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Biomedical subjects

A L Speirs

Publications and source records attributed to A L Speirs.

At least 19 recordsLinked to original sources

A quantitative analysis of the impact of cryopreservation on the implantation potential of human early cleavage stage embryos.

The impact of cryopreservation on the implantation potential of early cleavage stage (day 2) embryos was assessed by analysing the outcome from > 5000 thawed embryos in relation to the outcome from a similar number of fresh embryos. Analysis of procedures in which all transferred embryos fulfilled equivalent defined criteria revealed no significant difference in the implantation rates (fetal hearts/100 embryos transferred) of fresh 4-cell embryos (16.6%) and fully intact thawed 4-cell embryos (16.9%). Although 2-cell embryos implanted at significantly lower rates, there was again no significant difference between fresh (6.5%) and fully intact thawed (7.2%) embryos. Similar analysis of all embryos (irrespective of cell number on day 2) demonstrated that the implantation potential of partially intact thawed embryos was related to the extent of blastomere loss with the implantation rate of embryos with 50% cell survival (5.4%) being approximately half the rate of fully intact embryos (11.3%). Combining the values obtained from 'pure' data for the implantation rates of embryos with defined levels of survival with their relative prevalence in the total population of thawed embryos gave a predicted number of implantations (441) which was similar to the observed outcome (463). This number was approximately 30% less than the number expected had the same embryos been transferred fresh (635). The results suggest that intact thawed embryos have the same implantation potential as equivalent fresh embryos and that the impact of cryopreservation is limited to blastomere loss which is directly related to loss of implantation potential. The observed frequency of blastomere loss results in a reduction of approximately 30% in the implantation potential of a population of embryos following cryopreservation.

Blastomeres↗

Fluorescent study of chromatin and tubulin in apparently unfertilized human oocytes following ICSI.

In this study we examined 138 oocytes which were meiotically mature and, on light microscopic examination, contained either no or one pronucleus following intracytoplasmic sperm injection (ICSI). Oocytes were fixed and simultaneously stained for chromatin (Hoechst 33258) and the spindle (alpha-tubulin antibody). In nine oocytes, no sperm nucleus was observed. The remaining oocytes were separated into two groups following staining; (i) oocytes which had remained at metaphase II after ICSI (n = 74); and (ii) oocytes in which resumption of meiosis was observed after ICSI (n = 55). In all oocytes in which sperm chromatin was absent no resumption of meiosis had occurred and therefore parthenogenetic activation by the process of ICSI seems to be a rare event. In 17 out of 74 (23%) oocytes which remained at metaphase II, staining identified premature chromosome condensation (PCC) of the sperm chromatin (G1-PCC). Sperm nuclear decondensation or further transformation of the sperm chromatin was observed in 56 out of 74 (76%) oocytes which remained at metaphase II after ICSI and in 46 out of 55 (84%) oocytes which had resumed meiosis, indicating that initiation of sperm decondensation is independent of the resumption of meiosis in the oocyte. In contrast, transition of the sperm nucleus beyond the decondensed stage only occurred in association with resumption of meiosis in the oocyte (no pronuclei in metaphase II oocytes). The presence of both male and female pronuclei in 53% of oocytes which had resumed meiosis indicates that changes in sperm chromatin beyond the initial decondensation stage are dependent on cytoplasmic conditions which also permit female pronuclear formation.

Cell Nucleus↗

Intracytoplasmic sperm injection: a major advance in the management of severe male subfertility.

