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Biomedical subjects

C R Kingsland

Publications and source records attributed to C R Kingsland.

At least 19 recordsLinked to original sources

Role of mitotic control in spermatogenesis.

OBJECTIVE: To study the correlation between the incidence of sex chromosome aneuploidies in the somatic cells and spermatozoa in karyotypically normal infertile men and fertile donors. DESIGN: A prospective, phase two, controlled study. SETTING: A teaching Hospital Reproductive Medicine and Medical Genetics Units. PATIENT(S): Ten patients with idiopathic oligozoospermia and 10 sperm donors with proven fertility, all with a normal karyotype 46, XY. INTERVENTION(S): Multicolor fluorescence in situ hybridization (FISH) of peripheral blood lymphocytes and spermatozoa using a probe cocktail containing the alpha satellite DXZ1 for the X centromere, DYZ1 for the heterochromatic region of the long arm of the Y, and cosmids D21S259, D21S341, and D21S342 for Down syndrome critical region of chromosome 21. MAIN OUTCOME MEASURE(S): The incidence of chromosome X, Y, and 21 aneuploidies in peripheral lymphocytes and spermatozoa in both groups. RESULT(S): The incidence of aneuploidies related to chromosomes X, Y, and 21 were significantly higher in peripheral lymphocytes and spermatozoa of infertile men compared with donors. There was a positive correlation between the incidence of chromosome aneuploidies in the somatic cells and sperm in all men. CONCLUSION(S): These findings provide suggestive evidence for the importance of mitosis in spermatogenesis and the role of mitotic instability in unexplained oligozoospermia.

Adolescent↗

Evaluation of the role of mitotic instability in karyotypically normal men with oligozoospermia.

OBJECTIVE: To estimate the incidence of sex chromosome aneuploidies in the somatic cells of karyotypically normal infertile men and fertile donors. DESIGN: A prospective, two-phase, controlled study. SETTING: Reproductive medicine and medical genetics units of a teaching hospital. PATIENT(S): Ten patients with oligozoospermia and 10 sperm donors with proved fertility, all with a normal karyotype 46 XY. INTERVENTION(S): Multicolor fluorescence in situ hybridization (FISH) of peripheral blood lymphocytes using a probe cocktail containing the alpha satellites DXZ1 for the X centromere and DYZ1 for the heterochromatic region of the long arm of the Y and the radiolabeled alpha satellite D18Z1 for chromosome 18. MAIN OUTCOME MEASURE(S): The incidence of sex chromosome aneuploidies in both groups. RESULT(S): A 13-fold increase in sex chromosome aneuploidies was observed in the somatic cells of infertile men with "unexplained" oligozoospermia compared to donors (P=.008). CONCLUSION(S): These findings provide suggestive evidence for the existence of an inherent mitotic instability in men with unexplained oligozoospermia.

Adult↗

Assessment of testicular core temperatures using microwave thermography.

A new method for the reliable assessment of testicular core temperature using microwave technology is presented. This study was designed to assess whether alterations in testicular thermoregulation could be reliably demonstrated in patients with clinically apparent varicoceles (n = 36), in those with idiopathic male infertility (n = 52) and in fertile donors (n = 20) using this new microwave thermographic technique. The measurements obtained were found to be reliable and reproducible. Testicular core temperature measurements were significantly different between the groups (P < 0.001). Furthermore, there was a temperature gradient between the scrotal neck and the testicular core in all groups; testicular core temperatures were lower than scrotal neck temperatures. The magnitude of this temperature difference was also significantly different (P < 0.001) between the groups. Microwave testicular thermography is a new technique that is safe and accurate. Preliminary results suggest altered testicular thermoregulation in a group of patients with impaired spermatogenesis with and without varicocele. Testicular temperature profiles obtained by microwave thermography may be of value in the assessment of infertile men with or without a varicocele.

Adult↗

Human sperm head morphometric distribution and its influence on human fertility.

