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Biomedical subjects

D T Baird

Publications and source records attributed to D T Baird.

At least 199 records · Page 11Linked to original sources
PubMed1988

A comparison of dosages of norethisterone for synchronization of cycles in a fixed regimen of follicular augmentation and in vitro fertilization.

Twenty-four patients undergoing elective laparoscopic sterilization were randomized in a fixed schedule of follicular augmentation, oocyte recovery, and in vitro fertilization (IVF) using either 2.5 or 10 mg of norethisterone (NE) in the luteal phase of the previous cycle. The objectives of the study were to determine the effect of a synthetic progestin, given for 5 to 14 days beginning on day 21 of the cycle before the IVF cycle, on folliculogenesis, estrogen secretion, the luteinizing hormone (LH) surge, luteal function, and IVF success. It was found that this treatment was easy to administer and well tolerated by patients. At the 10-mg dose, patients uniformly had vaginal bleeding 2 to 4 days after NE, whereas 40% of patients using the 2.5-mg dose bled before NE was discontinued. Significantly lower estrone glucuronide excretion in the early follicular phase and lower luteal phase pregnanediol excretion in patients receiving 10 mg NE suggested a delay or reduction of developing follicles after luteal phase suppression. No spontaneous LH surges were found in the 10-mg group, compared with surges in 5 of the 13 cycles of the 2.5-mg group. There were no differences between regimens in cycle or luteal phase length. It is postulated that NE, by suppressing folliculogenesis in the luteal phase, may provide for a smaller, but more homogenous cohort of follicles available for exogenous stimulation and recovery.

Creatinine↗
PubMed1988

Inhibin.

Inhibin is a glycoprotein which specifically inhibits FSH secretion. In follicular fluid, several forms of inhibin have been identified with mol. wts between 120 and 32 kd. The smallest active form is a glycosylated 32-kd protein with an 18-kd A chain and a 13-kd B chain. The secretion of inhibin by granulosa cells of the follicle is stimulated by FSH and testosterone, but not LH, and treatment of women with clomiphene and HMG/FSH results in an increase in the plasma concentration of inhibin. However, during the follicular phase of the normal menstrual cycle, FSH is inhibited mainly by oestradiol and inhibin levels remain constant or decline in parallel with those of FSH. It is probable that inhibin and oestradiol act together to cause the suppression of FSH. During the luteal phase, the human corpus luteum under the influence of LH secretes inhibin as well as oestradiol and progesterone. This combined negative feedback signal from the corpus luteum accounts for the suppression of FSH release and thus the failure of follicular growth during the luteal phase.

Animals↗
PubMed1988

Sexing whole human pre-embryos by in-situ hybridization with a Y-chromosome specific DNA probe.

We have used DNA-DNA in-situ hybridization with a DNA probe for the human Y-chromosome to distinguish between male and female human pre-embryos. Both biotinylated and tritiated Y-probes worked well on control cell cultures where 100 interphase nuclei were scored. Morphologically normal pre-embryos could be sexed with confidence with the tritiated Y-probe but the biotin results were less reliable (although only a few pre-embryos were analysed in this way). Early cleavage stage pre-embryos had large nuclei with relatively diffuse Y-bodies and were more difficult to score with the biotinylated Y-probe. Morphologically abnormal pre-embryos often had large nuclei with multiple Y-bodies (presumably polyploid nuclei) or small nuclei with no Y-bodies (possibly fragmenting nuclei). In all, 38 cleaving and two non-cleaving pre-embryos were analysed. The incidence of false positive and false negative cells seen after hybridization of tritiated Y-probes to control lymphocyte cultures suggests that it should normally be possible to distinguish morphologically normal male and female pre-embryos with samples of three to six interphase nuclei.

Blastocyst↗
PubMed1988

Effects of preovulatory tamoxifen in regularly cycling women on folliculogenesis, oocyte recovery and luteal function.

