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Biomedical subjects

D T Baird

Publications and source records attributed to D T Baird.

At least 37 records · Page 2Linked to original sources
PubMed2002

Measurement of inhibin A and follicular status predict the response of ewes to superovulatory FSH treatments.

Variability in superovulatory response to FSH stimulation is common to most mammals and imposes practical problems for assisted reproduction. In sheep, we have studied if this response is related to the ovarian follicular population and activity before the stimulation. During the breeding season, 30 ewes were treated with 40 mg FGA sponges for 14 days and 125 microg cloprostenol injection on Day 12, considering Day 0 as the day of progestagen insertion. Superovulatory response was induced with two different FSH regimes using the same total dose (8.8 mg), administered twice daily from 60 h before to 24 h after progestagen withdrawal. At the first FSH injection, all follicles > or = 2 mm were observed by transrectal ultrasonography and plasma FSH and inhibin A levels were determined. The number of corpora lutea and the number of and viability of recovered embryos in response to the treatment were determined on Day 7 after sponge withdrawal. No significant differences were found between treatments. The total mean number of corpora lutea (11.5 +/- 1.2) and recovered embryos (7.9 +/- 1.1) were positively correlated (P < 0.05 and <0.01, respectively) with the number of small antral follicles (2-3 mm: 9.2 +/- 0.7) and inhibin A concentration (240 +/- 18 pg/ml; P < 0.05 for corpora lutea and P < 0.005 for recovered embryos) observed at the onset of the superovulatory treatment, which was also positively correlated with the number of viable embryos (5.8 +/- 0.9, P < 0.005). In 18 ewes with follicles > or = 6 mm prior to FSH treatment, the ovulation rate was unaffected but the number of embryos (6.1 +/- 0.9 versus 11.6 +/- 2; P < 0.05) and their viability (4.5 +/- 0.8 versus 8.5 +/- 2; P < 0.05) was reduced. The lower number of embryos produced when a large follicle is present suggest that a proportion of the smaller follicles are in early stages of atresia and the developmental competence of their oocyte is compromised.

Animals↗
PubMed2002

Investigation of a novel preparation of testosterone decanoate in men: pharmacokinetics and spermatogenic suppression with etonogestrel implants.

We have investigated the pharmacokinetics and effects on the male reproductive axis of a novel preparation of testosterone decanoate (TD) with a progestogen implant. Twenty healthy Chinese men were administered TD (400 mg intramuscular 4 weekly) with two subcutaneous (SC) etonogestrel implants. Trough testosterone concentrations rose with repeated administration. Peak concentrations 1 week after the fourth injection were 31 +/- 2 nmol/liter. Both LH and FSH were rapidly suppressed and continued to fall during treatment. Spermatogenesis was also suppressed, to <or=1 x 10(6)/mL in all men with 16 (80%) azoospermic at 12 weeks. Treatment was associated with an increase in weight, and also increases in hemoglobin concentration (9%) and hematocrit (15%). No subjects withdrew from the study, although the study was terminated after subjects had completed 12 to 18 weeks as some men were found to have elevated liver enzyme tests. These data demonstrate that the pharmacokinetics of TD are improved compared to previous injectable testosterone preparations, although peak testosterone concentrations rise briefly into the supraphysiological range. The speed and degree of spermatogenic suppression suggest that this combination has promise as an effective male contraceptive.

Adult↗
PubMed2002

Patterns of follicular growth in superovulated sheep and influence on endocrine and ovarian response.

