comparative study of IVF-ET results controlling for confounding variables including cause and duration of infertility, history of previous pregnancy, hormonal treatment, rank cycle of treatment, and numbers of embryos transferred and available. SETTING: University comprehensive fertility service. PATIENTS: All couples (n = 561) in their first cycle of treatment reaching oocyte collection, women with normal uterus and ovulatory cycles, and men with normal sperm. INTERVENTIONS: Standardized methods of pituitary desensitization, ovarian stimulation, and IVF-ET, and maximum of three embryos transferred. MAIN OUTCOME MEASURES: Oocytes, pregnancies, and live births per cycle; fertilization and cleavage rates; embryo implantation and live baby rates. RESULTS: The numbers of oocytes and consequent embryos declined with age but fertilization and cleavage rates rose slightly. Embryo implantation rates were reduced when no more than three embryos were available (9.3 percent), especially in women aged 35 to 39 years (6.2 percent) or older compared with four or more embryos (17.1 percent) but were equally low in all women over 40 years even with more embryos (6.1 percent). In the age bands 25 to 29, 30 to 34, 35 to 39, and 40 to 44 years, the rates per embryo of implantation were 18.2 percent, 16.1 percent, 15.3 percent, and 6.1 percent, respectively, and of a live baby were 15.7 percent, 12.1 percent, 12.0 percent, and 3.5 percent. CONCLUSIONS: Embryo implanting ability and survival decline gradually after 30 years of age, but by more than two thirds after 40 years and in younger women with reduced ovarian capacity.

Adult↗
PubMed1996

Stress and stress-related hormones during in-vitro fertilization treatment.

Whether stress and infertility are linked as cause or consequence is unclear, and there is no consensus on the most appropriate methods for measuring stress in infertile women. To address this question, we measured changes in biochemical and questionnaire-based assessments of stress in infertile women. Median baseline, follicular phase and pre-operative serum prolactin (229, 311 and 457 mIU/l) cortisol (278, 369 and 496 nmol/l) and state anxiety score (38, 40 and 49) respectively all increased during stimulated in-vitro fertilization (IVF) treatment. There was no such increase in a control group having similar laparoscopic surgery unrelated to infertility, or in women having unstimulated IVF without laparoscopy, suggesting that anxiety levels are greatest in stimulated IVF, increase as a result of the treatment, and are adequately reflected by state anxiety scores. Baseline serum prolactin in unstimulated IVF (384 mIU/l) was significantly higher than control (177 mIU/l), although this was not reflected in serum cortisol or state anxiety score. Trait anxiety was constant within and between groups, suggesting that stress is not contributing greatly to the infertility. Women who achieved a pregnancy had similar state anxiety scores to those who failed, suggesting that the degree of anxiety observed during IVF treatment is unlikely to influence the chance of pregnancy. There was a trend towards lower trait anxiety in women who became pregnant, but the numbers were small.

Anxiety↗
PubMed1996

Effect of progestogen therapy on follicular development, related hormone concentrations and fertilization in vitro in unstimulated cycles and unexplained and endometriosis-associated infertility.

Evidence of pituitary-ovarian dysfunction in unexplained and endometriosis-associated infertility has been reported previously. Hormone-suppressive therapy is often used in an attempt to improve fertility, although benefits have not been proven. Our study examines the effect of progestogen (medroxyprogesterone acetate) treatment on women with endometriosis-associated and unexplained infertility, compared with women with tubal damage as functional controls. Pre-ovulatory follicular size and serum and follicular fluid hormone concentrations were measured, and oocyte collection and in-vitro fertilization were attempted, in natural cycles totally unperturbed by exogenous gonadotrophins, for two cycles before and two cycles following treatment with medroxyprogesterone acetate for 2 months. In the endometriosis and unexplained infertility groups, compared with the tubal group, the treatment led to significant reductions in the integrated luteinizing hormone (LH) values (483 versus 664, 559 versus 762 and 864 versus 820 notional IU/l respectively). There were no changes in serum oestradiol or follicular fluid oestradiol, progesterone, follicle stimulating hormone or LH concentrations after treatment. The results suggest that progestogen therapy has no beneficial effect on the pituitary-ovarian dysfunction which contributes to endometriosis-associated and unexplained infertility.

