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Biomedical subjects

M G Hull

Publications and source records attributed to M G Hull.

At least 55 records · Page 3Linked to original sources
PubMed1995

Tubal surgery versus assisted reproduction: assessing their role in infertility therapy.

The majority of women with tubal/pelvic infective damage have a poor prognosis for natural conception, and in-vitro fertilization and embryo transfer would be a better primary choice. Other determining factors are sperm disorder or the woman's age, and personal issues may be of overriding importance. The most important requirement in the first place, however, is well defined, comparable statistical information on time-specific cumulative pregnancy rates related to specific diagnostic features. The main aims of this review are to analyze the most useful comparable data available and present them in graphical form for easy reference and clear understanding (by the patients too), and to try to derive a practically simple and prognostically valuable diagnostic classification.

Adult↗
PubMed1995

Experience using preparations of follicle-stimulating hormone alone to stimulate the ovaries for assisted conception after pituitary desensitisation and simplified management of treatment.

The results are reported of 2,204 cycles of treatment started for in vitro fertilisation and embryo transfer or gamete intrafallopian transfer, during 5 years, 1990-1994, using only follicle-stimulating hormone (FSH) preparations to stimulate the ovaries following pituitary desensitisation, combined with greatly simplified scheduling and monitoring of treatment. The physiological principles underlying these choices are discussed. In all women under 40 years of age and men with normal sperm, the use of unpurified urinary FSH in 1990-1993 resulted in oocyte collection in 94% of cycles started, pregnancy in 29% and live births in 23%. Using highly purified urinary FSH (uFSH-HP; Metrodin HP) during 1994, the rate for oocyte collection was 97% and pregnancy 25% (birth rates not yet available). The difference compared with previous years was not significant. A study of 93 first cycles using uFSH-HP showed that the dosage required was usually (expressed as medians) 24 ampoules over 12 days (2 ampoules/day) resulting in 9 oocytes (range 2-36) of which 93% were mature and 64% resulted in cleaving embryos. The results are comparable with the best using human menopausal gonadotropin or unpurified FSH and classical detailed monitoring.

Adult↗
PubMed1994

Effectiveness of infertility treatments: choice and comparative analysis.

Choice of infertility treatments usually depends on a balance of the chances of conceiving with or without treatment, and with more or less complex and costly treatments, and on other factors such as duration of infertility and the woman's age. Pregnancies often occur independent of treatment and prospective controlled trials are needed. Comparability between reported results requires pregnancy and birth rates to be calculated in a time-specific or cycle-specific way. Cumulative rates are preferable to account for the usual tendency of fecundity to fall progressively. This review focuses on such published data in order to assess the relative effectiveness of treatments, both conventional and assisted conception methods. The main conclusions are: (1) The only treatments that can achieve a normal chance of pregnancy are the ovulation induction methods in cases of oligomenorrhea/amenorrhea, and the assisted conception methods for other female causes and unexplained infertility. (2) Tubal/pelvic infective damage and endometriosis require new severity classifications which are sensitive to functional potential before and after surgery, and in vitro fertilization (IVF) would often be indicated as the primary choice. (3) Duration of unexplained infertility determines the need and therefore benefit of any of the treatments used, of which the assisted conception methods are by far the most effective. (4) Interpretation of reported results of treatments for 'male factor' infertility is critically affected by the diagnostic accuracy of defining sperm dysfunction. (5) In cases of well-defined sperm dysfunction there is little or no therapeutic benefit to the chance of natural conception, nor by intrauterine insemination; there is moderate success by IVF, but no proven benefit over standard IVF by any micromanipulative method except probably intracytoplasmic sperm injection.

Female↗
PubMed1994

Use of follicle-stimulating hormone alone (urofollitropin) to stimulate the ovaries for assisted conception after pituitary desensitization.

