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Biomedical subjects

D T Baird

Publications and source records attributed to D T Baird.

At least 235 records · Page 13Linked to original sources
PubMed1986

The effect of deliberate omission of Trinordiol or Microgynon on the hypothalamo-pituitary-ovarian axis.

The effect of deliberate omission of a phased formulation pill, Trinordiol (ethinyl estradiol 30 micrograms + levonorgestrel 50 micrograms: 6 tablets; ethinyl estradiol 40 micrograms + levonorgestrel 75 micrograms: 5 tablets; ethinyl estradiol 30 micrograms + levonorgestrel 125 micrograms: 10 tablets) or a low-dose, combined, oral contraceptive pill, Microgynon (ethinyl estradiol 30 micrograms + levonorgestrel 150 micrograms: 21 tablets) on the hypothalamo-pituitary-ovarian axis were studied. Thirty-six women were recruited to the study and divided equally between the two types of pill. Medication was begun on the 8th pill-free day of the cycle and continued for 7 days (Group 1), 14 days (Group 2) or 21 days (Group 3). Levels of FSH, LH, estradiol (E2) and progesterone (P) were measured in plasma on alternate days during the final week of pill therapy, and daily for the 7 days after stopping the pill. For the first 2 weeks of pill therapy, follicular activity, as judged by plasma levels of E2, was greater in women taking Trinordiol than in those taking Microgynon, but was similar in both groups by the third week of pill treatment. Five women taking Trinordiol (2 in Group 1 and 3 in Group 2) had plasma levels of E2 in excess of 500 pmol/l whilst taking the pills, and only 1 patient achieved this degree of follicular activity after stopping the tablets. One woman who had taken 7 days of Trinordiol (Group 1) showed a rise of plasma levels of P to 6.8 nmol/l, but luteinization did not occur in any of the remaining 35 women who took Trinordiol or Microgynon. These findings suggest that follicular activity is less completely suppressed by Trinordiol than Microgynon, at least in the first 2 weeks of pill therapy, but that normal ovulation is still a rare event in the week after cessation of either of these pills, even if only 7 days of medication have been taken.

Contraceptive Agents, Female↗
PubMed1986

A controlled release form of 16,16-dimethyl-trans-delta 2-PGE, methyl ester for early abortion.

The termination of early pregnancy (less than 56 days amenorrhoea) has been investigated using 16,16-dimethyl-trans-delta 2-PGE, methyl ester in a controlled release preparation. The onset of crampy abdominal pain was seen after 270 +/- 39 minutes and bleeding occurred after 603 +/- 95 minutes. Two (15%) patients required no pain relief during treatment, however 5 (38%) requested oral analgesia, and in 6 (46%) individuals the pain was severe enough to warrant parenteral opiates. The overall success rate for complete abortion was 85%. No serious adverse effects were seen, but vomiting occurred in 2 (15%) women, and diarrhoea in 3 (23%). Although the use of this prostaglandin analogue in slow release form provides an effective treatment method for early abortion using a reduced total dose of prostaglandin, the acceptability of the drug as an agent for menstrual induction continues to be limited by the occurrence of troublesome gastro-intestinal side effects.

Abdomen↗
PubMed1986

The effect of intrauterine administration of prostacyclin on the contractility of the non-pregnant uterus in vivo.

Prostacyclin was infused into the uterus of non-pregnant women either during early menstruation or in the secretory phase of the cycle. A dose of 5 micrograms/min produced little systemic effect and caused a significant decrease in uterine activity on Days 1 and 2 of the menses whereas 0.5 microgram/min did not. However, when dysmenorrhoeic pain and increased uterine activity were produced by infusion of PGF2 alpha during the secretory phase, PGI2 neither decreased the activity nor the pain. This indicates that PGI2 does not cause uterine relaxation by blocking the action of PGF2 alpha.

Adult↗
PubMed1986

The concentrations of prostaglandins in endometrium during the menstrual cycle in women with measured menstrual blood loss.