Case-Control Studies↗
PubMed1996

Randomized controlled trial of cervical cap with intracervical reservoir versus standard intracervical injection to inseminate cryopreserved donor semen.

A prospective controlled study of donor insemination without sperm preparation or ovarian stimulation was performed to compare the use of a cervical cap incorporating an intracervical reservoir with a standard intracervical injection technique to inseminate 0.5 ml cryopreserved semen. Treatments were alternated in successive cycles in each patient after initial randomized selection. A total of 198 patients had 635 treatment cycles (median 3, range 1-7), 309 with reservoir and 326 by standard injection. A total of 56 women became pregnant, 24 (7.8% per cycle) with the reservoir and 32 (9.8% per cycle) by injection. There were no significant differences between the pregnancy rates per cycle overall or cycle-specific cumulative rates calculated using the life-table method. There were no significant differences in age, parity, baseline gonadotrophin measurements, mid-luteal serum progesterone concentrations, frequency of adverse fertility factors in the woman or her partner's cause of infertility between women who conceived and those who failed to conceive. We conclude that use of a cervical reservoir and cap for donor insemination does not offer any advantage over standard intracervical insemination.

Adult↗
PubMed1996

Antibiotic treatment based on seminal cultures from asymptomatic male partners in in-vitro fertilization is unnecessary and may be detrimental.

We questioned the policy of routine microbiological culture of semen prior to in-vitro fertilization (IVF) with a view to prescribing antibiotics to reduce the risk of introducing seminal infection into the embryo culture system. An initial retrospective study examined serum microbiology reports of 449 couples undergoing IVF or gamete intra-Fallopian transfer (GIFT). In semen samples taking >/=1 days to reach the microbiology laboratory compared with same-day delivery there was increased frequency of significant culture of enterococci (27 versus 15%, P < 0.01). In samples taking >/=2 days there was increased frequency of significant culture of Gram-negative bacilli (31 versus 12%, P < 0.01) and of overall culture of other potentially pathogenic organisms (26 versus 14%, P < 0.01). We questioned diagnostic accuracy and relevance. Therefore, in a prospective study, semen and high vaginal swabs obtained on the day of oocyte collection were cultured from 100 couples having IVF or GIFT, of whom 52 male partners had been treated with antibiotics following positive pre-IVF semen culture. The presence of bacteria in semen samples used only for IVF (n = 90) did not reduce fertilization rates nor lead to infection of the embryo culture system. However, there was an increased incidence of significant culture of vaginal Gram-negative bacilli in patients with treated partners compared with untreated partners [15/52 (29%) versus 5/48 (10%), P < 0.05]. Thus antibiotic therapy in the male partner may increase the likelihood of inoculation of antibiotic-resistant pathogenic bacteria from the vagina into the embryo culture system during vaginal oocyte collection. In asymptomatic patients, microbiological screening of semen samples prior to IVF treatment and subsequent treatment with antibiotic therapy in those with positive cultures appears to be unnecessary and may be detrimental to IVF outcome.

Adult↗
PubMed1996

The indirect immunobead test for seminal antisperm antibodies and fertilization rates at in-vitro fertilization.

A series of 183 patients with positive indirect immunobead tests on semen was studied to determine the correlation in semen between specific antibody types, binding sites, antibody concentration, and fertilizing ability. IgM was present in only 44 ejaculates and was present in sufficient quantity to cause significant binding to immunobeads (i.e. >20% of motile donor spermatozoa) in only three of them. There was no correlation between the percentages of motile donor spermatozoa that bound IgA and IgG immunobeads but the two classes of beads generally bound to the same region of the spermatozoa. A total of 63 couples went on to attempt in-vitro fertilization (IVF) treatment, all with mature eggs recovered. Of these mature eggs, 44% were fertilized and cleaved normally in comparison to 68% in a group of patients with tubal disease. Fertilization rates in individuals followed a bimodal distribution with a substantial number of couples experiencing zero or very poor rates (0-20%), the mode for the remainder lying between 60 and 80%. The fertilization rate tended to decrease as the amount of antibody increased. The percentage of donor spermatozoa that bound to immunobeads, taken as the greater of IgA and IgG, was selected by logistic regression as a significant predictor of poor fertilization (rate <=25%). The predictive power of the equation was improved by including the motile normal sperm concentration but the equation could only account for a small proportion of the total variation in fertilization rate. The presence of antibodies to the sperm head was highly correlated with the antibody concentration but was not selected as a predictor of fertilization. We conclude that the nature of the antigen against which the seminal antisperm antibody is directed may be as important as the antibody concentration in affecting sperm function. There seems to be little practical value in measuring IgM in seminal plasma.