OBJECTIVE: Analyse outcome of FSH therapy alone after pituitary desensitization for assisted conception to compare with published results of conventional hMG. DESIGN: Descriptive study of complete series of patients undergoing IVF-ET or GIFT treatment using the chosen drug protocol without exception. SETTING: University private IVF-ET clinic within a comprehensive fertility service. PATIENTS: All couples (n = 773), including 10% > or = 40 years old, treated by IVF-ET or GIFT (1,097 cycles started and 1,012 attempted egg recoveries) for mainly tubal pelvic infective damage (36% of cycles), endometriosis (16%), sperm disorders (14%) and prolonged unexplained infertility (34%) during 3 calendar years, 1990 to 1992. INTERVENTIONS: Ovarian stimulation using FSH alone (urofollitropin, Metrodin; Serono Laboratories Limited, Welwyn Garden City, United Kingdom) after pituitary desensitization using buserelin acetate nasal spray (Suprefact; Hoechst, Hounslow, United Kingdom) from the previous midluteal phase, monitored by ultrasonography and serum E2 measurements, followed by standard IVF-ET or GIFT treatment methods limited to the transfer of no more than three embryos or eggs. OUTCOME MEASURES: Rates per cycle started of cancellation of egg recovery, failure of egg recovery, clinical pregnancy (ultrasound detection of sac), livebirths, and cumulative pregnancy rates (PR) and birth rates. RESULTS: In women < 40 years old and men with favorable sperm (77% of couples and 84% of cycles) the cycle cancellation rate of egg recovery was 7%; attempted egg recovery was successful in every case. For IVF-ET the clinical PR per started cycle and the livebirth rate were 27% and 23%, respectively, and for GIFT 39% and 33%, respectively. The four-cycle cumulative PR by either treatment was 77% and livebirth rate 68%. In women > 40 years old, the cycle PR and birth rate were 14% and 8%, respectively. In cases of sperm disorder the rates in women < 40 years old were 17% and 14%, respectively, and > 40 years old were 18% and 0, respectively. CONCLUSIONS: By comparison with the best worldwide results of assisted conception employing pituitary desensitization, the findings demonstrate that FSH alone to stimulate the ovaries is fully effective and highly successful, and supplementation with LH is not needed.

Adult↗
PubMed1994

Apparent lack of seasonal variation in implantation rates after in-vitro fertilization.

It has been suggested that seasonal variation in endometrial receptivity may occur in women, which could affect the likely success of in-vitro fertilization (IVF) treatment. We therefore studied implantation rates (fetal sacs as a proportion of embryos transferred) as an indirect index of receptivity in a narrowly defined population of women under 40 years old with normal ovulatory cycles and normal uterus and men with normal sperm function. A total of 577 cycles of IVF treatment were undertaken using a standard protocol of pituitary desensitization and ovarian stimulation during the 3 years 1990-1992. Results were compared between calendar months and 3-month seasons. The overall implantation rate was 14.9% of embryos, and the clinical pregnancy rate was 30.3% of cycles reaching egg collection. There were no significant differences in the monthly rates of eggs collected, fertilization and cleavage, or embryos transferred. Implantation rates varied to a greater extent but analysis of variance showed no seasonal variation. These findings do not support a seasonal variation in ovarian responsiveness or endometrial receptivity when stimulated for IVF treatment, but larger studies are needed for firm conclusions to be drawn.

Adult↗
PubMed1994

The prognosis for assisted conception treatment after unexpected failure of fertilization in vitro: a comparative study.

The relative prognosis for further assisted conception treatment (without micro-injection) after initial unexpected failure of fertilization in apparently favourable couples undergoing in-vitro fertilization (IVF) treatment was assessed. After their first cycle of treatment, 481 consecutive couples were grouped according to their fertilization (including cleavage) rate per oocyte into five bands. Proportions of couples proceeding to further cycles of treatment by IVF or gamete intra-Fallopian transfer (GIFT) and resulting fertilization and pregnancy rates were compared. Pregnancy rates in the first cycle of treatment were significantly related to fertilization rate. The fertilization rate was zero in 13 couples (3%) and only 1-24% in 18 (4%). There were no significant differences between these groups in the proportions proceeding to further treatment (31, 50%) compared with others (overall 37%, including some treated by GIFT), or in their median fertilization rates (75, 60% compared with 67%--IVF cycles only), pregnancy rates (20, 38% of cycles compared with 37%--IVF or GIFT) or birth rates (20, 38% of cycles compared with 31%--IVF or GIFT). Amongst couples whose initial fertilization rate was > or = 50% there was no fertilization in 4% of subsequent IVF cycles. We conclude that in couples with well defined favourable conditions, including tests of sperm function for assisted conception treatment, who have unexpected failure of fertilization, the prognosis for further treatment remains favourable without resort to more complex investigations or micro-injection methods. Such failure occurs infrequently and generally as a random event, and should have no appreciable effect on life-table calculation of cumulative pregnancy and birth rates in this group of patients.

