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Biomedical subjects

S R Killick

Publications and source records attributed to S R Killick.

At least 37 records · Page 2Linked to original sources

Ultrasound evaluation of the uterine zonal anatomy during in-vitro fertilization and embryo transfer.

This study was designed to establish if ultrasound could detect differences in uterine zonal anatomy between conception and non-conception in-vitro fertilization (IVF)/embryo transfer cycles. A transvaginal ultrasound scan was performed on the day of down regulation (D0), on day 8 of ovulation induction (D8), on the day of human chorionic gonadotrophin (HCG) injection, at the time of oocyte retrieval, and at embryo transfer. Thicknesses of endometrium, junctional zone, myometrium and full thickness of the uterus were recorded for every patient and comparisons made at all the assessment points. Differences between measurements on D0 and all other measurements (temporal changes) and between every subsequent measurement (dynamic changes) were also compared. There were no statistically significant differences in endometrial thickness between pregnant and non-pregnant groups at any time. The diameter of the uterus increased during therapy and was significantly greater in the pregnant subset at the time of HCG injection, oocyte retrieval and embryo transfer (P < 0.02, 0.03 and 0.02 respectively). The myometrium was significantly thicker in the pregnant group on D0, on D8 and at HCG administration (P < 0.03, 0.004 and 0.02). There was a decrease in junctional zone thickness in both groups during the first week of ovulation induction, and on D8 the junctional zone in pregnant patients was significantly thinner (P < 0.04). The junctional zone became significantly thicker at embryo transfer in the pregnant group (P < 0.01). This was confirmed by significant temporal and dynamic changes at the time of oocyte retrieval and embryo transfer (P < 0.01, 0.0001 and P < 0.05, 0.01 respectively). In the patients who did not conceive, changes in the junctional zone were less pronounced. In conclusion, it was not possible to predict the likelihood of pregnancy from endometrial thickness at any time during the IVF cycle, but changes occurred in other uterine layers that were more pronounced in conception cycles. The responsiveness of the junctional zone seems to be associated with implantation, and its measurements at the time of downregulation and embryo transfer can be used to predict treatment outcome.

Adult↗

Ovarian hyperstimulation syndrome and benign intracranial hypertension in pregnancy after in-vitro fertilization and embryo transfer: case report.

Ovarian hyperstimulation syndrome (OHSS) is a dangerous and sometimes life-threatening complication of ovulation induction with exogenous gonadotrophins. While many complications of severe OHSS are recognized we have only identified one review detailing neurological problems. This report concerns a 32-year-old patient with bilateral tubal blockage who achieved her first pregnancy following in-vitro fertilization (IVF) and embryo transfer. Shortly after embryo transfer she developed clinical signs of moderate OHSS with symptoms which were later diagnosed as benign intracranial hypertension (BIH). The BIH was treated effectively using repeated lumbar puncture and diuretics. Spontaneous labour and delivery occurred at 40 weeks' gestation. There was no neurological sequel and no recurrence of the BIH 2 years after the pregnancy. The possible link between OHSS and BIH is discussed as well as the risks of further pregnancy.

Adult↗

Junctional zone contractions and embryo transfer: is it safe to use a tenaculum?

Applying a tenaculum to the cervix is a common practice when the correction of uterine position prior to embryo transfer is required. Our study was designed to assess junctional zone contractility before and after this procedure in 20 patients at the time of mock embryo transfer (mid-luteal phase, at commencement of down-regulation). Real-time transvaginal ultrasound and computer technology was used to evaluate the contraction pattern and frequency. When a tenaculum was applied, the total number of contractions, the number of cervico-fundal, random and opposing contractions all increased significantly (P values 0.0003, 0.005, 0. 001 and 0.007 respectively). Eleven women displayed cervico-fundal contractions, prominent opposing and random contractions were observed in all 20 patients and four patients generated fundo-cervical waves not seen in any case before stimulation with the instrument. In conclusion, manipulation with a tenaculum in the cervical area stimulates junctional zone contractions and is best avoided at the time of embryo transfer.

Cervix Uteri↗

Hysterosalpingo contrast sonography as a screening test for tubal patency in infertile women.

The most informative method for assessing tubal patency in subfertile women is laparoscopy-and-dye. This investigation, however, puts a large burden on services and a screening test is needed that identifies a high likelihood of occlusion. In our infertility programme we introduced hysterosalpingo contrast sonography for this purpose, operated entirely by ultrasonographers. A series of audits indicated that this innovation speeded the process of investigation by several weeks and reduced the number of laparoscopy-and-dye procedures by 75%. The negative predictive value was 89% and the positive predictive value was 44%. The main limitation of the method was the long period required for training, in those without extensive experience of vaginal ultrasonography.