Adult↗
PubMed1996

Impaired implantation after in vitro fertilisation treatment associated with hydrosalpinx.

OBJECTIVE: To study whether the presence of hydrosalpinx affected success after in vitro fertilisation (IVF) in women with inflammatory tubal damage. DESIGN: Retrospective, nonrandomised study. SETTING: University private IVF clinic with complete fertility services. PARTICIPANTS: Two study groups (79 women with hydrosalpinges and 198 women with inflammatory tubal damage but no hydrosalpinx) and a third group (22 sterilised, previously fertile women) for comparison. MAIN OUTCOME MEASURES: Clinical pregnancy and livebirth rates per embryo transfer cycle; implantation and live baby rates per individual embryo transferred. RESULTS: The hydrosalpinx group had a significantly lower implantation rate per embryo (8.2%) and chance of a live baby per embryo transferred (5.6%), compared with the nonhydrosalpinx group (14.9% and 11.2%, respectively). The hydrosalpinx group also had a lower clinical pregnancy rate (23%) and live birth rate per transfer cycle (17%) compared with the nonhydrosalpinx group (30% and 26%), but these differences were not significant. CONCLUSIONS: The presence of a hydrosalpinx halves the chance of an embryo implanting, probably due to physical or toxic chemical effects of fluid draining from the hydrosalpinx into the uterine cavity. Women with hydrosalpinges may benefit from distal salpingostomy or salpingectomy as a drainage procedure before in vitro fertilisation treatment, even though such surgery may not increase the chances of natural conception.

Adult↗
PubMed1996

Reduced preovulatory granulosa cell steroidogenesis in women with endometriosis.

To examine the cause of altered follicular fluid steroid levels and lower in vitro fertilization rate observed in infertile women with minor endometriosis, we have compared the production of estradiol (aromatase activity) and progesterone of freshly isolated granulosa cells (3h. incubation) from such women and a control group with tubal or unexplained infertility, having IVF during unstimulated or gonadotropin-stimulated cycles. As previously observed, mature oocytes from women with endometriosis had a reduced fertilization and cleavage rate in vitro in unstimulated cycles (19/37[51%] vs. 69/94[73%], p < 0.05) and stimulated cycles (20/37[57%] vs. 32/39[82%], p < 0.01). Median [95%CI] basal aromatase activity was lower in endometriosis compared with control in unstimulated cycles (2.84[2.03-3.49] pmol E2/10(3) cells/3h, n = 31 vs. 3.63[2.72-3.49], n = 55, p = 0.057) and stimulated cycles (0.31[0.16-0.50], n = 14 vs. 0.99[0.70-1.52], n = 20, p < 0.001). Progesterone production followed a similar pattern in unstimulated (0.56[0.50-0.89] pmol/10(3) cells/3h, n = 29 vs. 1.23[0.69-1.54], n = 52,) and stimulated (0.37[0.20-0.73], n = 16 vs. 0.95[0.72-1.17], n = 21) cycles (p < 0.05). Addition of FSH, LH or hCG (30ng/mL) to the incubation medium enhanced progesterone production 2 to 3-fold, but had no effect on aromatase activity. Our results indicate a defect in granulosa cell steroidogenesis associated with endometriosis, which could affect oocyte function and explain the reduction in fertilizing capacity and subsequent competence of the corpus luteum, and the associated subfertility.