Objectives of this study were to characterize patterns of follicular development in sheep superovulated with purified follicle stimulating hormone (FSH) (OVAGEN, ICP, Auckland, New Zealand) and to determine its influence on preovulatory events (onset of the oestrus behaviour and timing of the preovulatory luteinizing hormone surge) and ovarian response (ovulation rate and embryo yield). Number and size of all >/= 23 mm follicles from the first FSH injection to withdrawal of progestagen sponges was determined by transrectal ultrasonography just prior to every FSH injection in nine Manchega ewes superovulated with eight decreasing doses (ml) (1.5 x 3, 1.25 x 2 and 1 x 3) of OVAGEN injected twice daily from 60 h before to 24 h after the withdrawal of 40 mg fluorogestone acetate sponges. Oestrous detection and jugular blood sampling for LH radioimmunoassay were performed every 3 h from 14 to 53 h after sponge removal and ovulation rate and number of embryos were determined 4 days after progestagen withdrawal. Administration of OVAGEN induced a significant rise (p < 0.0005) in the number of follicles >/= 4 mm in size because of an increased growth in size of follicles from the first FSH injection to sponge removal, an increase in the number of newly detected follicles from 12 to 36 h of the first FSH dose (p < 0.005) and a decrease in regression rate from 24 h (p < 0.001). The number of follicles 2-3 mm in size at first FSH dose (10.4 +/- 1.5) was positively correlated with the number of >/= 4 mm follicles at 0 h (19.0 +/- 2.7, p < 0.01). A higher number of >/= 4 mm follicles at 0 h was related with an earlier appearance of oestrus (31.5 +/- 1.5 h, p = 0.08) and LH surge (45.0 +/- 2.3 h, p < 0.005), and a higher ovulation rate (18.2 +/- 3.8, p < 0.005). On the other hand, the rate of embryo recovery was decreased in ewes with earlier preovulatory LH peaks (p < 0.005), with a shorter interval between oestrus and LH peak (p < 0.05).

Animals↗
PubMed2002

Investigation of hormonal male contraception in African men: suppression of spermatogenesis by oral desogestrel with depot testosterone.

BACKGROUND: Suppression of spermatogenesis to azoospermia is required for effective hormonal male contraception, but the degree of suppression varies between ethnic groups. We here report the first study of hormonal suppression of spermatogenesis in two African centres using a regimen of oral progestogen with depot testosterone. METHODS A total of 31 healthy men (21 black) were recruited in Cape Town and 21 men in Sagamu, Nigeria. Subjects were randomized to take either 150 or 300 micro g desogestrel daily p.o. with testosterone pellets. In Cape Town, desogestrel was administered for 24 weeks with 400 mg testosterone re-administered 12 weekly. In Sagamu, desogestrel was administered for 52 weeks with 200 mg testosterone (later increased to 400 mg) re-administered 12-weekly. RESULTS: In Cape Town, 22 men completed at least 20 weeks treatment. Azoospermia was achieved in 8/10 and 8/12 men in the 150 micro g and 300 micro g desogestrel groups. Four men in Sagamu withdrew. Azoospermia was achieved in all 17 men in the two groups. There were no significant changes in lipoprotein or haemoglobin concentrations in any group. CONCLUSION: These data demonstrate that the combination of oral desogestrel with depot testosterone is an effective regimen for suppression of spermatogenesis in African as in Caucasian and Chinese men, with azoospermia achieved in a total of 83/98 (85%) men.

Administration, Oral↗
PubMed2002

Oral desogestrel with testosterone pellets induces consistent suppression of spermatogenesis to azoospermia in both Caucasian and Chinese men.

BACKGROUND: Effective hormonal male contraception requires a high prevalence of spermatogenic suppression, which has proved particularly difficult in Caucasian populations. We have investigated the combination of oral desogestrel with depot testosterone in Caucasian and Chinese men. METHOD: Thirty men in Edinburgh and 36 men in Shanghai received 150 or 300 microg desogestrel p.o. daily for 24 weeks with 400 mg testosterone pellets s.c. on day 1 and at 12 weeks. RESULTS: Eight men withdrew before completing 24 weeks treatment. Testosterone concentrations remained within the normal range. Spermatogenesis was profoundly suppressed in all men. Azoospermia was achieved by a higher proportion of men in the 300 microg desogestrel group: 28/28 men versus 22/31 men (P < 0.05). All Caucasian men in the 150 microg group achieved sperm concentrations of < 1 x 10(6)/ml whereas three men in the Shanghai group maintained sperm concentrations of > 3 x 10(6)/ml. Fifteen men continued on this regimen for a subsequent 24 weeks: all remained azoospermic for the duration of treatment. High-density lipoprotein cholesterol fell by 15% in Caucasian men, but was unchanged in the Chinese men; both groups showed some weight gain. CONCLUSION: This combination of oral desogestrel with depot testosterone maintains physiological testosterone concentrations with consistent suppression of spermatogenesis to azoospermia in both Caucasian and Chinese men and therefore has many of the properties necessary for a contraceptive preparation for men.