Forty women undergoing elective sterilization and oocyte donation were randomized in a trial to study the effects of administration of 30 mg of tamoxifen 12 h before injection of human chorionic gonadotrophin and 48 h before oocyte capture. Cycles were regulated for advanced operative scheduling with norethisterone given in the luteal phase of the previous cycle and 150 mg of clomiphene given in the early follicular phase of the recovery cycle. Tamoxifen cycles showed a delay of peak urinary oestrone excretion by 2 days, associated with a slight decrease in total excretion. Tamoxifen administration lengthened treatment cycles by 0.5 days and the luteal phase by 0.4 days. The urinary excretion peak of pregnanediol was 3 days later than in controls. Total pregnanediol excretion was slightly elevated. There were no differences in oocyte recovery rate although cleavage rate was decreased (0.84 versus 0.65, not significant at P greater than or equal to 0.05). Intrafollicular oestradiol levels were similar (794 +/- 97 versus 735 +/- 102 ng/ml). Intrafollicular progesterone levels were marginally lower in tamoxifen cycles (3.5 +/- 0.5 versus 2.3 +/- 0.8 micrograms/ml).

Adult↗
PubMed1988

The binding of epidermal growth factor to the human uterus and leiomyomata in women rendered hypo-oestrogenic by continuous administration of an LHRH agonist.

The binding of epidermal growth factor (EGF) to human myometrium and leiomyomata was assessed in a group of women rendered hypo-oestrogenic with the LHRH agonist Zoladex (ICI 118630). The results were compared with those obtained with tissues from women with normal cycles. In normal women, the specific binding of radiolabelled [125I] EGF to both myometrial and fibroid homogenates did not vary during the menstrual cycle, but the specific binding of [125I] EGF to fibroid in women treated with LHRH agonist was significantly less than in the untreated group. Since the hypo-oestrogenic state induced by the agonist is associated with a decrease in fibroid size, the results suggest that the effect of oestrogen on fibroid tissue may partly be mediated by EGF.

Adult↗
PubMed1988

Early pregnancy termination: a comparison between vacuum aspiration and medical abortion using prostaglandin (16,16 dimethyl-trans-delta 2-PGE1 methyl ester) or the antiprogestogen RU 486.

Three different regimens for termination of early pregnancy by medical means were compared to vacuum aspiration. Women seeking therapeutic abortion of pregnancy (less than or equal to 56 days amenorrhoea) were allocated to one of four treatment groups: (1) vacuum aspiration (n = 28); (2) 1 mg vaginal pessary of a prostaglandin analogue (gemeprost) every 3 h for up to 5 pessaries (n = 30); (3) the antigestogen (RU 486--mefipristone) 150 mg per day for 4 days by mouth (n = 20); (4) RU 486 in the same dose as group 3 together with 1 mg gemeprost on day 3 (n = 19). Complete abortion occurred more often in women treated with vacuum aspiration (96%), gemeprost alone (97%) and RU 486 plus gemeprost (95%) than in those treated with RU 486 alone (60%). In women receiving up to five gemeprost pessaries alone vomiting occurred in 7 (23%) and diarrhoea in 10 (33%); 16 (53%) required parenteral opiates for relief of pain. Side-effects and analgesic requirements were much reduced in the women who received RU 486 alone or in combination with a single gemeprost pessary. There was no difference in the number of days of vaginal bleeding after abortion between the four groups although there was wide individual variation (mean 10 days, range 1-34). These results confirm that medical induction of abortion in early pregnancy with prostaglandin vaginal pessaries is as effective as vacuum aspiration and that the dose can be reduced five-fold without loss of efficacy when used in combination with RU 486.

Abortion, Therapeutic↗
PubMed1988

Gonadotropic stimulation of inhibin secretion by the human ovary during the follicular and early luteal phase of the cycle.

