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Biomedical subjects

D M Saunders

Publications and source records attributed to D M Saunders.

At least 73 records · Page 4Linked to original sources
PubMed1987

Oocyte pickup by laparoscopy replaced by transvaginal aspiration in an in vitro fertilization program.

The results of laparoscopic (lap) and transvaginal (TV) oocyte pickups (OPUs) performed concurrently for in vitro fertilization in 232 consecutive treatment cycles have been reviewed. The patients were compared for age, preoperative estradiol concentration, luteal-phase support, and number of follicles aspirated and were found to be similar but were not matched for cause of infertility. The lap OPU group had more oocytes recovered per follicle aspirated (P less than 0.001), but because of a lower fertilization rate (P less than 0.01), the number of embryos transferred was similar. Nevertheless, more (P less than 0.05) pregnancies occurred in the TV OPU group. Patients were subgrouped so that comparisons of patients with the same cause of infertility, tubal disease alone, were considered. This showed that the pregnancy rate was still higher in the TV OPU group (P less than 0.05). TV OPU was less painful and not associated with increased morbidity, and since the data suggest that TV OPU was at least as successful as lap OPU, it is recommended that all oocyte pickups in the future be performed transvaginally.

Adult↗
PubMed1987

Potential role of pregnancy-associated plasma protein-A in human reproduction.

By radioimmunoassay, pregnancy-associated plasma protein-A (PAPP-A) was undetectable in matched follicular and luteal phase serum samples (n = 17) or in the peripheral circulation of normal males (n = 17). However, seminal plasma (91.5%), cervical mucus (100%) and pre-ovulatory follicular fluid (99.6%) were consistently PaPP-A positive. In addition to PAPP-A, four circulating protease inhibitors (PIs) were detected in pooled seminal plasma whereas pooled follicular fluid contained an additional six. Follicular concentrations of serum PIs were inversely related to molecular size. By contrast, PAPP-A formed a positive concentration gradient across the blood-reproductive tract barrier suggesting PAPP-A production within the reproductive tract. A minor proportion (1.7%) of ejaculated spermatozoa were coated with PAPP-A, as demonstrated by direct immunofluorescence. Since PAPP-A specifically inhibits leucocyte elastase, it is suggested that PAPP-A coated spermatozoa were "selected" to overcome localized phagocytic-proteolytic degradation. The physiological significance of these findings are discussed in relation to human reproduction.

Cervix Mucus↗
PubMed1987

Use of a bioassay for embryo-derived platelet-activating factor as a means of assessing quality and pregnancy potential of human embryos.

The production of an embryo-derived platelet-activating factor (PAF) was recently shown to have a correlation with embryo quality and viability. The detection of this factor was used as a means of examining the effect of various aspects of the in vitro fertilization and embryo transfer procedure on human preimplantation embryo quality. Embryos that resulted in pregnancy produced significantly higher levels of embryo-derived PAF in vitro than embryos that failed to result in pregnancy. Of a further 85 embryos, 43% had a level of embryo-derived PAF that fell in the same range as the embryos that resulted in pregnancy. The production of embryo-derived PAF was related to the type of treatment used to induce follicular development (with clomiphene citrate and human menopausal gonadotropin commencing on day 5 giving best results); the size and estradiol production of the follicles producing the embryo; the age of the embryo culture medium; and the morphology and cell number of the embryos.

Biological Assay↗
PubMed1987

The role of chlamydial antibodies in an in vitro fertilization program.

The reported incidence of antibodies to Chlamydia trachomatis in patients attending infertility clinics is at least 30%. It has been reported that chlamydial antibodies are associated with decreased pregnancy rates following in vitro fertilization (IVF). A study was performed to investigate the significance of chlamydial antibodies in an established IVF program. The results did not show a decreased pregnancy rate in the presence of chlamydial antibodies. Of the women achieving pregnancy, 41% were seropositive compared with 38% seropositivity in women who did not become pregnant. There was no apparent benefit of the use of prophylactic antibiotics. The results also suggested that past infection with C. trachomatis in men did not adversely affect semen analysis or fertilization.

Antibodies, Bacterial↗
PubMed1987

Production of pregnancy-associated plasma protein-A (PAPP-A) by cultured tumour granulosa cells.