Aromatase↗
PubMed1996

Managed care of infertility.

Mandated managed care of infertility, as for other branches of medicine, demands cost-effectiveness, appropriate use of proven clinical methods, and audit of the services provided. Proper standards, and protocols of clinical diagnosis and selection of treatment need to be agreed, although allowing for valid alternatives. A diagnostic process and classification staged for primary, secondary, and tertiary care as appropriate, which has been derived by consensus, is offered in this paper. It is assumed that all couples would be allowed access to diagnostic services. A national estimate has attributed one-quarter of the costs of full infertility services to diagnostic procedures and three-quarters to treatments. It is assumed that any constraints owing to funding would apply only to access to treatment. One model proposed would limit treatment to those couples and methods which could achieve a 50% birthrate target within a reasonable time limit or number of cycles. Although there is as yet no existing model of managed care on which to base exact costing, it should be possible by initial over-restrictiveness to leave room for annual adjustments of treatment provision and to allow for new developments. Other more equitable ways of sharing resources can be argued, and ethical standards should be agreed in any system of managed care for a population.

Cost-Benefit Analysis↗
PubMed1995

Gonadotrophin surge-attenuating factor bioactivity is present in follicular fluid from naturally cycling women.

Rat pituitary monolayer bioassays were used to compare gonadotrophin surge-attenuating factor (GnSAF) bioactivity in follicular fluid from 12 follicles in 10 spontaneously cycling women with that in pooled follicular fluid from women undergoing ovulation induction. Expressed as ED50S (microliter follicular fluid/well producing 50% of maximal effect), GnSAF bioactivity was detectable in all spontaneous follicular fluid samples (1.4-33.3 microliters/well) and in follicular fluid from women undergoing ovulation induction (6.8 microliters/well). This GnSAF bioactivity was unaffected by pre-incubation with an inhibin antibody. When the data were grouped according to whether the recovered oocytes fertilized in vitro or not, the fertilized group contained significantly greater GnSAF bioactivity than the unfertilized group (5.3 +/- 1.1 and 14.1 +/- 2.6 microliters/well respectively, P < 0.05). While both inhibin bioactivity (9.7 +/- 1.4 and 28.9 +/- 12.1 microliters/well) and immunoreactivity (36.8 +/- 2.2 and 21.0 +/- 3.0 and ng/ml) were also greater (P < 0.01) in the fertilized compared with the unfertilized groups respectively, there were no other significant differences between the two groups. We conclude that GnSAF is found in follicular fluid from spontaneously cycling women, supporting in-vivo evidence for the involvement of GnSAF in feedback control of the ovary-pituitary axis.

Adult↗
PubMed1995

Time-dependent effects of transforming growth factor alpha on aromatase activity in human granulosa cells.

Transforming growth factor alpha (TGF alpha) is implicated as a paracrine growth factor in the regulation of human granulosa cell function. To investigate this further, we have examined the actions of TGF alpha on the basal and follicle-stimulating hormone (FSH)-stimulated aromatase activity of human granulosa cells to determine how this growth factor influences oestrogen biosynthesis in the follicle. Granulosa cells from women having in-vitro fertilization during untreated or gonadotrophin-stimulated cycles were cultured for 1-6 days in the presence or absence of FSH or TGF alpha at a range of doses. Aromatase activity, expressed as oestradiol production, was determined after culture during a 3 h test period. After 2 days, TGF alpha (1-300 ng/ml) decreased basal and FSH-stimulated aromatase activity in a dose-dependent manner (ED50 = 3 ng/ml). In contrast, after 4 days, TGF alpha enhanced both basal and FSH-stimulated aromatase activity. Repeated experiments revealed a consistent pattern of inhibition on day 2, which was more marked in the presence of FSH (reduction by 30.6 +/- 9.1%, mean +/- SEM; n = 14; P < 0.01), and stimulation on day 4 in both the absence (increased by 61.4 +/- 20.6%, mean +/- SEM; n = 6; P < 0.05) and presence of FSH (increased by 36.0 +/- 15.2%, mean +/- SEM; n = 8; P < 0.05). The results provide further evidence that TGF alpha is a paracrine factor in the control of oestrogen biosynthesis, but the actions can be either inhibitory or stimulatory depending on the duration of exposure.

