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Biomedical subjects

J Timson

Publications and source records attributed to J Timson.

At least 19 recordsLinked to original sources

Should ICSI be the treatment of choice for all cases of in-vitro conception?

The objective of this study was to examine different clinical scenarios of in-vitro conception, viz. fertilization with conventional IVF, IVF with high insemination concentration (HIC) and intracytoplasmic sperm injection (ICSI), and assess on a sibling oocyte comparison the hypothesis that ICSI should be performed in all cases requiring in-vitro conception. ICSI with husband's spermatozoa had a higher incidence of fertilization as compared with IVF or IVF with HIC with donor spermatozoa (if previous failure of fertilization had occurred) for unexplained infertility. Similarly, ICSI with husband's spermatozoa had as high an incidence of fertilization as IVF with donor spermatozoa for patients with severe oligozoospermia, asthenozoospermia and/or teratozoospermia, even when the spermatozoa were not selected for their morphology. Two studies were performed to assess ICSI in potential oocyte-related failure of IVF, viz. when fertilization occurred in >50% of oocytes for one group of patients, and in <50% of oocytes in a second group. In both of these studies a significant proportion of the oocytes that failed to fertilize with conventional IVF eventually fertilized after ICSI. The overall conclusion was that ICSI as a first option offers a higher incidence of fertilization, maximizes the number of embryos and minimizes the risk of complete failure of fertilization for all cases requiring in-vitro conception. However, among other concerns, current knowledge of ICSI as an outcome procedure does not provide the confidence to use this process in all cases of IVF for the time being.

Female↗

Intracytoplasmic sperm injection (ICSI) versus high insemination concentration (HIC) for human conception in vitro.

The use of high insemination concentration (HIC) for in vitro fertilization (IVF) was compared with intracytoplasmic sperm injection (ICSI) in cases of male factor infertility. Sibling oocytes (n = 252) from 24 patients were used, 123 for HIC and 129 for ICSI. Although the incidence of fertilization was decreased with HIC (48% v. 61%), this treatment was nevertheless a viable option for many patients, especially when ICSI was not available. However, there was a higher incidence of cytoplasmic fragmentation of embryos after HIC compared with ICSI (36% v. 10%, P = 0.003) and the outcome was significantly affected by the severity of teratozoospermia. Using a cut-off of 5% normal forms, the incidence of fertilization with HIC for the group with < 5% normal forms was 37% compared with 72% for the group with > 5% normal forms; there was also a significant decrease in cleavage rate (P = 0.05) and the number of regular embryos (P = 0.005), and an increase in cytoplasmic fragmentation (P = 0.006) in patients with < 5% normal forms. No distinction was made between cases of teratozoospermia when ICSI was used. The present study confirms the value of HIC as a first line treatment for male infertility, as long as ICSI remains significantly more expensive and concerns on safety are mooted. However, the use of sibling oocytes for ICSI is recommended, especially in cases with < 5% normal sperm morphology.

Adult↗

Micro-assisted fertilization in patients who have failed subzonal insemination.

During the past 3 years we have used direct injection of spermatozoa into the cytoplasm of the oocyte (DISCO) in an attempt to procure conception in vitro where subzonal insemination (SUZI) has failed. Acknowledging the paucity of information about this invasive procedure in humans, it was clearly the only alternative for some patients. A total of 58 patients (cycles) who had had previously failed SUZI elected for this approach. Sibling oocytes, where possible, were used as a comparison between DISCO, SUZI, partial zona dissection (PZD) and microdrop in-vitro fertilization (IVF). Fertilization and embryo transfer was achieved by 66% (n = 38) of patients. Patients with embryos derived solely from DISCO (n = 19) produced four clinical pregnancies (21%), four patients had embryo transfer from SUZI embryos only with no pregnancies, and 15 had embryo transfer from a mixture of SUZI and DISCO embryos, with one dizygotic twin pregnancy from a combined SUZI and DISCO embryo transfer (7%). Twins, one male and one female, have been delivered, there has been one miscarriage and two pregnancies are ongoing. Of the 627 oocytes, 251 were used for DISCO and 71 (28%) were fertilized, 296 were used for SUZI and 29 (10%) were fertilized; 70 were used for PZD, two (3%) were fertilized, and none of the 10 undergoing microdrop IVF were fertilized. Of the 58 patients (cycles) 31% (n = 19) had fertilization with DISCO only, 8% (n = 4) with SUZI only, 28% (n = 15) with both SUZI and DISCO, while only one (2%) had fertilization with PZD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Evaluation of 225 patients undergoing subzonal insemination for the procurement of fertilization in vitro.