Ten ovarian and 2 cervical tumour cell lines were analysed for the production of pregnancy-associated proteins. Pregnancy-associated plasma protein-A (PAPP-A) was detected by radioimmunoassay in culture media of 2 out of 4 (50%) tumour granulosa cell lines (mean = 104 microIU/10(5) cells/24 h) but not in any ovarian (n = 6) or cervical (n = 2) tumour cell lines. By contrast, human chorionic gonadotrophin (hCG), pregnancy specific beta 1-glycoprotein and alpha-fetoprotein (AFP) were not detected in any of the PAPP-A positive media. Only two cell lines produced hCG (58.5 and 25.5 mIU/10(5) cells/24 h). No AFP was produced by any of these 12 cell lines, whereas placental protein 5 was positive in 7. None of these proteins were detected in the culture media of 4 cell lines. In vitro derived PAPP-A was immunologically indistinguishable from either pregnancy or ovarian follicular PAPP-A. All PAPP-A species interacted reversibly with immobilised heparin and were determined by molecular sieve chromatography to have an apparent molecular weight of 820,000 daltons. Cultured tumour granulosa cells specifically synthesised and secreted a large protein which was immunologically and physicochemically indistinguishable from in vivo (pregnancy and ovarian follicular) derived PAPP-A.

Female↗
PubMed1986

Potassium regulation and progesterone-aldosterone interrelationships in human pregnancy: a prospective study.

Little is known about the intrinsic renal and hormonal regulation of potassium excretion in pregnancy despite major alterations in many of the potassium regulatory factors. Forty primigravid women on an unrestricted diet were studied during the second and third trimesters and exhibited constant absolute and fractional potassium excretion despite a significant increase in plasma aldosterone concentration between these stages. The plasma progesterone level rose significantly between studies but closer analysis showed no correlation between individual changes in plasma aldosterone concentration and progesterone between trimesters. In the 14 subjects studied post partum, baseline absolute potassium excretion was not significantly altered but filtered potassium fell and fractional potassium excretion tended to rise. After dietary sodium manipulation at these stages, absolute potassium excretion, fractional potassium excretion, and progesterone were unaltered despite significant changes in plasma aldosterone concentration and sodium excretion. These results suggest that potassium excretion is held constant throughout pregnancy and that renal tubular potassium reabsorption adjusts appropriately to the increased filtered potassium load. Progesterone does not appear to be involved in the acute regulation of potassium or sodium excretion but may have effects on sodium and potassium excretion that are constant, proportional to its placental production, and unresponsive to endogenous changes in mineralocorticoid production.

Aldosterone↗
PubMed1986

Failure of implantation in human in vitro fertilization and embryo transfer patients: the effects of altered progesterone/estrogen ratios in humans and mice.

Daily blood samples were taken for progesterone (P) and estradiol (E2) measurements from women who showed a platelet response consistent with the presence of viable embryos after in vitro fertilization and embryo transfer procedures. A comparison of steroid levels between those women who became pregnant and those who did not revealed the following: at and after the time of transfer, women who failed to become pregnant had significantly higher E2 levels and a lower ratio of P/E2 than women who became pregnant. The P/E2 ratio was a better predictor of implantation failure than was the absolute level of either hormone. Experiments were done in mice to test the hypothesis that P could protect implantation of the embryo against the inhibitory effects of high E2. In mice, implantation was inhibited by relatively high levels of E2. This effect was overcome by concomitant administration of P. There was a significant dose-response-related interaction of P with the E2.

Animals↗
PubMed1986

An experience of laparoscopic and transvesical oocyte retrieval in an in vitro fertilization program.

Successful pregnancies have been achieved after in vitro fertilization of oocytes obtained by an ultrasound-guided transvesical approach, as well as with the traditional laparoscope. With the use of the same laboratory facilities, success rates for each retrieval method were evaluated in an established in vitro fertilization program. There was a significantly increased cancellation rate and a decrease in oocyte/follicle rate in the transvesical group, but there was a greater fertilization rate with possible improved embryo quality. Although the transfer rates were similar, the pregnancy rate appeared lower in the transvesical group. A valid comparison of these data is not possible because the two groups are dissimilar for factors known to influence oocyte development and recovery. Different criteria were applied to patient selection and treatment, and operation expertise differed between the two groups.

Embryo Transfer↗
PubMed1986

The effect of cyclical hormonal changes on erythrocyte electrolyte transport mechanisms.