Fertilization in Vitro↗
PubMed1994

The effect of halving the standard dose of cryopreserved semen for donor insemination: a controlled study of conception rates.

Employing a common standard technique of intra-cervical insemination from straws of cryopreserved donor semen, a volume of 0.25 ml of 0.5 ml was inseminated in alternate cycles to determine if the lower volume could be used without a decrease in the conception rate. A total of 177 women were recruited and received a median of four cycles of treatment. Of these, 90 women became pregnant, 47 with 0.5 ml and 43 with 0.25 ml inseminations. The conception rates were identical for both volumes in the first nine cycles of treatment and the cumulative rates were 57.7 and 59.3%, respectively. Subsequently more pregnancies were achieved with 0.5 ml than 0.25 ml semen (nine pregnancies in 73 further cycles versus three pregnancies in 68 cycles, respectively), although the difference was not statistically significant. There were no significant differences in the women's ages, luteinizing hormone, follicle stimulating hormone, progesterone, mucus quality, mucus pH, parity or partner's diagnosis between those women who became pregnant and those who failed to conceive with either insemination dose. We conclude that the volume of semen inseminated into the cervical canal without a cervical cap can be decreased to 0.25 ml without an adverse effect on the conception rate at least in the first 9 months of treatment. This will allow more effective use to be made of valuable screened and quarantined cryopreserved semen.

Adult↗
PubMed1994

Outcome of inadvertent administration of a gonadotrophin-releasing hormone agonist (buserelin) in early pregnancy.

All women undergoing pituitary down-regulation before planned in-vitro fertilization (IVF) treatment in two IVF units were studied to assess the risks of and to pregnancies occurring inadvertently when gonadotropin-releasing hormone agonists (GnRHa) were used to achieve pituitary desensitization during the luteal phase prior to planned IVF treatment. In 2670 cycles, 25 women conceived (0.9% of cycles). Of these, three resulted in pre-clinical abortions (12%) but there were no clinical abortions, and 22 have ended with live births at term of apparently normal infants. Collation of these and other published data suggest that pregnancy outcome is not adversely affected by GnRHa administration in the luteal phase of the conception cycle.

Abortion, Spontaneous↗
PubMed1994

Adenosine triphosphate and motility characteristics of fresh and cryopreserved human spermatozoa.

The concentration of ATP and the motility of human spermatozoa was measured in fresh and cryopreserved cells from the same 15 ejaculates. No coherent picture of the relationship between motility and ATP concentration emerged in whole semen or in spermatozoa washed by repeated centrifugation and resuspension in Biggers Whitten and Whittingham medium. This may have been due to the presence of dead spermatozoa and contaminating cells. After preparation on a Percoll gradient, the ATP concentration in fresh and cryopreserved spermatozoa was the same (6 +/- 0.7 nmol/10(8) spermatozoa) but 85 +/- 2.5% of the fresh spermatozoa were progressively motile with an average path velocity of 55 +/- 3.5 microns/s compared to corresponding values of 33 +/- 5.3% and 44 +/- 3.4 microns/s in frozen/thawed spermatozoa. This suggests that the poor motility of cryopreserved spermatozoa does not result from deficient ATP production. No relationship was found between ATP concentration and the ability of motile spermatozoa in the ejaculate to survive freezing.

Adenosine Triphosphate↗
PubMed1994

Pentoxifylline acts synergistically with A23187 to increase the penetration of zona-free hamster oocytes by cryopreserved human spermatozoa.