The concentrations of PGF2 alpha, PGE2 and 6-oxo-PGF1 alpha were measured in human uterine tissues during the menstrual cycle. The concentrations of all PGs in endometrium were greater than in myometrium. PGF2 alpha, which was found in the greatest concentrations, was high in the mid-secretory phase in both endometrium and myometrium. The concentration of PGE2 did not vary during the menstrual cycle in either tissue. The biosynthetic capacity of endometrium to produce both PGF2 alpha and PGE2 was significantly greater in the mid than the late secretory phase in the presence of exogenous arachidonic acid. Also, in spite of low endogenous concentrations, both endometrium and myometrium were able to produce significant amounts of 6-oxo-PGF1 alpha during a 30 minute incubation. The possible significance of this late secretory decline in the capacity of the endometrium to produce PGF2 alpha and PGE2 is discussed.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Characteristics of ovarian follicles in spontaneous and stimulated cycles in which there was an endogenous luteinizing hormone surge.

The growth of ovarian follicles was assessed with the use of ultrasound in spontaneous cycles and in cycles stimulated with clomiphene citrate (CC) alone, CC plus pulsatile human menopausal gonadotropin, and CC plus pulsatile follicle-stimulating hormone (FSH). At the time of the onset of the luteinizing hormone surge (LH), the size of the leading follicle did not differ significantly between the spontaneous and the stimulated cycles, although it was larger in the CC/FSH cycles. During the two days before the LH surge onset, the growth rate was faster in the stimulated than the spontaneous cycles. It is suggested that despite the provocation of extremely high plasma-estradiol levels and multiple follicular development, the leading follicle in stimulated cycles ovulated at a size equal to or greater than that in spontaneous cycles. The reason for the higher follicle size in the CC/FSH cycles is, as yet, unclear.

Clomiphene↗
PubMed1986

Comparison between clomiphene plus pulsatile human menopausal gonadotrophin and clomiphene plus pulsatile follicle stimulating hormone in induction of multiple follicular development in women.

Eighteen normally cycling women with tubal infertility undergoing in-vitro fertilization and embryo transfer were treated with clomiphene only (nine cycles), clomiphene plus human menopausal gonadotrophin (HMG) (18 cycles) and clomiphene plus follicle-stimulating hormone (FSH) (12 cycles). Clomiphene was given from day 2 to 6 (150 mg daily). HMG and FSH were injected s.c. in a pulsatile manner via a pump (28 IU every 3 h). Plasma FSH and oestradiol levels and the number of follicles greater than or equal to 16 mm in diameter were similar in the clomiphene/HMG and the clomiphene/FSH cycles, but significantly higher than in the clomiphene-only cycles. In contrast, luteinizing hormone and progesterone levels during the treatment did not differ significantly among the three regimens. Twelve of the 18 women were treated with clomiphene/HMG in one cycle and clomiphene/FSH in another and eight of them with clomiphene only in a third cycle (a total of 32 cycles). In the clomiphene/HMG cycle seven of these 12 women (58%) had plasma FSH levels during treatment similar to those in the clomiphene/FSH cycle and six of them (86%) had the same number of follicles in both cycles. A significant, but not very strong correlation was found between FSH treatment levels and the number of follicles greater than or equal to 16 mm when all 32 cycles were combined (r = 0.40). It is suggested that pulsatile HMG and FSH in combination with clomiphene are in general equally effective in inducing multiple follicular development in normal women. However, individual responses show great variability.

Clomiphene↗
PubMed1986

Endogenous luteinizing hormone surge in women during induction of multiple follicular development with pulsatile follicle stimulating hormone.

In this study nine consecutive normally cycling women undergoing in-vitro fertilization (IVF) were superovulated with clomiphene citrate followed by pulsatile 'pure' FSH injected s.c. via a pump (28 IU every 3 h). All women displayed an endogenous LH surge, which was markedly attenuated in most of the cases (peak value 44.5 +/- 5.9 U/l, duration 29.2 +/- 1.2 h, mean +/- SEM) as compared to spontaneous cycles. An increase in serum progesterone levels before the onset of the LH surge was seen in only one woman at a time when the LH values were low. During the LH surge serum progesterone levels increased significantly in all patients (12.7 +/- 1.90 nmol/l vs 4.74 +/- 1.57 nmol/l at the onset of the surge, mean +/- SEM, P less than 0.05) indicating follicular luteinization. Very high oestradiol levels in serum were found at the onset of the LH surge (7504 +/- 898 pmol/l, mean +/- SEM). Preovulatory oocytes were recovered from all women through a laparoscope 34-36 h after the beginning of the LH surge and embryos were replaced to them after IVF. One ongoing clinical pregnancy occurred. In contrast to results in monkeys, these results demonstrate for the first time that normally cycling women superovulated with clomiphene pulsatile 'pure' FSH will display an endogenous LH surge. Although the surge is attenuated implantation can occur.