OBJECTIVE: To study the distribution of live sperm head size in semen and sperm preparations as a predictor of fertility. DESIGN: Prospective blind clinical trial. SETTING: Academic tertiary referral center. PATIENT(S): One hundred fifty-five patients undergoing IVF treatment. Females with conditions negatively influencing fertilization were excluded. INTERVENTION(S): Morphometric analysis (head area, major axis, minor axis, and elongation ratio) of video images of sperm in semen and swim-up preparations used for IVF treatment was performed with a Hamilton-Thorne analyzer V 8.1 (Hamilton-Thorn Research, Beverly, MA). MAIN OUTCOME MEASURE(S): Oocyte fertilization. RESULT(S): Seventy-four percent of patients achieved fertilization. Fertilizers and nonfertilizers had different sperm head area distribution. The fertilizers had a significantly smaller interquartile range of sperm head area and of major axis in both semen and sperm preparation compared with the nonfertilizers. A subgroup of men who had fathered a child naturally had a more uniform sperm head area in semen with a significantly smaller median compared with those who failed to father a child naturally with their healthy female partner. We used multiple logistic regression applying forward stepwise selection of variables in building three predictive models of probability of fertilization. CONCLUSION(S): Successful IVF or history of fathering a child was associated with a more uniform sperm head area in semen and sperm preparation.

Adult↗

The effect of progestagens on the carotid artery pulsatility index in postmenopausal women on oestrogen replacement therapy.

Part of the cardioprotective effect of postmenopausal oestrogen replacement therapy has been attributed to arterial vasodilation. This effect is partially reversed in the uterine artery by the addition of a progestagen. This study was designed to compare the effects of the C21 progestagen, dydrogesterone and the C19 testosterone derivative, norethisterone on the carotid artery pulsatility index (PI) (thought to represent distal impedance to flow) using a randomized double blind cross-over trial. The addition of progestagen resulted in a significant increase in the carotid artery PI from a median value of 1.67 during the oestrogen only phase to 1.77 (P = 0.02) during the combined phase. This trend was seen with both dydrogesterone and norethisterone, but there was no significant difference in the size of the effect caused by either progestagen. The addition of cyclical progestagen to ERT partially antagonizes the reduction in the carotid artery PI.

Carotid Arteries↗

Peritoneal fluid concentrations of interleukin-8 in women with endometriosis: relationship to stage of disease.

There is increasing evidence that immunological mechanisms play a role in the pathogenesis and pathophysiology of endometriosis. It was therefore of interest to study interleukin-8 (IL-8), a chemokine, in the peritoneal fluid and peripheral blood of women undergoing laparoscopic procedures. The presence and concentrations of IL-8 in relation to endometriosis, infertility and abdominal pain were evaluated. Samples of peritoneal fluid (n = 49) and peripheral blood (n = 50) were obtained from 50 consecutive patients undergoing laparoscopic surgery for various gynaecological indications (abdominal pain, infertility, sterilization). IL-8 was present in the peritoneal fluid of most women (87%). The concentration of IL-8 in the peritoneal fluid was higher in women with endometriosis compared to women without (P = 0.02). This difference was more pronounced in early (stage 1) endometriosis (P = 0.001). IL-8 concentrations in the peritoneal fluid were also higher in women with early endometriosis compared to women with later stages of the disease (P = 0.003). Peripheral blood concentrations did not correlate with peritoneal fluid concentrations of IL-8 and/or the presence of endometriosis. We conclude that IL-8 is an important factor that may contribute to the pathogenesis of endometriosis possibly by promoting neovascularization. This information can be a guide in the development of new therapeutic approaches for the treatment of endometriosis.

Abdominal Pain↗

The hypo-osmotic swelling test in recurrent miscarriage.

OBJECTIVE: To determine whether there is any association between sperm membrane integrity as determined by the hypo-osmotic swelling test score and unexplained recurrent miscarriage. DESIGN: Prospective observational study. SETTING: Tertiary referral center for recurrent miscarriage. PATIENT(S): Semen samples from 20 male partners of women who had had three or more first trimester miscarriages of unexplained etiology and semen samples from 20 prospective semen donors of unknown fertility potential. MAIN OUTCOME MEASURE(S): Sperm density, sperm motility, sperm morphology, and hypoosmotic swelling test score. RESULT(S): There was no difference in the median sperm density, the mean sperm motility, or the mean sperm morphology between the two groups. However, the recurrent miscarriage group had a significantly lower hypo-osmotic swelling test score than the control group. CONCLUSION(S): The hypo-osmotic swelling test score is significantly lower in samples from men whose partners have had unexplained recurrent spontaneous abortions. With the exception of cytogenetic abnormalities in peripheral blood karyotype, this is the first study to identify a male factor component in recurrent miscarriage.