The number of cryopreserved human spermatozoa which penetrated zona-free hamster oocytes after stimulation with 2 mumol A23187 per litre was increased by the further addition of 0.6 or 3.6 mmol pentoxifylline per litre. With spermatozoa prepared by washing by repeated centrifugation, the median numbers of sperm heads/egg were 1.9, 7.9 and 10.8 in the presence of 0, 0.6 or 3.6 mmol pentoxifylline per litre, respectively. A similar effect was observed with spermatozoa prepared on a Percoll gradient. As A23187 inhibited sperm motility, and this was exacerbated by pentoxifylline, the increased penetration rate of hamster oocytes cannot be explained by improved sperm motility. The number of spermatozoa stimulated to acrosome react by 2 mumol A23187 per litre was increased 3-fold by 3.6 mmol pentoxifylline per litre and 4-fold by 5 mmol caffeine per litre. These data suggest that cAMP may act synergistically with Ca2+ to stimulate the acrosome reaction. Pentoxifylline may improve the fertility of poor-quality human spermatozoa by enhancing their ability to respond to the Ca2+ signal produced by binding to the zona pellucida.

Acrosome↗
PubMed1994

Relative influence of serum follicle stimulating hormone, age and other factors on ovarian response to gonadotrophin stimulation.

OBJECTIVE: To determine the relative value of the woman's age, basal follicle stimulating hormone (FSH), basal luteinising hormone (LH) and menstrual cycle pattern (all defined prior to treatment) in predicting the ovarian response to gonadotrophin stimulation for in vitro fertilisation. DESIGN: Open, descriptive cohort study. PATIENTS: One hundred and seventy-one consecutive ovulatory women undergoing their first cycle of in vitro fertilisation with ovarian stimulation after pituitary desensitisation. INTERVENTIONS: Measurement of basal (early follicular phase) and down-regulated concentrations of serum FSH and LH, and calculation of age at treatment and of median length of menstrual cycles and range of variation prior to treatment. MAIN OUTCOME MEASURES: Duration and amount of gonadotrophin stimulation to achieve follicular maturity, number of mature follicles, peak serum oestradiol concentration and number of mature oocytes, were compared between banded values of variables studied. RESULTS: Increasing basal FSH concentrations were significantly associated with reducing oestradiol levels, numbers of mature follicles and oocyte yield even when the FSH levels were still within the normal range though above average (6 to 8.9 i.u./l). There were similar but weaker associations with FSH levels after down-regulation. There were also significant differences between women over and under 40 years old in their oestradiol levels, numbers of follicles and of oocytes. Analysis of variance showed significant independent association of basal FSH with both oestradiol and numbers of oocytes, but not of age, menstrual pattern, or serum LH concentrations. CONCLUSION: Serum FSH is more sensitive than the woman's age in determining her ovarian responsiveness to stimulation. LH concentrations and menstrual cycle patterns are unhelpful.

Adult↗
PubMed1994

Higher gonadotrophin surge-attenuating factor bioactivity is found in small follicles from superovulated women.

Ovine and rat pituitary bioassays for gonadotrophin surge-attenuating factor (GnSAF) were utilized to determine whether the level of GnSAF bioactivity in pooled human follicular fluid (hFF) from superovulated women varied according to follicle diameter (< or = 11 mm, 12-15 mm and 16-21 mm follicles examined using the ovine bioassay, or < or = 10 mm, 11-13 mm, 14-17 mm, 18-20 mm, 21-24 mm and > or = 25 mm follicles examined using the rat bioassay). When tested using dispersed ovine pituitary cells, GnSAF bioactivity, expressed in terms of the reduction in gonadotrophin-releasing hormone (GnRH)-induced LH secretion, was inversely related to follicle diameter (P < 0.01). In response to 5 microliters hFF/well from follicles of < or = 11, 12-15 and 16-21 mm diameter, GnRH-induced LH secretion was reduced to 40.5 +/- 6.9%, 65.2 +/- 6.6% and 83.7 +/- 7.9% of control respectively. A similar inverse relationship was observed when a second batch of hFF samples from different sized follicles was tested using rat pituitary cell monolayers. Expressing GnSAF bioactivity in terms of the dose required to suppress GnRH-induced LH secretion by rat pituitary cells to 50% of the maximal suppression observed (ED50), the three smallest follicle size pools contained the most GnSAF (ED50 values of 0.13, 2.79 and 5.36 microliters hFF/well from follicles of < or = 10, 11-13 and 14-17 mm respectively). The ED50 values for follicles of 18-20, 21-24 and > or = 25 mm were 8.81, 27.1 and 60.0 microliters hFF/well respectively. Thus hFF from follicles < or = 11 mm was over 450 times more potent than hFF from follicles > or = 25 mm in suppressing GnRH-induced LH release. The ED50 values for inhibin bioactivity (measured as the suppression of basal FSH secretion from rat pituitary monolayers) were much less variable than those for GnSAF bioactivity (between 0.85 and 0.13 microliters hFF/well). Inhibin immunoreactivity, measured by a two-site immunoradiometric assay, followed the same pattern as inhibin bioactivity with lowest concentrations in the smallest follicles (41.96 ng/ml) and highest concentrations in the three largest follicle size groups (56.48-64.48 ng/ml). The specific effects of inhibin on GnRH-induced LH and basal FSH release in these pituitary bioassays were determined by incubating culture dishes with pure recombinant human inhibin at doses of 0.025-25 ng/well. In both the sheep and rat pituitary monolayers, basal FSH was suppressed (ED50 = 0.02 and 0.16 ng/well respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Is endometriosis a disease?