Contrast Media↗

Ovarian activity in women taking an oral contraceptive containing 20 microg ethinyl estradiol and 150 microg desogestrel: effects of low estrogen doses during the hormone-free interval.

OBJECTIVE: We assessed the effect of low ethinyl estradiol doses given during the nominally hormone-free interval of the Mircette (brand of desogestrel/ethinyl estradiol and ethinyl estradiol) contraceptive regimen on ovarian activity. STUDY DESIGN: In a randomized, double-blind study, healthy women received 150 microg desogestrel and 20 microg ethinyl estradiol for 21 days followed by either placebo for 7 days (Mircette/placebo; N = 24) or placebo for 2 days and 10 microg ethinyl estradiol for 5 days (Mircette/ethinyl estradiol; N = 23). RESULTS: During cycles 2 and 3, the Mircette/placebo group had a higher incidence of persistent ovarian follicles (eight subjects versus three subjects) and on average a greater maximum follicle diameter than the Mircette/ethinyl estradiol group. One Mircette/placebo subject probably ovulated in cycle 2, and another had a luteinized unruptured follicle; no such activity was seen in the in the Mircette/ethinyl estradiol group. The study medication was well tolerated, and there were no apparent between-group differences in vaginal bleeding patterns. CONCLUSION: The Mircette regimen, which includes low ethinyl estradiol doses during the hormone-free interval, more effectively suppresses ovarian follicular activity with a low monthly estrogen dose.

Adolescent↗

A prospective clinical trial investigating the efficacy of a method of preparing subpopulations of antibody-free spermatozoa from the ejaculates of antibody-positive patients.

Couples undergoing in vitro fertilization treatment (IVF) were invited to take part in a controlled prospective clinical trial. The aim was to determine the effect on the fertilization rate of a technique devised to obtain an antibody-free preparation of spermatozoa from an antibody-positive ejaculate. Oocytes collected during IVF were allocated into one of two groups, ensuring that quality and maturity were comparable in each. One group, the control, was inseminated with Percoll-processed spermatozoa. The experimental group was inseminated with identical numbers of Percoll-processed spermatozoa which had been treated to obtain an antibody-free preparation. The treatment was found to have no beneficial effect on the fertilization rate at IVF. Laboratory studies were also performed on the ejaculates of antibody-positive volunteers to determine whether this treatment led to any effects, whether beneficial or detrimental, on sperm function. Membrane integrity was found to be unaffected, as was the percentage of spermatozoa undergoing the spontaneous acrosome reaction following overnight incubation. The percentage of spermatozoa undergoing the ionophore-induced acrosome reaction following treatment, however, was higher than that of the controls. The results of sperm-zona pellucida binding studies were equivocal. The findings indicated that the treatment procedure could not be justified for use in IVF, but may be beneficial for intrauterine insemination.

Autoantibodies↗

Embryo transfer--can we learn anything new from the observation of junctional zone contractions?

To assess whether embryo transfer can alter junctional zone contractility, we studied the effect of easy and difficult mock transfers in 14 oocyte donors during in-vitro fertilization (IVF) cycles. An Echovist bolus (30 microl) was used to represent embryos and transfer medium. An 'easy' transfer was judged to be an atraumatic insertion of the catheter without touching the uterine fundus. A 'difficult' embryo transfer was mimicked by deliberately touching the uterine fundus twice with the soft end of the cannula. Transvaginal scan images were recorded, digitized and converted into five times normal speed to allow us to evaluate junctional zone contractility. Easy mock embryo transfers did not change endometrial mechanical activity. Echovist remained in the upper part of the uterine cavity and was not dispersed after 45 min. A difficult procedure generated strong random waves in the fundal area and waves from fundus to cervix which relocated the Echovist in six out of seven cases. We observed movements of the transfer bolus from the upper part of the uterus towards the cervix (four cases) and into Fallopian tubes (two patients). Our study confirms that the mechanical activity of the uterus is capable of relocating intrauterine embryos and that this activity depends on physical stimulation. Junctional zone contractions can be implicated in cases of IVF/embryo transfer failure or ectopic gestation.

Adult↗

A profile of family planning audit in England 1994-1997.

Audit has been entered into enthusiastically by most of the multidisciplinary teams giving family planning services but the nature of the subject makes audit particularly difficult in this field. In many cases it has been used as a tool for determining standards rather than a tool for determining compliance to them. If family planning audit and evaluation is to substantially improve in quality, a great deal of work needs to be done, particularly in the formation of appropriate guidelines and in the increased utilisation of audit/research specialists to advise on methodology. It is hoped that the new clinical effectiveness committee of the faculty will take a lead in this; if so it will undoubtedly gain support from faculty members.

England↗

Human tubal fluid: production, nutrient composition and response to adrenergic agents.