Aromatase↗
PubMed1995

Pituitary-ovarian dysfunction as a cause for endometriosis-associated and unexplained infertility.

This study examines circulating and follicular hormone concentrations and fertilization of oocytes in cycles totally unperturbed by exogenous gonadotrophins in 10 women (25 cycles) with untreated minimal-mild endometriosis and nine women (23 cycles) with prolonged unexplained infertility compared with 16 women (50 cycles) with tubal damage as functional controls. Endometriosis was associated with a significantly longer follicular phase (median 15, 12, 13 days respectively) and reduced oestrogen secretion (median index area under the curve 3063, 3842, 3805 units respectively) compared with controls. Both endometriosis and unexplained infertility had significantly reduced serum luteinizing hormone (LH) surges [median peak serum (LH) 43, 39, 55 IU/l respectively and median area under the curve 661, 687, 823 units respectively] and reduced LH concentrations in follicular fluid (median 19.6, 10.6, 9.2 IU/l respectively). These findings suggest that infertility associated with minor endometriosis and of apparently unexplained aetiology share a common pathophysiology in impaired LH surge secretion. Whether that represents a primary pituitary disorder or is secondary to a defective ovarian signal is discussed.

Adult↗
PubMed1995

Testing the mutagenic potential of polyvinylpyrrolidone and methyl cellulose by sister chromatid exchange analysis prior to use in intracytoplasmic sperm injection procedures.

The treatment of infertility due to severe oligoasthenoteratozoospermia has been revolutionized by the introduction of the technique of intracytoplasmic sperm injection. However, techniques which involve injection into the oocyte of polyvinylpyrrolidone solution as a vehicle for the selected spermatozoon have caused concern since the possible harmful effects of polyvinylpyrrolidone have not been fully investigated. This study was performed to investigate the potential mutagenic effect of polyvinylpyrrolidone on cultured human somatic cells, at the concentration used for intracytoplasmic sperm injection, in addition to a possible alternative vehicle, methyl cellulose, using the technique of sister chromatid exchange analysis. The results showed no increase in the basal frequency of sister chromatid exchanges with polyvinylpyrrolidone (median 5.0, 95% interval 5.00-6.00) or with methyl cellulose (median 6.0, 95% interval 4.22-6.00) in comparison with the negative control (saline: median 6.0, 95% interval 5.00-7.00), and in contrast to the positive control (mitomycin C: median 25.0, 95% interval 22.23-28.77). This finding suggests that polyvinylpyrrolidone and methyl cellulose do not cause DNA lesions resulting in sister chromatid exchanges, and provides reassuring evidence concerning their use in sperm injection procedures.

Cytoplasm↗
PubMed1995

In-vitro fertilization in completely natural cycles.

Our objective was to assess the efficacy of in-vitro fertilization (IVF) in natural ovarian cycles in couples with tubal and unexplained infertility. A prospective study design was used. A total of 39 fully investigated couples, who were patients at the Reproductive Medicine Unit, St Michael's Hospital, Bristol, UK, took part; they were diagnosed with either tubal disease (n = 26) or unexplained infertility (n = 13). Procedures involved daily capillary blood sampling, daily vaginal ultrasonography and vaginal oocyte recovery under sedation at mid-cycle. The main outcome measures were fertilization, implantation and pregnancy rates. Although more of the women with tubal disease were parous, there were no other significant differences between the two groups. The 39 couples with infertility of tubal or unexplained aetiology had 79 cycles of IVF in otherwise completely natural cycles. The overall fertilization rate was 80% and the implantation rate was 14.0%. A trend was observed for higher success rates in women with tubal disease. We conclude that natural cycle IVF and embryo transfer offers an acceptable chance of pregnancy and an opportunity for the in-depth investigation of follicular and ovarian function in couples with defined causes of infertility. The possibly lower success rate in women with unexplained infertility warrants further study of follicular function and endocrinology.

Adult↗