Recent comparative studies and developments in our understanding of the pathogenesis and pathophysiology of endometriosis have led to increasing doubts about whether it should always be considered a disease. Widespread use of laparoscopy for gynaecological investigation and treatment, recognition of non-pigmented lesions which are more active than classical implants, and the documentation of microscopic lesions in visually normal peritoneum, have all resulted in an increase in the frequency with which endometriosis is diagnosed. Recent studies suggest a prevalence of up to 80% in women complaining of infertility or pelvic pain, but also in up to 22% of fertile asymptomatic women undergoing sterilization. Perhaps it is a normal physiological variant, being present in such a high proportion of the population. Circumstantial evidence suggests this may be so, and the results with placebo treatment in controlled trials suggest that endometriosis is self-limiting and will regress or disappear spontaneously in 58% of women. The frequency and severity of symptoms which are often presumed to result from endometriosis do not correlate with the extent or site of lesions. Most women are pain-free. There is no dysmenorrhoea in up to 77%, no dyspareunia in up to 70%, and no pelvic pain at all in up to 61% of women with endometriosis. The pathophysiology of pain related to endometriosis is not understood. There is no medical or conservative surgical treatment that is wholly effective for symptom relief, and there is considerable placebo benefit. All treatments have risks or side-effects, and recurrent symptoms will develop in up to 45% of women within 5 years. For these reasons treatment should only be used where endometriosis fulfils the criteria of a disease, showing signs of progression with tissue damage or physiological disturbance. Asymptomatic endometriosis without tissue damage should not be considered a disease and should not be treated. Treatment of pain associated with minor endometriosis, or prophylactic treatment to prevent progression, must be regarded as empirical and not the specific requirement to control what is a questionable disease.

Adolescent↗
PubMed1993

Effects of cryopreservation on the human sperm acrosome and its response to A23187.

The proportion of human spermatozoa from 28 ejaculates to lose their acrosomes during cryopreservation was measured and correlated with the number that became immotile or lost the integrity of their plasma membrane. The ability of washed spermatozoa to acrosome react in response to A23187 before and after cryopreservation was compared. Motility was assessed by time-lapse photography; intact acrosomes were stained with fluorescein conjugated Pisum sativum agglutinin and dead spermatozoa were stained with bisbenzimide (H33258). Twenty-four per cent of spermatozoa lost their acrosomes during freezing and thawing, but the number that did so was not correlated with the number that became immotile or non-viable. Frozen spermatozoa exhibited fewer spontaneous acrosome reactions than did fresh spermatozoa (5 versus 13% after 4 h), but they responded to A23187 in a similar way. Although frozen spermatozoa were significantly more likely to die during the incubation, the data do not suggest that degenerative acrosome loss had a major influence on the results. In the hamster egg test frozen-thawed spermatozoa achieved more penetrations than did fresh spermatozoa when stimulated with 0 or 1 mumol A23187 l-1 but considerably fewer when stimulated with 4 mumol A23187 l-1. The following conclusions were made. First, cryopreservation damage to the acrosome, the plasma membrane and the flagellum can occur independently. Second, acrosome function is maintained after cryopreservation as long as the organelle remains mechanically intact. Third, some spermatozoa that lose their acrosomes during cryopreservation remain viable and can fuse with zona-free hamster eggs.

Acrosome↗