OBJECTIVE: To determine the success of intracytoplasmic sperm injection for severe male infertility. DESIGN: A retrospective survey. SETTING: A tertiary infertility service. PATIENTS AND INTERVENTIONS: One hundred fourteen couples had 119 intracytoplasmic sperm injection treatments because of previous failure of standard IVF, poor results with subzonal insemination, sperm concentration < 2 x 10(6)/mL, other sperm defects, or male genital tract obstruction. MAIN OUTCOME MEASURES: Fertilization, implantation, and pregnancy rates. RESULTS: Of 1,185 oocytes treated by intracytoplasmic sperm injection, normal fertilization and cleavage occurred in 717 of 1,073 that survived (67% normal fertilization rate). Abnormal fertilization occurred in 113 oocytes (11% abnormal fertilization rate) and 112 oocytes did not survive the procedure (survival rate of 90%). In 117 couples, 251 embryos were transferred fresh, 409 embryos were cryopreserved, and 224 were transferred after thawing. The implantation rate was 7.4% (fetal heart per embryo transferred). To date 36 clinical pregnancies have been achieved (12% per fresh transfer, 20% per frozen transfer, and 30% overall), 24 are ongoing or delivered (6% per fresh transfer, 14% per frozen transfer, and 20% per intracytoplasmic sperm injection). The fertilization rates were the same (65%) with various sperm defects but higher with genital tract obstructions (75%). CONCLUSION: Intracytoplasmic sperm injection has improved the prognosis of severe male infertility.

Cytoplasm↗

The use of intracytoplasmic sperm injection for the treatment of severe and extreme male infertility.

The outcome of treatment by intracytoplasmic sperm injection (ICSI) is described for patients with severe male infertility. In 296 consecutive cycles, a normal fertilization rate of 69% was achieved with 288 cycles (97%) resulting in embryos suitable for transfer. A total of 32 clinical pregnancies were achieved from the transfer of fresh embryos (clinical pregnancy rate of 12% per transfer) and an additional 44 clinical pregnancies were obtained after the transfer of frozen-thawed embryos (clinical pregnancy rate of 16% per transfer). Overall, 57 of the 76 pregnancies were ongoing or delivered. An analysis of outcome in 5 male factor subgroups revealed no significant differences in pregnancy and implantation rates between the categories. However, the fertilization rate was significantly lower in patients with oligoasthenoteratozoospermia and significantly higher in those patients for whom epididymal sperm were used for insemination. The treatment of patients with extreme male infertility is also described; normal fertilization and embryo development were obtained using ICSI in patients with mosaic Klinefelter's syndrome, severe sperm autoimmunity, round-headed acrosomeless sperm (globozoospermia), completely immotile sperm selected by hypo-osmotic swelling and sperm isolated from testicular biopsies. Three ongoing pregnancies were obtained from 6 patients for whom testicular sperm were used. These results demonstrate the value of ICSI in the management of severe male infertility, however, the treatment of some types of extreme male infertility using ICSI may be limited.

Autoimmune Diseases↗

When predictions don't predict.

One of the most widespread abuses of statistical methods involves the misinterpretation of statistical significance after the application of multiple comparisons. This paper highlights the problem by demonstrating 'significance' when clearly none exists.

Female↗

Increasing the human menopausal gonadotropin dose--does the response really improve?

This study assesses the effects of attempts to optimize human menopausal gonadotropin (hMG) dosage in 271 patients who had at least two hyperstimulation cycles for in vitro fertilization or gamete intrafallopian transfer. In the first cycle, all patients received clomiphene citrate and hMG 150 IU/d. In the second cycle, the hMG dose was increased in 45% of patients to try to increase the egg yield. In spite of the increase, the population response was practically identical in both cycles. Median numbers of eggs retrieved (6 versus 6), no eggs retrieved (0.4% versus 1%), only one or two eggs retrieved (10% versus 10%), and canceled cycles (10% versus 10.7%). This suggests that increasing the hMG dosage above 150 IU does not increase the number of eggs retrieved. A poor response may be due to inherent differences in follicular development that cannot be overcome by increases in hMG dosage.

Dose-Response Relationship, Drug↗

The fate of supernumerary oocytes in gamete intrafallopian transfer (GIFT) is not predictive of a poor outcome: the effect of oocyte selection.