Vascularly perfused Fallopian tubes have been used to study the formation and composition of human tubal fluid and the response to adrenergic agents. An artery serving the tube was cannulated and perfused with Medium 199 supplemented with bovine serum albumin (BSA) and antibiotics. A second cannula was attached to the fimbriated end for native tubal fluid collection. The preparation was viable for up to 2 h. Tubal fluid was only obtained in tubes removed in the proliferative and early secretory phases of the ovarian cycle. Isoproterenol (1 mM) added to the perfusate stimulated fluid production, whereas dibutyryl cyclic AMP (1 mM) reduced fluid formation by 66%. Glucose, pyruvate and lactate concentrations in tubal fluid, measured by microfluorescence assays, were 1.11, 0.14 and 5.4 mM respectively. The concentrations of 17 amino acids in tubal fluid were measured by high performance liquid chromatography following fluorescence derivatization. Arginine (0.19 mM) > alanine (0.11 mM) > glutamate (0.09 mM) were present in highest concentration in all phases of the cycle. All 17 amino acid concentrations in tubal fluid were below those in the vascular perfusate. These data provides the basis for a culture medium whose composition mimics the physiological environment to which early human embryos are exposed.

Adrenergic beta-Agonists↗

Magnetic resonance imaging of the uterus after endometrial resection.

OBJECTIVE: Despite the increasing popularity of endometrial resection for the treatment of menstrual problems, the long term sequelae of this procedure are poorly recognised. As diagnostic hysteroscopy following endometrial resection is frequently unrewarding and transvaginal ultrasound is incapable of detecting subtle changes in endometrial morphology, magnetic resonance imaging was employed to evaluate the uterus. DESIGN: Retrospective study of unselected post-operative women. METHODS: Fifty-nine women, of whom 22 were amenorrhoeic, were studied a mean number of 34 months after endometrial resection, using a 1.5 Tesla magnetic resonance imaging system with a pelvic phased array coil for signal reception. T2-weighted FSE images were acquired through the long and short uterine axis and volumetric assessment of each uterine layer performed using an ISG Allegro workstation. MAIN OUTCOME MEASURES: The location and volume of residual endometrium, the volume of junctional zone and myometrial tissue, and the presence of additional intrauterine and pelvic pathology were recorded. RESULTS: Residual endometrium was demonstrated in all except three amenorrhoeic women, with a similar mean volume present in menstruating and amenorrhoeic groups. Additional findings included adenomyosis, haematometra, fallopian tube dilatation and free intraperitoneal fluid. CONCLUSIONS: The majority of amenorrhoeic and all menstruating women have residual endometrium after endometrial resection. The lack of communication of islands of residual endometrium with the uterine cavity results in haematometra formation, fallopian tube dilatation and possibly free intraperitoneal fluid.

Adult↗

A survey of semen donor attitudes.

Semen donors have been required to register with the Human Fertilization and Embryology Authority since its formation in 1990. Since then many clinics have reported a shortage of donor semen for donor insemination treatment. Is this because potential donors are worried about the protection of their anonymity? No published studies are available concerning the attitudes to semen donation in the UK. It was against this background that an investigation of the attitudes of potential semen donors was carried out. Four dimensions were investigated: (i) motives, (ii) personal detachment and involvement, (iii) detachment and involvement with respect to recipients, and (iv) detachment and involvement with respect to offspring. A total of 55 potential semen donors completed the attitude questionnaire from semen donation programmes in three in-vitro fertilization units. The questionnaire format was found to be an effective method of data collection for this sensitive area of research, and the major findings were (i) 89% of potential donors required confidentiality and guaranteed anonymity; (ii) 82% did not mind providing non-identifying information to the recipients and offspring; (iii) 69% of potential donors expected financial reward; and (iv) 69% did not welcome counselling.

Attitude↗

Assessment of uterine receptivity prior to embryo transfer: a review of currently available imaging modalities.

This article aims to review in detail the current literature concerning the efficacy of, and problems associated with, the use of ultra-sonography and magnetic resonance imaging in predicting uterine receptivity and hence the outcome of assisted conception. Although the quality of the embryo and transportation to the uterine cavity are obvious requirements for in-vitro fertilization/embryo transfer treatment, attention has recently centred on the receptivity of the endometrium to the growing blastula. High resolution ultrasonography is currently the imaging modality of choice, but measurement of endometrial thickness is only associated with successful treatment outcome if ovarian stimulation includes clomiphene citrate. However, the ultrasonographic texture of the endometrium may have a greater prognostic value for implantation. The current literature is relatively unanimous that a 'triple' layered appearance of the uterus is associated with a 23-42% pregnancy rate and that endometrium is unreceptive when iso- or hyperechoic compared with myometrium. In an attempt to improve prediction rates, new techniques including magnetic resonance (MR) imaging are being used to determine uterine receptivity. Early results from MR imaging suggest that in patients treated with standard regimen of GnRHa, followed by human gonadotrophin (HMG), neither the endometrial thickness nor the volume is related to outcome. However, the relative signal intensity of the uterine layers provides good discrimination prior to embryo transfer, between pregnant and non-pregnant groups.

