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Biomedical subjects

D M Saunders

Publications and source records attributed to D M Saunders.

At least 91 records · Page 5Linked to original sources

Monitoring of postimplantation embryo viability by measurement of PAPP-A, SP1, and hCG.

After successful in vitro fertilization and embryo transfer, chorionic gonadotropin, pregnancy-specific beta 1-glycoprotein, and pregnancy-associated plasma protein-A were measured in serum samples collected serially from 21 patients. While 14 pregnancies, including one twin pregnancy, progressed successfully to term, the remaining seven pregnancies failed during the first half of gestation. This latter group consisted of three tubally implanted, one anembryonic, and three spontaneously aborted pregnancies. Circulating levels of hCG, SP1, and PAPP-A in the patient with an anembryonic pregnancy were within normal limits. Similarly, 90.5% of the serum samples obtained from women with tubal pregnancies showed hCG levels within normal limits. By contrast, only two of these samples had detectable PAPP-A, of which only one was within normal limits. Of the samples obtained from the patients who spontaneously aborted, including one patient with normal ultrasonic findings up to 48 hours prior to the event, 85.7% had PAPP-A concentration below the 10th percentile, whereas only 16.7% of these samples showed depressed hCG levels. These data suggest that PAPP-A measurement has great clinical potential in the management of compromised early pregnancies.

Abortion, Spontaneous↗

The influence of pergonal on in vitro production of placental protein 5 (PP5) by ovarian tumour cells.

A radioimmunoassay for the measurement of placental protein 5 (PP5) has been developed using a second antibody-polyethyleneglycol method to separate free from bound ligand. PP5 immunoreactivity was detected in culture media from a cell line derived from a small cell carcinoma of the ovary (SCCWm2). The culture-derived PP5 shares immunological identity with pregnancy and ovarian follicular PP5. Affinity interactions between PP5 and matrices such as heparin or thrombin-Sepharose were similar and independent of the origin of PP5. PP5 was heterogeneous with two forms, a monomer (18k) and dimer (36k) being detected in all biological fluids examined. The dimer was predominant in ovarian follicles and the SCCWm2 cell line, while the monomer predominated in pregnancy serum. The basal rate of PP5 secretion by the SCCWm2 cell line was 0.61AU/24h/10(5) cells. Incubation of cells in the presence of 150mIU Pergonal stimulated PP5 production 20.6 fold and following removal of Pergonal the production rate was maintained at 18.0 times the basal rate. No choriconic gonadotrophin, pregnancy-specific beta 1-glycoprotein, pregnancy associated plasma protein-A or alpha fetoprotein was detected in the culture medium of the SCCWm2 cell line.

Carcinoma, Small Cell↗

Circulating and tissue concentrations of pregnancy-associated plasma protein-A (PAPP-A) in tubal ectopic gestation.

Concentrations of pregnancy-associated plasma protein-A (PAPP-A), human chorionic gonadotrophin (hCG) and pregnancy specific beta 1-glycoprotein (SP1) were measured by radioimmunoassay in 164 serum and 29 tissue samples obtained from 87 non-pregnant and 29 pregnant women with either tubal (n = 16) or intrauterine (n = 13) pregnancies. Of the 47 serum samples obtained from patients with a tubal pregnancy only two were positive for PAPP-A, whereas in excess of 94% of the samples were positive for both hCG and SP1. Serial measurements of hCG, and SP1, demonstrated an apparently normal growth rate for the tubally implanted trophoblast for the first 6 weeks of pregnancy. Thereafter, the tubal trophoblast is compromised since the tissue content of PAPP-A and hCG was significantly lower than that in intra-uterine derived trophoblastic tissue. By contrast, the content of both PAPP-A and hCG was significantly greater in the trophoblastic, both intra or extra-uterine derived, than in the endometrial/decidual, tissue. Furthermore, the absence of immunoreactive PAPP-A and the severely depressed circulating levels of PAPP-A in women with tubal pregnancies can be attributed to diminished secretion of PAPP-A into the maternal circulation. Therefore, in conjunction with a positive pregnancy test and the patient's clinical history, a severely depressed or absent serum PAPP-A level may aid in the diagnosis of extrauterine pregnancy.

Chorionic Gonadotropin↗

Pregnancy-associated plasma protein A in human ovarian follicular fluid.

Human ovarian follicular fluid contains pregnancy-associated plasma protein A (PAPP-A) immunoreactivity as detected by RIA. This PAPP-A was found to be stable to repeated freeze-thaw cycles and not removed by dialysis. Further characterization showed that ovarian follicular PAPP-A bound reversibly to heparin-Sepharose. On gel chromatography follicular PAPP-A coeluted with radioiodinated PAPP-A and pregnancy serum PAPP-A which was determined to have an apparent mol wt of 820,000. In the RIA, serial dilutions of high molecular weight heparin-Sepharose binding proteins gave parallel displacement curves to pooled late pregnancy serum and to the International Reference Preparation, WHO 78/610. All the human ovarian follicular fluids tested had PAPP-A concentrations between 0.317-1.595 IU/liter. The relationship between follicular content of PAPP-A and follicular volume was best expressed by the exponential relationship, y = 164.3 e0.117x. Therefore, ovarian follicular fluid PAPP-A has many physico-chemical similarities to and shares immunological identity with pregnancy-derived PAPP-A. As this pregnancy-associated glycoprotein cannot be detected in the circulation of normal non-pregnant adults, its presence within the Graafian follicle is believed to be of intrafollicular origin for the maintenance of proteolytic homeostasis.

Chromatography, Affinity↗

Ultrasonic signs of imminent ovulation.

Two consistent signs of imminent ovulation in the Graafian follicle have been identified using ultrasound. These signs are a line of decreased reflectivity around the follicle and a crenation pattern within the follicle. The signs may be useful in programs such as in vitro fertilization and artificial insemination, in which timing of ovulation is critical.