In 161 consecutive gamete intrafallopian transfer (GIFT) cycles in which supernumerary oocytes were inseminated, a failure to fertilize any of these oocytes was no more predictive of an unsuccessful outcome than the simple overall pregnancy rate in this group. This is possibly related to the significantly reduced proportion of oocytes graded as good in the supernumerary group.

Female↗

Environmental stress factors associated with toddler's diarrhoea.

Seventeen children with toddler's diarrhoea showed significantly higher incidence of environmental and biographical indicators of personal or familial stress than a matched group with other physical disorders. An association is suggested between environmental influences and the aetiology and maintenance of toddler's diarrhoea.

Child, Preschool↗

Analysis of the outcome of in vitro fertilization in relation to the timing of human chorionic gonadotropin administration by the duration of estradiol rise in stimulated cycles.

A retrospective analysis was carried out to assess the outcome of ovarian stimulation on in vitro fertilization when human chorionic gonadotropin (hCG) was administered after 5, 6, or 7 days of continuously rising plasma estradiol (E2). There was no significant difference in the number and size of large follicles in each group although the number of small follicles (less than 15 mm in diameter) decreased significantly after 7 days of E2 rise. After hCG injection in the 7-day group, the E2 level fell below the previous day's value in 40% of patients, whereas a similar fall was observed in only 16% of patients in the 5- and 6-day groups. In those cycles where a luteinizing hormone surge occurred, most surges were detected during the seventh day of E2 rise. The pregnancy rate was 31% when hCG was given after 6 days of rising E2, 21% after 5 days, and 14% after 7 days. In patients achieving pregnancy in the 6-day group, 53% of embryos were derived from leading follicles. In the 7-day group, only 15% of embryos associated with pregnancies were derived from leading follicles. These results strongly suggest that in stimulated cycles, hCG should be administered after 6 days of continuously rising E2. It is therefore postulated that 6 days of rising E2 represents a mean optimal period for follicular growth and oocyte maturation in stimulated cycles.

Chorionic Gonadotropin↗

Aspects of multiple embryo transfer.

Three hundred seventy-two patients underwent laparoscopy for in vitro fertilization and embryo transfer. Of these, 156 were treated with clomiphene citrate alone, 203 with clomiphene citrate and hMG, and 13 with hMG alone. Two-hundred seventy-two of these patients underwent embryo transfer, and 55 pregnancies resulted. Of these, 30 were ongoing, 14 biochemical, 6 ectopic, and 5 aborted. Where four embryos were transferred, the pregnancy rate was found to be significantly higher than when a lesser number were transferred. When the embryos transferred were analyzed, however, it was found that fewer than 10% of all transferred embryos implanted and it was largely a function of multiple embryo transfer per patient that led to success. When the type of hyperstimulation was compared, clomiphene citrate cycles were found to be less successful in that they produced fewer oocytes and embryos than did cycles in which hyperstimulation was achieved by supplementary hMG. It is conceded that this is an overall analysis and that individuals, especially those producing twins, had more than one good embryo transferred into a receptive uterus. The data suggest that unsuccessful cycles had somewhat poorer quality embryos, nonreceptive endometria, or a combination of these factors when compared with those of the successful embryo transfer cycles. The only predictive factor as to outcome relates to the multiplicity of embryos transferred. The fact that some IVF cycles produce multiple pregnancies indicates that a predictor of embryo health is urgently required. However, until such a reliable predictor is obtained, multiple embryo transfer remains a major advance in the success of IVF and ET.

Abortion, Spontaneous↗

Serum supplement in human in vitro fertilization and embryo development.

The effects of maternal preovulatory serum and human fetal cord serum supplement in culture medium in human in vitro fertilization and embryo development were compared in 208 cases over an 8-month period when there were no significant changes in other variables. A significantly higher pregnancy rate was observed in the fetal cord serum group despite no significant difference being found in fertilization and embryo cleavage rates. This suggests a difference in the health of the embryo cultured in different serum supplements.

Blood↗