Administration, Oral↗
PubMed2002

Male contraception.

The provision of safe, effective contraception has been revolutionized in the past 40 yr following the development of synthetic steroids and the demonstration that administration of combinations of sex steroids can be used to suppress ovulation and, subsequently, other reproductive functions. This review addresses the current standing of male contraception, long the poor relation in family planning but currently enjoying a resurgence in both scientific and political interest as it is recognized that men have a larger role to play in the regulation of fertility, whether seen in geopolitical or individual terms. Condoms and vasectomy continue to be popular at particular phases of the reproductive lifespan and in certain cultures. Although not perfect contraceptives, condoms have the additional advantage of offering protection from sexually transmitted infection. The hormonal approach may have acquired the critical mass needed to make the transition from academic research to pharmaceutical development. Greatly increased understanding of male reproductive function, partly stimulated by interest in ageing and the potential benefits of androgen replacement, is opening up other avenues for investigation taking advantage of nonhormonal regulatory pathways specific to spermatogenesis and the reproductive tract.

Condoms↗
PubMed2002

Suppression of spermatogenesis by etonogestrel implants with depot testosterone: potential for long-acting male contraception.

The coadministration of a progestogen with testosterone increases the degree of suppression of spermatogenesis and is one approach to the development of hormonal male contraception. Depot formulations may allow a reduction in dosage, minimizing adverse effects. We have investigated the effects of a sc implant containing the progestogen etonogestrel (Implanon) with depot testosterone on spermatogenesis in normal men. Twenty-eight men were randomized to receive either one or two etonogestrel implants, removed after 24 wk. All men additionally received 400 mg testosterone pellets on d 1 and at 12 wk. Four men withdrew during the study, three because of side effects. Testosterone concentrations remained within the physiological range during treatment, although they were overall slightly reduced, compared with pretreatment. Both groups showed marked suppression of spermatogenesis, nine men in each group achieving azoospermia (64% and 75% in the one- and two-implant groups, respectively). Sperm concentrations in 13/14 men in the two-implant group fell to 0.1 x 10(6)/ml or less. Spermatogenic suppression was more variable in the one-implant group, with partial recovery in three men. Incomplete suppression of spermatogenesis in the one-implant group was associated with less complete suppression of gonadotropins. There were no significant changes in body weight, hemoglobin, hematocrit, or high-density lipoprotein cholesterol concentrations during treatment. These data demonstrate that etonogestrel implants with depot testosterone provide effective suppression of spermatogenesis with reduced metabolic effects and are, therefore, a promising approach to the development of long-acting yet reversible male contraception.

Adult↗
PubMed2002

Effect of bone morphogenetic protein 2 (BMP2) on oestradiol and inhibin A production by sheep granulosa cells, and localization of BMP receptors in the ovary by immunohistochemistry.