We studied the pattern of secretion of inhibin bioactivity from the ovary into peripheral blood during the follicular and early luteal phase of the menstrual cycle in women receiving gonadotropin therapy. Multiple follicular development was stimulated in 5 women undergoing in vitro fertilization and embryo transfer for tubal infertility using three different treatments designed to vary the concentration of FSH and LH (14 cycles). The women received clomiphene citrate (150 mg/day) from days 2-6 alone or supplemented with either exogenous human menopausal gonadotropin (28 IU/3 h) or pure FSH (28 IU/3 h) from day 6 until the day of follicle aspiration. Inhibin concentrations increased 10-fold in parallel with those of estradiol, from 0.2-0.3 U/mL on day 2 (before the onset of treatment) to 4-5 U/mL on day 14 of the cycle (time of the peak LH level). Coincidental to the LH surge, the inhibin concentration declined 2- to 3-fold before increasing again early in the luteal phase. The concentration of inhibin was higher in the gonadotropin-treated group (clomiphene plus human menopausal gonadotropin/FSH) than in the group treated with only clomiphene during the follicular phase. The number of follicles stimulated was significantly higher (P less than 0.001) in the group given exogenous gonadotropins [4.8 +/- 0.4 (SE)] than in the clomiphene alone group (2.2 +/- 0.4). These data strongly suggest that both the Graafian follicles and the corpus luteum secrete inhibin, which together with estradiol and progesterone may play a role in the regulation of FSH secretion during the luteal phase.

Adult↗
PubMed1988

Comparison of inhibin immunological and in vitro biological activities in human serum.

A comparison of serum inhibin levels in men and women was undertaken using a sensitive sheep pituitary cell in vitro bioassay and a newly developed heterologous RIA. The RIA was based on an antiserum raised to bovine 31K inhibin using [125I]31K inhibin as tracer. Bovine inhibin alpha- and beta-subunits, bovine activin-A, transforming growth factor-beta, and Mullerian inhibitory substance did not cross-react in the RIA. In both assays, dilutions of serum gave response lines parallel to that of the partially purified human follicular fluid inhibin preparation used as standard. Negligible levels of both bio (B)- and immuno (I) activities were found in serum from women with premature ovarian failure or castrated men. In ovulation-induced cycles, serum B inhibin levels increased progressively from the early to the late follicular phase and remained at the late follicular phase level during the early and midluteal phases. Serum I inhibin levels also rose during the follicular phase, but declined during the early luteal phase before increasing again in the midluteal phase. As a consequence, inhibin B:I ratios varied during the treatment cycle, with high ratios in early follicular (2.86) and early luteal (2.25) phases and a low ratio in the midluteal phase (1.09). Similar changes in serum B:I ratios also occurred during the midcycle and midluteal phases of normal cycles. The B:I ratio was lower (0.35) in normal men. We conclude that the largely similar pattern of inhibin biological and immunological activities in serum obtained during a variety of physiological conditions support the validity of the RIA procedure, and the B:I ratio of serum inhibin varies during the follicular and luteal phases of the cycle and is low in men. Potential reasons for these changes in B:I ratio include the presence of interfering substances in either the bioassay or the RIA, the presence of inhibin isoforms, and/or modulation of secreted forms by sex steroids.

Adult↗
PubMed1988

The return to ovulation following early abortion: a comparison between vacuum aspiration and prostaglandin.

The return to ovulation following early abortion (less than or equal to 56 days amenorrhea) has been assessed after both vacuum aspiration under general anesthesia (N = 14) and menstrual induction with 16,16 dimethyltrans-delta 2PGE1 methyl ester in pessary form (N = 18). The urinary excretion of hCG, total estrogen and pregnanediol was similar in each group. There was an initial rapid decline in hCG excretion (t1/2 48 h), reaching 10% of the pre-treatment value after 6 days. Twenty-nine (91%) women showed a luteal phase rise in pregnanediol excretion, with ovulation occurring on day 29 (16-37) and 24 (16-32) in the vacuum aspiration and prostaglandin groups, respectively (median (range) NS). The wide range in the return of ovarian activity was related to the variation in decline of progesterone secretion (as reflected by excretion of pregnanediol) by the corpus luteum. Asynchrony between the ovarian and menstrual cycles resulting from a delay to ovulation presents a major constraint to the use of early pregnancy interruption as a routine method of fertility control.