Electrolyte transport characteristics were examined in erythrocytes from 13 normal men and from two groups of women: taking combined oral contraceptive preparations (O/C, n = 10), and ovulatory women (non-O/C, n = 10) pre- and post-ovulation, at the same time intervals (days 7-10 and days 15-18) during a menstrual cycle. With rubidium (86Rb+) used as a potassium analogue, co-transport (ouabain-resistant, frusemide-sensitive 86Rb+ influx) values were found to be lowest in non-O/C women (28 +/- SE 2.5 nmol h-1 10(-9) cells) and highest in men (56 +/- 5.7, P less than 0.001), with results between the two in women taking O/C (42 +/- 4.2, P less than 0.05 vs men, P less than 0.01 vs non-O/C). Passive 86Rb leak (frusemide-and ouabain-resistant) was significantly lower in men (13 +/- 1.6 nmol h-1 10(-9) cells) than in both groups of women (non-O/C 29 +/- 1.8, P less than 0.001; O/C 25 +/- 1.2, P less than 0.001). There was no cyclical variation within either group of women. Maximum ouabain binding (number of NA+,K+-ATPase units) was the same in all groups. Na+,K+-ATPase activity, as determined by ouabain-sensitive 86Rb influx, was the same in men and non-O/C groups, but was significantly suppressed in O/C compared with both men (P less than 0.01) and non-O/C women (P less than 0.05). The differences found were not due to alterations in either progesterone or aldosterone, but could represent an androgenic effect in vivo of the 19-nortestosterone derivatives in combined oral contraceptive preparations.

Adult↗
PubMed1985

Maternal blood platelet physiology and luteal-phase endocrinology as a means of monitoring pre- and postimplantation embryo viability following in vitro fertilization.

The discovery that the fertilized mouse ovum triggers an increased demand for platelets and results in thrombocytopenia during the preimplantation phase of pregnancy provides a monitor for embryo survival and viability. This paper reports a study in which the platelet count was significantly reduced throughout the human preimplantation phase of pregnancy and returned to normal following embryo implantation. The human embryo was shown to produce a platelet activating factor in vitro which caused the reduction in platelet count after embryo transfer. This factor in the embryo culture medium could be measured using a bioassay which provided a means of assessing embryo viability prior to transfer. Some women showed no reduction in platelets after transfer. These embryos failed to produce a platelet activating factor in vitro and pregnancy was not established. Other women displayed a reduction in platelets following transfer but failed to become pregnant. All of these women had elevated luteal-phase plasma E2 levels compared to pregnant patients, which may have interfered with the implantation process. Our observations provide a possible rapid and simple means for monitoring the viability of human embryos cultured in vitro and the survival of embryos in utero.

Blood Platelets↗
PubMed1985

Monitoring of postimplantation embryo viability following successful in vitro fertilization and embryo transfer by measurement of placental proteins.

Serum levels of pregnancy-associated plasma protein A (PAPP-A), human chorionic gonadotropin (hCG), and pregnancy-specific beta 1-glycoprotein (SP1) were measured in 21 women after successful in vitro fertilization and embryo transfer. Of the 21 pregnancies, 14, including 1 twin gestation, progressed successfully to term. The remaining seven, composed of tubal (n = 3), anembryonic (n = 1), and spontaneously aborted (n = 3) pregnancies, failed during the first half of pregnancy. Placental protein measurement was of no diagnostic value in the detection of anembryonic pregnancy. Similarly, measurement of hCG and SP1 could not readily distinguish tubal ectopic from normal intrauterine pregnancies. By contrast, the predictive value (38.9%) of a depressed PAPP-A level in conjunction with superior diagnostic sensitivity (70%) and relative risk factor (23.6) proved to be of greater diagnostic value in this potentially lethal condition. In the absence of ultrasonography, the biochemical diagnostic indices were comparable in the prediction of spontaneous abortion. However, in the presence of a live fetus, PAPP-A levels were consistently depressed (sensitivity, 91.7%) many weeks before pregnancy demise. The relative risk factor of depressed PAPP-A levels was 29 times greater than the risk associated with a depressed hCG level. These findings further demonstrate the potential diagnostic value of PAPP-A measurement for monitoring postimplantation embryo viability.