OBJECTIVE: To evaluate subzonal insemination for the procurement of fertilization in infertile males. DESIGN: The spermatozoa of infertile males was used, where possible, for in vitro fertilization (IVF) and subzonal insemination with the same cohort of oocytes obtained from their partner. SETTING: An individual unit in a general hospital, Clinical Nomentana, Rome, Italy. PATIENTS: Males who had repeatedly failed to achieve conception in vitro by IVF or in whom seminal parameters were unacceptable for IVF were treated. INTERVENTIONS: Two hundred twenty-five transvaginal oocyte retrievals were performed. MAIN OUTCOME MEASURES: The incidence of fertilization, cleavage, and pregnancy was evaluated in relation to the numbers of spermatozoa injected and the individual spermatozoa parameters. RESULTS: Fertilization occurred in 39% of patients and 16% of eggs, and 12 clinical pregnancies were established. Fertilization increased with increasing numbers of spermatozoa injected. Fertilization with subzonal insemination was significantly greater (39%) than after in vitro insemination (6%) (P less than 0.0001). CONCLUSIONS: Subzonal insemination improved the incidence of fertilization in this series of patients, and a new classification of spermatozoa based on total motile count aided prognosis for fertilization.

Adult↗

Caffeine.

Most of the population of the world is exposed to caffeine to a greater or lesser extent since it occurs in a number of plants used in the preparation of widely consumed drinks, and has in addition a limited therapeutic use. Chromosomal abnormalities are induced by caffeine in both plant cells and in mammalian cells in culture and it also has some anti-mitotic activity. DNA-repair processes sensitive to caffeine have been demonstrated in a number of cell systems and it has been shown to affect a wide range of other cellular processes. Caffeine has potent mutagenic effects in Escherichia coli and other micro-organisms both when acting alone and in combination with other mutagens. However its mutagenic activity in Drosophila has been disputed and the available evidence suggests that it is neither mutagenic in mammals nor synergistic with other mutagens although at very high doses it appears to have some teratogenic activity in mammals.

Animals↗

Hydroxyurea.

Hydroxyurea (HU) is an anti-leukaemia and anti-tumour drug which has also found limited application in the treatment of dermatological disorders. It is a potent inhibitor of DNA synthesis in many organisms from viruses to man and in cell culture systems. To a lesser degree it can also inhibit RNA and protein synthesis. It is anti-mitotic and cytotoxic depending on the concentration used, the duration of exposure, and the sensitivity of the organism. In most cells HU is active mainly in the S-phase of the cycle and because of the easy reversibility of its action it has been used as a synchronising agent in cell cultures with some success. There is conflicting evidence about the ability of HU to act as an inhibitor of the natural DNA repair mechanisms in cells exposed to radiation or alkylating agents. HU has, however, been shown to induce chromosome damage in a number of organisms including man. It is clearly teratogenic in mammals and can cross the placental barrier at least in rats and the golden hamster, but it is believed to have only a limited mutagenic activity. Studies involving a direct comparison of the action of HU with other compounds suggest that the = C--NHOH moiety is responsible for its biological activity.

Animals↗

Theobromine and theophylline.

Theobromine and theophylline have a limited therapeutic use and in addition they occur in plants used in the preparation of a number of widely consumed drinks. Thus most of the population must be exposed to both compounds. Chromosome abnormalities are caused by both theobromine and theophylline in plant cells and in mammalian cells in culture, and both have anti-mitotic activity. While they are fairly potent mutagens in Escherichia coli and other lower organisms the rather scanty available evidence suggests that they are not mutagenic in mammals. The difference in mutagenic activity may be due to the reported inability of E. coli to demethylate these compounds, a process which occurs readily in mammals including man. The structure-activity relationships of these compounds are complex but the available evidence suggests that methylation at position 1 is the most important for both mutagenic activity and the anti-mitotic effect while methylation at position 3 is of most importance in the action on chromosomes.

Animals↗

6-thioguanine: antimitotic effect on human lymphocytes in vitro prevented by adenine.

The action of 6-thioguanine on the division of PHA-stimulated human lymphocytes in vitro has been investigated and shown to have a definite antimitotic effect which is prevented by adenine but not by guanine or hypoxanthine. It is suggested that in this test system 6-TG exerts its main inhibitory action on phosphoribosylpyrophosphate amidotransferase.

Adenine↗