Abortion, Induced↗
PubMed1988

The sheep corpus luteum secretes inhibin.

An experiment was performed in 20 Merino ewes in which ovarian venous blood was collected by venepuncture at surgery and at two stages of the oestrous cycle. The ovarian venous concentrations of inhibin, oestradiol-17 beta and progesterone were determined. The results demonstrate that during the luteal phase of the oestrous cycle the ovarian venous blood draining an ovary containing luteal tissue contains significantly more inhibin bioactivity than ovarian venous blood from an ovary not containing luteal tissue. During the follicular phase the concentration of inhibin bioactivity in ovarian venous blood was reduced compared with the luteal phase. From this data we conclude that the sheep corpus luteum secretes inhibin bioactivity into the ovarian venous blood.

Animals↗
PubMed1988

Inhibin secretion by the sheep ovary during the luteal and follicular phases of the oestrous cycle and following stimulation with FSH.

The secretion of oestradiol and inhibin were measured during the follicular and luteal phase of the cycle by a sensitive bioassay using sheep pituitary cells in culture in four ewes in which the left ovary had been autotransplanted to the neck. On day 12 of the cycle, premature luteal regression was induced with an injection of 100 micrograms cloprostenol (prostaglandin F2 alpha analogue; PG) and ovarian venous blood was collected every 4 h for 72 h. These same four ewes were infused in the ensuing cycle with NIH-oFSH-S14 at 10 micrograms/h for 48 h immediately after an injection of PG and sampled as above. During the luteal phase (-2 h before PG) both in the control and FSH-infused cycles the inhibin secretion rate (SR) was 27-45 units/min. After PG injection, the inhibin SR declined with time to reach 3.6-5 units/min at the onset of the LH surge (60 h after PG) in the control cycle. In contrast, in the following cycle infusion of FSH after PG injection caused a slight increase in the inhibin SR which then remained raised at 42-50 units/min for up to 60 h after PG. In the late follicular phase the oestradiol SR was greater in the FSH-infused than in the control cycles, indicating multiple follicular development. In the FSH-infused cycle the preovulatory surges of LH and FSH were markedly attenuated. These data demonstrate that (1) inhibin SR is high during the luteal phase suggesting that the sheep corpus luteum secretes inhibin, (2) in the control cycle inhibin SR declines during follicular maturation at a time when oestradiol SR is increasing but FSH levels are decreasing, and (3) exogenously administered FSH stimulates the secretion of inhibin from the ovary during the follicular phase.

Animals↗
PubMed1988

Secretion of bioactive inhibin by the ovary of the Booroola Merino ewe with or without a copy of the fecundity (F) gene.

The secretion rates of bioactive inhibin, oestradiol and progesterone were measured during the mid-luteal phase and at various times during the follicular phase of the cycle by a sensitive bioassay using sheep pituitary cells in culture in 12 Booroola ewes with and without copies of the Fecundity (F) gene in which the left ovary had been auto-transplanted to the neck. Inhibin secretion was high during the luteal phase and fell in the early follicular phase in all genotypes (P less than 0.01). In Booroola ewes with a F/- genotype, inhibin secretion then increased again, towards luteal rates, in the mid and late follicular phases. In Booroola ewes without a copy of the F gene (+/+) inhibin secretion remained low at all three sampling times in the follicular phase. The secretion rate of inhibin at 36 h (P less than 0.1) and 48 h (P less than 0.01) were significantly lower in ewes from the +/+ (no copy of the gene) ewes than in F/- (one copy of the gene) ewes. Oestradiol secretion was low during the luteal phase and increased steadily during the early (24 h) to a plateau in the mid (36 h; P less than 0.01) and late (48 h; P less than 0.05) follicular phase. Progesterone secretion was high during the luteal phase, and decreased to a very low rate by 24 h after prostaglandin (PG) treatment (P less than 0.001) and remained low. At 24 h after PG the concentration of FSH was significantly lower (P less than 0.01) than that during the luteal phase and remained suppressed until the onset of the LH surge.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Prostaglandins and antigestagens for the interruption of early pregnancy.