Clomiphene↗
PubMed1986

Relationships between the characteristics of endogenous luteinizing hormone surge and the degree of ovarian hyperstimulation during superovulation induction in women.

Ovarian hyperstimulation was induced in 17 normally cycling women undergoing in-vitro fertilization (IVF) and embryo transfer with clomiphene (9 cycles), clomiphene followed by pulsatile hMG (12 cycles) or clomiphene followed by pulsatile FSH (11 cycles). Hyperstimulation was greater with the combined treatments than with clomiphene alone. In all 32 cycles an endogenous LH surge occurred. The peak values and the duration of the LH surge showed significant negative correlations with the plasma oestradiol levels, the number of the follicles and the total follicular fluid volume aspirated at laparoscopy. We suggest that during superovulation induction for IVF, the endogenous LH surge is attenuated by factors which are related to the degree of ovarian hyperstimulation.

Clomiphene↗
PubMed1986

Induction of ovarian activity by pulsatile infusion of LHRH in women with lactational amenorrhoea.

Four fully breast-feeding women at 6 weeks post partum were injected with LHRH (0.1 microgram/kg) every 94 min by pulsatile infusion pump. While follicular development occurred in all women, and evidence of luteinization was apparent in three out of four, normal ovulation and luteal function did not occur. This suggests that a simple disturbance in the pulsatile pattern of LHRH secretion may not, in itself, be enough to explain the suppression of ovarian activity during lactation.

Adult↗
PubMed1986

The stimulation of prostaglandin production by two antiprogesterone steroids in human endometrial cells.

Endometrial stromal cells and isolated endometrial glands obtained from women during days 6-26 of the ovarian cycle were cultured for 24 h in the presence of the progesterone antagonists 17 beta-hydroxy-11 beta-[4-dimethylaminophenyl]17 alpha-[1-propynyl] estra-4,9-dien-3-one (RU486) and 17 beta-hydroxy-11 beta-[4-dimethylaminophenyl] 17 alpha-[3-hydroxy-1-propenyl]estra-4,9-dien-3-one (ZK 98734). Both steroids stimulated prostaglandin F2 alpha (PGF2 alpha) production by stromal cells in a dose-dependent manner, in doses ranging from 10-1000 nM. Progesterone (100 nM) inhibited RU486 stimulation, except at the highest dose of antiprogestin. PGE2 was produced in smaller amounts than PGF2 alpha, but, when measurable, it also increased in the presence of RU486. In contrast, RU486 did not increase PG production by endometrial glands. In an experiment to determine the effect of pretreatment, stromal cells were incubated for 24 h with 1000 nM progesterone or RU486 (all with 100 nM 17 beta-estradiol) with either 30 or 6 microM arachidonic acid. These six batches of cells were incubated for a second 24 h with either progesterone or antiprogestin. Cells pretreated with the higher dose of arachidonic acid had a marked increase in PGF2 alpha production during the second 24 h only when also pretreated with progesterone. This finding suggests that progesterone allows an accumulation of PG precursor in a suitable accessible pool. Pretreatment with progesterone also allowed a greater conversion of PG to its 13,14-dihydro-15-keto metabolite. These results suggest that antiprogesterone steroids may act as menstrual regulators by: stimulating endogenous PG production within the endometrial stromal cells and inhibiting PG catabolism.

Dinoprost↗
PubMed1986

Toward removing uterine fibroids without surgery: subcutaneous infusion of a luteinizing hormone-releasing hormone agonist commencing in the luteal phase.