The bone morphogenetic proteins (BMPs) have been implicated in the paracrine regulation of ovarian follicular development. In this study, we investigated the expression of the BMP receptors (BMPRs) in sheep ovaries by immunohistochemistry and the effect of BMP2, a natural ligand for these receptors, on granulosa cells cultured in vitro. Ovaries from cyclic ewes were fixed, embedded in paraffin wax and cut into sections. The sections were rehydrated, submitted to microwave antigen retrieval and treated with polyclonal antibodies against BMPR1A, BMPR1B and BMPR2. Strong immunostaining for all three receptors was observed in the granulosa cell layer of follicles from the primary to late antral stages of development. Staining was also present in the oocyte, corpus luteum, ovarian surface epithelium and, to a lesser extent, the theca layer of antral follicles. For functional studies, granulosa cells were obtained from immature follicles 1-3 mm in diameter. The cells were cultured for 6 days in serum-free medium containing 1 ng oFSH-20 ml(-1) in the presence of 0, 3, 10 or 30 ng ml(-1) human recombinant BMP2. The medium was replaced every 2 days and oestradiol and inhibin A concentrations were measured in the spent medium. In the absence of BMP2, oestradiol and inhibin A production increased as the granulosa cells differentiated in vitro. The addition of the highest dose of BMP2 enhanced oestradiol production (P < 0.05) without affecting the proliferation of the cells. It is concluded that BMP receptors are present in sheep ovaries and that BMPs may have a role in the differentiation of granulosa cells by enhancing the action of FSH.

Animals↗
PubMed2002

Production of inhibin A not B in rams: changes in plasma inhibin A during testis growth, and expression of inhibin/activin subunit mRNA and protein in adult testis.

Previous studies have shown that changes in the plasma concentrations of immunoreactive inhibin measured by radioimmunoassay occur in parallel with growth and regression of the testes during a reproductive cycle in adult Soay rams induced by exposure to an artificial lighting regimen of alternating 16 week periods of long days and short days. With the development of new two-site ELISAs for sheep inhibin A and inhibin B, we have re-examined the relationship between FSH and dimeric, biologically active inhibin in the reproductive cycle in adult Soay rams. No signal was generated by sheep testicular extract, ram or ewe plasma, or sheep ovarian follicular fluid in the inhibin B ELISA. In contrast, ram plasma contained significant activity in the inhibin A ELISA, which diluted in parallel to the inhibin A standard, and was abolished by preincubation of ram plasma with monoclonal antibodies specific for the betaA, but not the betaB, subunit. These results indicate that the ram is the first adult male mammalian species identified to date in which the testes produce and secrete dimeric inhibin A and not inhibin B. Northern blot analysis and immunocytochemistry confirmed the presence of alpha, betaA and betaB inhibin/activin subunit mRNA and protein in the testes of adult rams. Changes in plasma inhibin A concentrations occurred in parallel with the growth and regression of the testes during the long day: short day: long day lighting regimen in adult Soay rams, confirming our previous observations with immunoreactive inhibin. During the growth phase of the testes in the first 8 weeks of exposure to short days there was a positive correlation between plasma FSH and inhibin A concentrations, indicating that during this phase the secretion of inhibin A is stimulated by FSH and that inhibin A did not act as a negative feedback hormone on FSH secretion. From week 8.5 to week 16.0 of exposure to short days, there was a negative correlation between FSH and testosterone concentrations, but not inhibin, indicating that when inhibin concentrations are high, testosterone acts as the negative regulator of FSH secretion. Thus, in intact adult rams, when the testes are fully active it appears that inhibin A may sensitize the pituitary to the negative feedback effects of testosterone, at which time they act synergistically to maintain plasma concentrations of FSH.

Analysis of Variance↗
PubMed2001

The effects of peri-ovulatory administration of levonorgestrel on the menstrual cycle.

Levonorgestrel (LNG) 0.75 mg administered 12 h apart within 72 h of unprotected coitus, is an established method of emergency contraception (EC). The mechanism of action of LNG used in this manner is unknown. We administered LNG 0.75 mg twice immediately before ovulation, to test the hypothesis that LNG acts as an emergency contraceptive by abolishing the pre-ovulatory lutenizing hormone (LH) surge and thereby delaying ovulation. Twelve women took LNG on or before the day of the first significant rise in urinary LH in 12 cycles. In four women, the LH peak and the onset of next menses were significantly delayed (delay of 16.8 days (SD +/- 8.7) from the day of mean LH peak in placebo cycles). One woman did not ovulate at all, despite a normal LH peak and cycle length. In the remaining eight women, LNG did not affect ovulation or the cycle length, but the length of the luteal phase and the total luteal phase LH concentrations were significantly reduced. We suggest that LNG acts as an emergency contraceptive by other mechanisms as well as delaying the LH surge and interfering with ovulation.