During pregnancy the uterus is maintained in a quiescent state by the secretion of progesterone. Antigestagens antagonize the biological action of progesterone by binding to the nuclear receptor in the target organs. Administration of the antigestagen mifepristone to women induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. In addition, the sensitivity of the myometrium to exogenous prostaglandins is markedly increased. Although mifepristone will induce bleeding in the majority of women in early pregnancy, the incidence of incomplete abortion or ongoing pregnancies increases with increasing gestational age and is too high to be clinically useful as an agent for therapeutic abortion. However, a single dose of mifepristone (400-600 mg) followed by a vaginal pessary of a prostaglandin analogue (0.5-1.0 mg), gemeprost, induced complete abortion in 95 of 100 women of gestational age less than 42 days (less than or equal to 56 days amenorrhoea). The incidence of diarrhoea (15%) and abdominal pain requiring opiate analgesia (10%) was much lower than when abortion was induced with prostaglandin alone. Vaginal bleeding continued for 13.8 +/- 0.8 days after administration of the prostaglandin. A combination of an antigestagen with a small dose of a prostaglandin analogue is an effective alternative to vacuum aspiration for the therapeutic termination of early pregnancy.

Abortifacient Agents↗
PubMed1988

Chromosome anomalies in early human embryos.

A study of the chromosome constitution of an unselected group of human preimplantation embryos fertilized in vitro showed that, of 30 studied, 7 (23%) were abnormal: 6 were aneuploid, half being trisomic and half monosomic. If the increased maternal age of the oocyte donors and the lethality of autosomal monosomy is taken into account, the frequency of this kind of error is of the same order as in clinically recognized pregnancies. One oocyte had a structural abnormality. The cause of this kind of error is unknown but could be due to errors arising in spermatozoa or oocytes or the effect of environmental factors. A 'reject' group of oocytes with 3 pronuclei showed heterogeneity with respect to their chromosome complements, only one being triploid. The frequency of tripronucleate oocytes after in-vitro fertilization appears to be higher than in clinically recognized pregnancies, presumably because of the influence of superovulation on the oocytes and, under our conditions, this frequency is 9%. Therefore, if the selected and 'rejected' groups of embryos are considered together, 10 out of 33 (30%) embryos can be considered as abnormal.

Adult↗
PubMed1987

Induction of therapeutic abortion in early pregnancy with mifepristone in combination with prostaglandin pessary.

Therapeutic abortion was induced in 100 women in early pregnancy (less than 56 days' amenorrhoea) with a combination of the antigestagen mifepristone (RU 486) and a synthetic prostaglandin analogue, gemeprost. Mifepristone in oral doses of 400-600 mg was followed 48 h later by a gemeprost vaginal pessary (0.5-1.0 mg). Bleeding was induced in all women 22-70 h after the mifepristone dose and although bleeding continued for 4-43 days (median 12) the total measured blood-loss was only a median of 72.5 ml (range 15-398). Complete abortion occurred in 95 women. Surgical evacuation of the uterus for minimum debris was required in the remaining 5. Only 10 women had diarrhoea or pain that required opioid analgesia. The combination of mifepristone and gemeprost provides a safe and effective alternative to surgical evacuation of the uterus for therapeutic abortion in early pregnancy.

Abortifacient Agents↗
PubMed1987

Sexing the human pre-embryo by DNA-DNA in-situ hybridisation.

Human male pre-embryos were identified by means of DNA-DNA in-situ hybridisation with a commercially available DNA probe for Y-chromosome DNA. This method could lead to prenatal diagnosis of genetic disorders based on small numbers of cells that are not necessarily in division, such as cells obtained from a pre-embryo during the course of in-vitro fertilisation therapy.

Autoradiography↗