Intermittent sc injection of a LHRH agonist reduced uterine fibroid size in 5 women. Commencement of the LHRH agonist buserelin on day 21 of the menstrual cycle induced a marked increase in plasma LH and FSH concentrations, followed by rises in estradiol (E2) and progesterone. LH and FSH levels fell to within the normal range by 120 h after beginning buserelin, despite continuing administration of the agonist. After menstruation, marked sustained suppression of cyclical gonadotropin and steroid concentrations occurred: mean values of FSH, LH, and E2 were 4.9 +/- 0.5 (+/- SE) mIU/ml, 5.9 +/- 0.6 mIU/ml, and 47.9 +/- 10.8 pg/ml, respectively, during the 20 weeks of buserelin treatment. During treatment, E2 concentrations remained below 50 pg/ml in 98 of 116 weekly observations. Uterine fibroids shrank after 8 or 10 weeks of buserelin administration, as assessed by ultrasound or gynecological examination. Compared to their initial volume, mean uterine fibroid volume after 20 weeks of buserelin infusion decreased from 220 +/- 51 to 98 +/- 26 cm3, which was 39.4 +/- 6.9% of the pretreatment volume. We conclude that sc administration of a LHRH agonist beginning in the luteal phase markedly reduced the size of uterine leiomyomata, suppressed, but did not abolish, pituitary and ovarian function, and warrants further evaluation as an option or adjunctive therapy to uterine myomectomy or hysterectomy.

Adult↗
PubMed1986

The human corpus luteum secretes 5 alpha-pregnane-3,20-dione.

A radioimmunoassay for 5 alpha-pregnane-3,20-dione (5 alpha-DHP) in plasma is described. The concentration of 5 alpha-DHP in peripheral plasma during the follicular phase of the menstrual cycle was of the same order of magnitude as that of progesterone (P). During the luteal phase, the plasma 5 alpha-DHP was 8-fold higher than in the follicular phase and about 1/3 of the P concentration. The concentration of 5 alpha-DHP in ovarian venous plasma draining an ovary containing the corpus luteum was 22-fold higher than the concentration in plasma from the contralateral ovarian vein. These results show that the corpus luteum secretes significant amounts of 5 alpha-DHP.

5-alpha-Dihydroprogesterone↗
PubMed1986

Oocyte recovery and fertilization rates in women at various times after the administration of hCG.

Volunteer women requesting laparoscopic sterilization were subjected to a fixed schedule of ovulation induction and oocyte recovery. Follicle aspiration was carried out in four groups: those to whom hCG was not administered and 12, 24 or 36 h respectively after the administration of hCG. For each group oocytes were cultured in vitro for 42 h, 30 h, 18 h and 6 h respectively, before insemination with donor spermatozoa. Oocyte recovery rates improved with longer hCG-to-recovery intervals (36% with no hCG to 81% 36 h after hCG). Although there was a slight reduction in fertilization rates when oocytes were not exposed to hCG in the follicle, normal cleavage was noted in more than 50% of oocytes in all four groups. It therefore appears that the final maturation stages of the human oocyte are not dependent on the midcycle gonadotrophin surge, provided the oocyte is matured in vitro before insemination. However, it was also evident that the fertilization rates were reduced when oocytes were removed from less mature follicles, as reflected by high androstenedione/oestradiol ratios.

Androstenedione↗
PubMed1986

Changes in the concentration of prostaglandins in preovulatory human follicles after administration of hCG.

The concentrations of prostaglandins F-2 alpha, E, D-2 and 13,14-dihydro-15-keto PGE were measured in follicular fluid collected from women undergoing routine laparoscopy following induction of follicular development with clomiphene and hCG. Laparoscopy was performed before, or at 12, 24 or 36 h after administration of hCG. Prostaglandins were measured as the methyloxime derivative by radioimmunoassay. Peaks in PGE and PGF-2 alpha concentration occurred at 12 and 36 h with a significant nadir at 24 h, whereas PGD-2 production was very low at 36 h. The concentration of PGF-2 alpha rose significantly between 0 and 36 h and was greatest in follicles yielding oocytes, suggesting a possible role for this prostaglandin in the mechanism of follicle rupture.