Embryo Transfer↗

Synthetic and biological macromolecules: protection of mouse embryos during cryopreservation by vitrification.

The ability of macromolecules to protect 8-cell mouse embryos during a vitrification protocol was assessed by the comparison of a synthetic macromolecule, polyvinylpyrrolidone (in the form of Percoll), and a biological macromolecule, human serum albumin (HSA). Vitrification solutions, which included glycerol (50% v/v), sucrose (0.75 mol/l) and either macromolecule Percoll (50% v/v) or HSA (1.125% w/v), were found to provide similar rates of survival. Both compounds resulted in a significant reduction in the incidence of disruption to the zonae pellucidae of cryopreserved embryos, to 4.8 +/- 1.3% and 10.3 +/- 1.2% respectively, when compared to the outcome when neither was present in the vitrification solution (20.4 +/- 2.5%; P < 0.01). Polyvinylpyrrolidone in the form of Percoll offers advantages over HSA in this work: it provides a lower rate of zona disruption and avoids the need for screening for pathogenic contaminants such as human immunodeficiency virus and hepatitis B and C.

Animals↗

Magnetic resonance imaging and transvaginal ultrasound of the uterus prior to embryo transfer.

This study was designed to investigate the role of magnetic resonance (MR) imaging in predicting the outcome of in-vitro fertilization (IVF)/embryo transfer treatment by seeking differences in receptive compared to unreceptive endometria. Women about to undergo embryo transfer were submitted to both vaginal ultrasound and MR imaging. Measurements were obtained of the thickness, cross-sectional area and volume of uterine layers and of the MR signal intensity ratios between layers. Measurements were compared with the occurrence of subsequent successful implantation. Although there was no association with either the quantity or the relative signal intensity of the endometrium, an interdependence was demonstrated between both the endometrium/myometrium and myometrium/junctional zone signal intensity ratios and subsequent successful implantation (P < 0.037 and < 0.004 respectively). It is concluded that MR imaging may provide unique information which may help in predicting the outcome of IVF/embryo transfer treatment and in understanding implantation. Significant differences were seen in the relative MR signal intensities of the myometrium.

Adult↗

Age related changes in the female reproductive cycle.

OBJECTIVE: To investigate the effect of age on the control of the reproductive cycle in regularly menstruating women. DESIGN: In this prospective study all women were seen regularly during both the follicular and luteal phases. Ultrasound scanning was used to confirm ovulation and measurements were taken to assess follicular development and endometrial thickness. Serum gonadotrophin levels on day 4 of the cycle, the maximum periovulatory oestradiol and progesterone on the seventh day after ovulation were measured and compared in different age groups. SUBJECTS & SETTING: Fifty-six healthy, regularly menstruating women were recruited from volunteers amongst staff of the University Hospital of South Manchester. RESULTS: Ovulation occurred later in the cycle for older women, with mean follicular phase length increasing from 13.9 days (in group 21-25 years) to 15.9 days (in group 37-45 years (P < 0.05). The mean of the maximum follicular diameter prior to rupture was significantly smaller in the older women: 16.7 mm in the 37 to 45 years old group compared with 19.6 mm, 21.6 mm and 21.3 mm in the 21 to 25, 26 to 31 and 32 to 36 years old age groups, respectively (P < 0.001). The maximum thickness of the endometrium in the luteal phase was greatest for older women: 15.9 mm in the age group 37 to 45 years compared with 12.1 mm in the age group 21 to 25 years (P < 0.001). Serum gonadotrophin concentrations during menses were higher with increased age; mean follicle stimulating hormone was 4.8 iu/l in the age group 21 to 25 years, and 8.5 iu/l in the age group 37 to 45 years (P < 0.001). Mean luteinising hormone was 4.5 iu/l in age group 21 to 25 years and 7.21 iu/l in age group 37 to 45 years (P < 0.001). Mean ovarian steroid concentrations were no different. CONCLUSIONS: These data illustrate significant age related differences in the pituitary-ovarian axis and endometrial thickness. This has implications for the management of older women in assisted reproduction and fertility control programmes.

Adult↗

Eicosanoids and ovulation.

PGs and probably other eicosanoids play a fundamental role in the process of ovulation, more specifically in the mechanism of follicle wall rupture. Although the nature of this role has yet to be established a number of plausible theories exist. It seems likely that altered PG metabolism is responsible for some cases of human female subfertility. The potential for fertility control by PG inhibition is an exciting possibility for the future.

Animals↗