Female↗

The prediction of pregnancy failure by measurement of pregnancy-associated plasma protein A (PAPP-A) following in vitro fertilization and embryo transfer.

Circulating PAPP-A was measured serially in five patients following successful IVF-ET. PAPP-A concentrations were consistently normal in all three patients in whom pregnancies progressed normally to term. Depressed levels of PAPP-A were observed in one patient who miscarried spontaneously at 17 weeks' gestation despite ultrasound evidence of normal fetal development. Circulating PAPP-A was not detected in the fifth patient, whose tubal pregnancy ruptured at 8 weeks. These data are discussed in relation to surveillance of pregnancies following IVF-ET.

Abortion, Spontaneous↗

In vitro fertilization and the surgeon.

The recent successes with in vitro fertilization and embryo transfer in the management of female infertility have ramifications outside of gynaecology. Procedures of a general surgical nature in young women should be carried out with possible future oocyte aspiration via the laparoscope kept in mind.

Embryo Transfer↗

Reduced pregnancy rates in AID women with unsuspected ovulatory failure.

A review over five years of 232 patients attending an artificial insemination by donor (AID) clinic was undertaken in order to detect abnormalities in ovulation patterns. Ovulation was determined by luteal phase progesterone estimations. Unexpected anovulation was found in 36% of the patients attending despite an apparently normal previous menstrual history and investigations. This group consisted of 22% who were anovulatory from commencement in the programme and 14% who became anovulatory during treatment. The cumulative pregnancy rates at 15 months for these two groups were lower (73% and 55%) than that for the remaining patients who ovulated normally (90%). A proportion (16%) of the latter group were receiving clomiphene therapy for anovulation recognized before entering the programme. The lower pregnancy rate could not be related to other factors influencing conception and occurred in spite of clomiphene therapy. These results should assist in advising patients on their chances of conception, preventing early discouragement but not encouraging long term insemination which may not improve the pregnancy rate.

Anovulation↗

Effects of clomiphene administration on ovarian function as measured by estradiol and ultrasound.

The growth and rupture of the graafian follicle were studied in 23 women during 40 cycles (20 spontaneous, 20 clomiphene-induced) by the estimation of plasma estradiol levels and ultrasound scan. The mean preovulatory estradiol peak level was 415 pg/ml in spontaneous cycles and 626 pg/ml after clomiphene administration when one follicle was present. Ultrasonic examination revealed the presence of more than one developing follicle in one of 20 spontaneous cycles, and in 11 of 20 cycles after clomiphene treatment. The determination of follicle size and number by ultrasound scan during ovulation induction by the routinely used starting dosage of clomiphene has revealed a previously unrecognized incidence of ovarian overstimulation, and may allow the rationalization of ovulation induction regimens.

Clomiphene↗

The value of ultrasound, gonadotropin, and estradiol measurements for precise ovulation prediction.

The exact prediction of ovulation is becoming more important in the management of infertile women. Graafian follicle diameter, measured by ultrasound and plasma follicle-stimulating hormone, luteinizing hormone, and estradiol levels were compared retrospectively as predictors of ovulation in 14 normal women in whom ovulation was dated by conventional ultrasound techniques. Follicle diameter was found to be a better predictor of the anticipated time of ovulation than endocrine estimations for short-term as well as long-term predictions in normal women. The relationship between follicle diameter and plasma estradiol for each day before ovulation was linear but contained a great amount of scatter, suggesting that the assessment of normality of follicular development in infertile women may not be possible with the use of these parameters.

Estradiol↗

Radioimmunoassay for pregnancy-associated plasma protein A.

A specific and highly sensitive radioimmunoassay for determination of pregnancy-associated plasma protein A in human serum is described. The minimum detection limit for this protein was 2.9 micrograms/L. The within- and between-assay coefficients of variation were 4.0 and 4.5%, respectively. The circulating protein was detected within 32 days of conception in eight normal pregnancies and within 21 days in a twin pregnancy. Circulating concentrations in the mother at term were consistently higher (10-fold) than in matched amniotic fluid; none was detected in the umbilical circulation. This protein was also detected in the circulation of patients with hydatiform mole. This assay will permit investigations into the clinical evaluation of measurements of the protein during early pregnancy and trophoblastic disease.

Amniotic Fluid↗

The outcome of artificial donor insemination compared to the husband's fertility status.

One thousand, three hundred and fifty-seven women were treated by artificial donor insemination (AID) using frozen semen at seven Australian centres. Eight hundred and forty-three of the husbands were azoospermic and five hundred and fifteen had pathological semen. The wives of azoospermic men had a significantly higher rate of success when the two groups were compared by life table analysis. It appears likely that the wives of oligospermic men who require AID are less fertile, and may be a contributory factor in the couple's subfertility.

Australia↗

Artificial insemination by frozen donor semen: results of multicentre Australian experience.

A total of 5461 insemination cycles with frozen donor semen has been analysed for 8 of the larger AID services in Australia. Cumulative pregnancy rate, calculated by life-table analysis, showed that 50% of all patients are pregnant after 6 cycles of insemination and 64% of all patients are pregnant after 12 cycles of insemination. Pregnancy rate was significantly higher in the first 3 cycles, declined in the next 3 cycles and was further reduced in the last 6 cycles of insemination. An average of 10% of all insemination cycle were anovular, but the proportion of anovular cycles was significantly lower in the first 2 cycles of insemination. There was no significant difference in cumulative pregnancy rates over the first 6 cycles of insemination in clinics using cervical mucus scoring or LH assay for detection of ovulation. An average of 12% of all pregnancies obtained by AID resulted in miscarriage.

Australia↗