Adult↗
PubMed2001

Second trimester medical abortion with mifepristone and gemeprost: a review of 956 cases.

The treatment outcomes of 956 women undergoing second trimester termination of pregnancy with mifepristone and gemeprost were studied. The median gestational age was 16 weeks (range: 12-24 weeks). All women were treated with 200 mg mifepristone orally, followed 36 h later with 1 mg vaginal gemeprost administered every 6 h to a maximum of 4 doses in the first 24 h. A second course of 1 mg vaginal gemeprost was given 3-hourly in the next 12 h, if abortion had not occurred. Overall, 96.4% and 98.8% of the women aborted within 24 and 36 h, respectively. The median induction-to-abortion interval was 7.8 h (range: 0.5-109.9 h). The induction-abortion interval was longer in nulliparous women and women with a gestation age 17 weeks or above. Surgical evacuation of the uterus was performed in 11.5% of women for incomplete abortion or retained placenta. More multiparous women (16.7%) required surgical evacuation of uterus than did nulliparous women (7.3%; p <0.001). Ten (0.1%) women failed to abort with gemeprost and required other methods for abortion. In conclusion, a combination of mifepristone and gemeprost is a safe, effective, and noninvasive method of medical abortion for second trimester pregnancy.

Abortifacient Agents, Nonsteroidal↗
PubMed2001

Noncompliance among a group of women using a novel method of contraception.

OBJECTIVE: To compare the incidence of noncompliance measured objectively by a home use fertility monitor with the traditional self-reported incidence of compliance in a study of a new method of contraception. DESIGN: Prospective cohort study. SETTING: A large family planning clinic in Edinburgh. PATIENT(S): Thirty-two healthy women who took part in a trial assessing the efficacy of a novel method of contraception involving accurately timed administration of a single dose of mifepristone. INTERVENTION(S): Mifepristone was administered orally and a blood sample was collected on the same day. MAIN OUTCOME MEASURE(S): Percentage of missed tests detected by the monitor against the self-reported percentage during the critical period. RESULT(S): Women failed to perform 24.2% (95% confidence interval, 16.5-31.5) of the tests in the 162 cycles analyzed. They missed tests at an absolutely vital time for contraceptive efficacy in 42% of cycles according to the monitor while admitting to missing tests in 14.8%. Poor compliance was associated with younger women, those who discontinued the study before completion, and cycles in which women were not relying on the contraceptive method. CONCLUSION(S): The use of microelectronic monitoring systems may improve our understanding of the extent of patient noncompliance, providing objective information that no other monitoring technique can produce. This understanding provides the opportunity to make the optimum use of potentially effective treatments while validating research evidence.

Cohort Studies↗
PubMed2001

The endocrinology of menstruation--a role for the immune system.

The human endometrium displays characteristic features, both structural and functional, across the menstrual cycle. It is the sex steroid hormones, oestrogen and progesterone, that drive the endometrium through the different phases of the cycle. Oestrogen and progesterone act sequentially to regulate cellular concentrations of their respective receptors, this interaction initiates gene transcription. Thereafter a cascade of local events prepares the endometrium for implantation, but in the absence of pregnancy, progesterone withdrawal leads to menstruation and cyclic repair. Withdrawal of progesterone from an oestrogen-progesterone primed endometrium is the initiating event for the cascade of molecular and cellular interactions that result in menstruation. Progesterone withdrawal first affects cells with progesterone receptors. Early events in the menstrual process are vasoconstriction and cytokine up-regulation. The activation of lytic mechanisms is a later event and involves cells that may lack progesterone receptors, for example, uterine leucocytes and epithelial cells. Hence progesterone withdrawal results in a local increase of inflammatory mediators and the enzymes responsible for tissue breakdown. The total complex of local factors implicated in normal menstrual and aberrant menstrual bleeding are yet to be fully defined.