Abortion, Spontaneous↗
PubMed1985

Placental proteins in the diagnosis and evaluation of the "elusive" early pregnancy.

For many many years much time and effort has been invested to identify, purify, and quantify markers of significant reproductive events. The search for such markers has been recently intensified with the widespread acceptance of IVF and ET as a treatment regimen for the management of certain causes of infertility. Now it is possible to monitor ovarian folliculogenesis and time of ovulation, successful fertilization, and subsequent nidation and the ensuing pregnancy. Following successful fertilization and zygote development, EPF, a protein complex which suppresses in vitro lymphocyte rosette formation can be detected within 24 hours. Shortly after implantation hCG can be measured in the maternal circulation. The developing trophoblastic tissue continues to synthesize and secrete into the maternal circulation many varied proteins including SP1, PAPP-A, and PP5. To date hCG is the mainstay of rapid and early pregnancy diagnosis and is an accepted biochemical marker of successful implantation and trophoblastic activity. Combination of hCG and EPF measurement offers the clinician new insight into his infertile patient for now it is possible to monitor successful fertilization and implantation as separate independent events. Such diagnostic assays should also provide new insight into early embryo mortality rate at the pre- and postimplantation stage and hence indicate the selection pressures acting on an embryo. It is the application of these assays which has led to the definition of subclinical abortions and to the description of biochemical pregnancies. The value of these proteins for the management of compromised early pregnancies has to be more fully examined. Although the differentiation between a normal and abnormal pregnancy is more readily ascertained by serial sampling and analysis of the time taken for circulating levels to double (3). Preliminary data suggest the potential of EPF and PAPP-A measurement in such clinical conditions is enormous. Our studies suggest that PAPP-A, at present, is the only biochemical marker which can predict pregnancy abortion, even in the presence of normal ultrasound scans, many weeks prior to the event, thus implying a vital biological role for PAPP-A in normal pregnancy (52). Despite the need for more intensive evaluation of these early pregnancy indicators the search for that "demmed elusive" marker has more than "Those Frenchies" earnestly looking for him here and there.

Abortion, Threatened↗
PubMed1985

Pregnancy-associated plasma protein-A and placental protein 5 in human ovarian follicular fluid.

By sensitive and specific radioimmunoassays PAPP-A and PP5 were detected in follicular aspirates obtained from women undergoing ovarian hyperstimulation for oocyte harvest prior to in vitro fertilization and embryo transfer. Follicular and pregnancy-derived PAPP-A were immunologically and physicochemically indistinguishable. Similarly, pregnancy- and nonpregnancy-derived PP5 were immunologically indistinguishable. However, in addition to the 18- and 36-K species, a larger species having a molecular size greater than 140K was found in the follicular fluid. Mean follicular PAPP-A and PP5 concentrations were 727 mIU/L and 1376 mAU/L, respectively, with no significant correlation between follicular PAPP-A, PP5, and steroid concentrations. There was, however, a significant but negative relationship with follicular volume. Preliminary in vitro studies indicated that both proteins were synthesized by granulosa cells in preparation for follicular rupture. Follicular PP5, like antithrombin III, interacted reversibly with heparin and thrombin affinity matrices, suggesting a potential biological role as a follicular anticoagulant, whereas PAPP-A, a specific and potent inhibitor of leukocyte elastase, contributes to the maintenance of proteolytic homeostasis and the protection of spermatozoa and embryo against proteolytic attack originating from the maternal leukocytes.

Culture Media↗
PubMed1985

Pregnancy-associated plasma protein-A and placental protein 5 in human seminal plasma.

Human seminal plasma contains two glycoproteins which are physiochemically and immunologically indistinguishable from pregnancy-associated plasma protein-A and placental protein 5. Seminal concentrations of both glycoproteins did not correlate with clinical assessment of semen quality. Furthermore, analysis of split ejaculates indicated a nontesticular origin for both proteins, which are possibly secreted into the distal portions of the tract by the accessory glands (prostate gland and seminal vesicles). The physiological significance of these findings has yet to be determined. However, it is suggested that pregnancy-associated plasma protein-A, a known potent inhibitor of leukocyte elastase, protects the deposited sperm against proteolytic attack originating from the localized leukocyte reaction within the female reproductive tract, thus contributing towards sperm survival within this immunologically hostile environment and enabling fertilization to occur.

Drug Stability↗