Abortion, Habitual↗

Effect of abnormal hypo-osmotic swelling test on fertilization rate and pregnancy outcome in in vitro fertilization cycles.

OBJECTIVE: To assess the value of the hypo-osmotic swelling test in predicting fertilization, pregnancy, implantation, miscarriage, and live birth rates in IVF-ET cycles. DESIGN: Prospective study. SETTING: Academic tertiary referral center for fertility treatment. PATIENTS: Three hundred twenty-six couples having IVF-ET for tubal damage or male factor infertility with the female partner < 38 years of age. INTERVENTIONS: Each male had a hypo-osmotic swelling test performed between 4 and 8 weeks before IVF-ET. MAIN OUTCOME MEASURES: Fertilization, implantation, miscarriage, and live birth rates. RESULTS: Eighty of 326 men had abnormal hypo-osmotic swelling tests. An abnormal test was not associated with lower fertilization rates (odds ratio [OR] = 1.14; 95% confidence interval [CI] = 0.97 to 1.14) or pregnancy rate (OR = 0.98; CI = 0.50 to 1.96). However, although couples with a normal test had a miscarriage rate of 26.9% (14/52), in the group with an abnormal test the miscarriage rate was 50.0% (7/14) (OR = 0.37; CI = 0.09 to 1.49). This resulted in a reduction in the live birth rate from 14.1% in the group with a normal test to 11.8% in patients with an abnormal test (OR = 1.23; CI = 0.45 to 3.87). CONCLUSIONS: The hypo-osmotic swelling test has little value in predicting fertilization in IVF-ET procedures. However, an abnormal test may help predict adverse outcome if pregnancy is achieved.

Abortion, Spontaneous↗

The sperm deformity index: a reliable predictor of the outcome of oocyte fertilization in vitro.

OBJECTIVE: To evaluate a novel expression of sperm morphological parameters, the sperm deformity index, as a predictor of fertilization in vitro. DESIGN: Prospective blind clinical trial. SETTING: Academic tertiary referral center. INTERVENTION(S): Detailed sperm morphological assessment applying strict morphological criteria and a multiple entry technique for an unselected male population undergoing IVF. The sperm deformity index, defined as the average number of deformities per sperm assessed, was calculated. PATIENT(S): One hundred fifty-eight patients undergoing IVF treatment. Females with conditions negatively influencing fertilization were excluded. MAIN OUTCOME MEASURE(S): Fertilization rates and pregnancy. RESULT(S): Seventy-three percent of patients achieved fertilization. Patients achieving fertilization had a significantly higher median proportion of normal forms and a significantly lower median sperm deformity index than the nonfertilizers. The receiver operator characteristic (ROC) curves identified cutoff points that maximized the sum of sensitivity and specificity at sperm deformity index 1.6 and normal forms 4%. The sperm deformity index had a greater sensitivity (96%), specificity (72%), positive predictive value (90%), and negative predictive value (86%) than the proportion of normal sperm morphology (87%, 69%, 89%, 66%, respectively) at the optimal cutoff points. The area under the ROC curve was greater for the sperm deformity index (0.875) than for the proportion of normal sperm morphology (0.622). Achieving pregnancy did not correlated with sperm morphology. CONCLUSION(S): The sperm deformity index is a more reliable predictor of the outcome of fertilization in vitro than the proportion of normal sperm morphology and can assist to identify patients who require techniques such as intracytoplasmic sperm injection.

Adult↗

Effects of sperm activity on zinc and fructose concentrations in seminal plasma.