Body Fluids↗
PubMed1986

Specificity of gonadotrophin-releasing hormone binding sites of the human corpus luteum: comparison with receptors of rat pituitary gland.

The effects of a number of analogues of gonadotrophin-releasing hormone (GnRH) on the binding of a radiolabelled GnRH agonist (GnRH-A; [D-Ser(But)6, des Gly10]GnRH-ethylamide) to homogenates of human corpus luteum (CL) and rat pituitary tissue were compared. Specific binding was inhibited by GnRH and GnRH-like peptides only. Both the C-terminal amide and N-terminal region of the GnRH molecule were required for binding in both tissues. However, amino acid substitutions at position 6 markedly enhanced, and at position 8 markedly reduced, binding potencies in rat pituitary tissue compared with human CL binding sites. These results indicate that GnRH-binding sites of rat pituitary and human luteal tissue have a similar degree of specificity for GnRH-like peptides, and a similar requirement for both N- and C-terminal regions of the peptide, but that differences in specificity related to the mid-chain region of GnRH exist between human luteal and rat pituitary binding sites.

Animals↗
PubMed1986

Measurement of exogenous and endogenous inhibin in sheep serum using a new and extremely sensitive bioassay for inhibin based on inhibition of ovine pituitary FSH secretion in vitro.

An extremely sensitive and reliable bioassay for inhibin based on inhibition of ovine pituitary FSH secretion in vitro was developed and used to measure exogenous and endogenous inhibin activity in the ewe. The sheep inhibin bioassay is 30- to 40-fold more sensitive than conventional rat inhibin bioassays. The minimum sensitivity of each bioassay in the measurement of inhibin activity in 1 ml of sheep serum is 220 mu. and 4080 mu. in the sheep and rat bioassays respectively. This sensitive inhibin bioassay has permitted, for the first time, the measurement of endogenous inhibin in the peripheral and ovarian vein blood of the sheep, as well as exogenously administered inhibin. The half-life of exogenously administered ovine inhibin (in follicular fluid) in the sheep was calculated as two components (18-24 and 50-60 min) from the inhibin profiles of six ewes. Inhibin contained in the ovine follicular fluid, given as a bolus i.v. injection, increased to maximum levels after 5 min and then remained increased for 10-32 min depending upon the dose administered, before exponentially decaying. The time for inhibin to exert its effect ranged from 3 to 6 h after injection and appeared to be dose-related. The bolus injection of inhibin, apart from causing suppression of FSH, evoked a large rebound increase of FSH up to 400% of preinjection levels. The development of the sheep bioassay will allow the measurement of biologically active inhibin in the peripheral circulation and ovarian vein blood of sheep with the possibility of extending this to man.

Animals↗
PubMed1986

Induction of ovulation during anoestrus in two breeds of sheep with multiple injections of LH alone or in combination with FSH.

The gonadotrophic requirements for the induction of ovulation and formation of a viable corpus luteum in two breeds of seasonally anoestrous sheep of differing fecundity was investigated. Welsh Mountain (n = 20) and Damline ewes (n = 19) were given LH or FSH either alone or in combination. Luteinizing hormone was injected i.v. at an increasing frequency for 72 h (one injection every 3 h for 24 h, one every 2 h for 24 h, and one every hour for 24 h) and FSH was injected in an identical manner for the first 36 h of treatment. Exogenous LH alone and in combination with FSH induced a preovulatory LH surge in all 19 ewes and ovulation in 18 out of 19 ewes of both breeds. However exogenous FSH alone was ineffective. The incidence of normal corpus luteum function in ewes induced to ovulate was low and not related to treatment, timing or magnitude of the LH/FSH surge. It is concluded that in both breeds studied it is the infrequency of LH pulses which limits the development of preovulatory follicles during seasonal anoestrus, that the requirement for FSH remains unknown, and that the induction of inadequate corpora lutea during seasonal anoestrus reflects either defects in hormonal priming of the preovulatory follicle and/or inappropriate luteotrophic support after ovulation.

Anestrus↗