Adult↗
PubMed2001

Antigestogens: the holy grail of contraception.

Progesterone is essential for the establishment and maintenance of pregnancy. The discovery of antagonists of progesterone offered the possibility of developing new methods of fertility regulation. It was very quickly demonstrated that antigestogens would induce bleeding in early pregnancy, and mifepristone in combination with a prostaglandin is used as a method of abortion in several countries. Mifepristone will also inhibit ovulation, prevent implantation and induce menstrual bleeding at the time of expected menses. However, the development of these contraceptive uses of antigestogens has been inhibited by political and ethical controversy surrounding abortion. Surely the time has come to dissociate the ongoing debate about the ethics of abortion from the method so that the full therapeutic potential of this class of drugs can be exploited fully.

Abortion, Induced↗
PubMed2001

Double-blind randomized trial of mifepristone in combination with vaginal gemeprost or misoprostol for induction of abortion up to 63 days gestation.

BACKGROUND: Gemeprost and misoprostol are two of the most widely used prostaglandins in combination with mifepristone for medical abortion in early pregnancy. However, the efficacy and side-effects of those two drugs given vaginally have not been assessed in a randomized trial. METHODS: Randomized double-blind controlled trial involving 999 women undergoing an abortion at gestational age < or =63 days who received either 0.5 mg gemeprost (group I, n = 499) or 800 microg misoprostol (group II, n = 500) vaginally approximately 48 h after taking 200 mg mifepristone by mouth. The rate of complete abortion and the side-effects were compared between the groups. RESULTS: A total of 89 cases was excluded from full analysis of outcome because either they aborted after mifepristone alone (n = 2), had an ectopic pregnancy (n = 1), or because the outcome was uncertain as they failed to attend their follow-up appointment (n = 86). The rate of complete abortion was very high (>95%) in both groups but significantly higher after treatment with misoprostol than with gemeprost [436/453 (98.7%) versus 451/457 (96.2%), P = 0.019, difference 2.5%, confidence interval 0.4-4.7%] and there were fewer ongoing pregnancies (n = 1 versus n = 8, P < 0.018). Surgical intervention rose significantly with gestation in women who received gemeprost (P < 0.03) but not with misoprostol. The incidence of side-effects such as diarrhoea (13.7 versus 16.4%) and vomiting (27.8 versus 29.7%) was similar in women who received misoprostol or gemeprost respectively, as was the duration and amount of bleeding. CONCLUSIONS: (i) Both regimens using a reduced dose of mifepristone are highly effective methods of inducing abortion in early pregnancy; (ii) vaginal misoprostol is the preferred prostaglandin because it is it is associated with fewer failures than low-dose gemeprost, particularly at gestation > or =49 days.

Abortifacient Agents, Nonsteroidal↗
PubMed2001

Feasibility of administering mifepristone as a once a month contraceptive pill.

Many women find the idea of a once-a-month contraceptive pill an attractive concept. Mifepristone has been shown to be effective as a contraceptive if administered in the early luteal phase. We tested the contraceptive efficacy of 200 mg of mifepristone on day luteinizing hormone (LH) + 2 in a group of 32 women who used a fertility monitor to identify the LH surge. We also recruited a control group, comprising 20 women who were trying to conceive. In this group, 12 women conceived during a total of 50 control cycles (probability of pregnancy 0.25-0.32). Women in the treatment group contributed to a total of 178 cycles and there were two pregnancies (probability of pregnancy 0.01). An LH surge was not detected in 34 cycles (19.1%). In 20 cycles (11.2%) this was due to imperfect use while 14 were monitor method failures (7.9%). Treatment with mifepristone in the early luteal phase did not disrupt the cycle length but women reported slight vaginal bleeding in 15% of the cycles. The combination of a home-use fertility monitor with once-a-month administration of mifepristone (especially if mifepristone is administered at the early luteal phase) is an acceptable contraceptive option with minimal side effects. Unfortunately, it is difficult to envisage how an easier way of defining the correct timing, which required less compliance, could be devised.

Adolescent↗