Attempts to correlate zinc and fructose concentrations in seminal plasma with andrological parameters have produced inconsistent results. To assess further this relationship, a prospective study was performed measuring zinc and fructose concentrations in seminal plasma in 1178 patients referred for fertility treatment. Seminal analysis was performed with biochemical measurements of seminal zinc and fructose. The main outcome measures were the correlation between motile sperm concentration and seminal zinc and fructose concentrations. Zinc concentrations were not influenced by the motile sperm concentration (r = 0.039). Fructose concentrations were found to be negatively correlated with motile sperm concentration (r = 0.062). We conclude that seminal plasma zinc is an unreliable marker of spermatogenic activity. While there does appear to be a negative correlation between seminal plasma fructose concentrations and motile sperm concentration this relationship is far from linear. Due to the biochemical complexity of seminal fluid attempts to perform such simple correlations between seminal plasma components and andrological parameters are likely to produce inconsistent results and their role in the assessment of sperm function must therefore be called into question.

Adult↗

Successful pregnancy following oocyte donation in a patient with Diamond-Blackfan syndrome and premature ovarian failure.

Diamond-Blackfan anaemia (DBA) is a rare congenital condition characterized by profound anaemia associated with an absence of red cell precursors on bone marrow examination. This report represents the first case of pregnancy following egg donation in a patient with DBA and premature ovarian failure. The patient was a 24 year old woman who had been diagnosed with DBA when aged 6 months. Shortly after menarche, the patient became amenorrhoeic and was diagnosed as suffering from premature ovarian failure. She was entered onto an assisted conception programme and conceived after one cycle of egg donation. The pregnancy was characterized by a gradual decline in haemoglobin concentration, reaching a low of 8.1 g/dl, necessitating a single blood transfusion at 29 weeks of gestation. The patient suffered preterm rupture of the membranes at 29 weeks gestation and was delivered by emergency Caesarean section at 30 weeks of gestation because of chorioamnionitis and breech presentation. Comparing this case with other reports of pregnancy in patients with DBA, our patient suffered a less dramatic fall in haemoglobin concentration and required only a single blood transfusion. It is suggested that because the pregnancy arose from donated genetic material, this may have conferred some protective effect.

Adult↗

Exaggerated effects of progestogen on uterine artery pulsatility index in Turner's syndrome patients receiving hormone replacement therapy.

OBJECTIVE: To investigate the effect of estrogen and progestogen on the resistance to blood flow in the uterine arteries of Turner's syndrome patients. DESIGN: Prospective clinical study. SETTING: A tertiary infertility clinic. PATIENTS: Five Turner's syndrome patients, six patients who had surgical castration, and five patients with idiopathic primary ovarian failure. INTERVENTIONS: The patients were treated with 2 mg E2 valerate to which 500 micrograms norgesterel was added for 10 days in a 28-day cycle. Transvaginal color Doppler was used to measure pulsatility index in the uterine arteries at eight regular intervals during a single cycle. MAIN OUTCOME MEASURE: Pulsatility index of the uterine arteries. RESULTS: The administration of norgesterel to Turner's syndrome patients resulted in an increase in pulsatility index that was significantly higher than in patients who had surgical castration (confidence interval = 0.17 to 2.42). CONCLUSION: The uterine arteries of Turner's syndrome patients are more sensitive to the tonic effect of progestogen. If manifest in cardiac arteries also this phenomenon may be partly responsible for the increased incidence of cardiovascular disease and shorter life expectancy in Turner's syndrome patients. To achieve optimal protection from cardiovascular disease, Turner's syndrome patients may benefit from hormone replacement treatment containing altered doses of estrogen and progestogen.

Arteries↗

Trizygotic quadruplet pregnancy following in-vitro fertilization: an additional factor against replacement of three embryos in young patients?

A study of a 25 year old woman with a previous history of tubal damage, ectopic pregnancy and unsuccessful tubal surgery is reported. Following in-vitro fertilization (IVF) treatment, four viable fetuses were revealed by ultrasound scan at 10 weeks gestation. Two shared the same gestational sac, thus establishing a trizygotic quadruplet pregnancy. The implications of monozygotic twinning in humans are discussed. It is concluded that embryo splitting and its consequences should be seriously considered when multiple embryo transfer in young patients is contemplated.

Adult↗