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Biomedical subjects

D L Healy

Publications and source records attributed to D L Healy.

At least 91 records · Page 5Linked to original sources
PubMed1991

Ovarian sensitization to gonadotrophins by human growth hormone. Persistence of the effect beyond the treated cycle.

OBJECTIVE: To document the persistence of a sensitizing effect of human growth hormone on the ovarian responsiveness to human menopausal gonadotrophin in anovulatory patients resistant to standard gonadotrophin doses. DESIGN: We performed an open study of three patients given 4, 12 or 24 IU recombinant growth hormone on alternate days for 5-7 doses, concomitantly with gonadotrophin, and assessed gonadotrophin dose requirements before, during and after the cycle of growth hormone therapy. PATIENTS: We studied two with isolated gonadotrophin deficiency and primary amenorrhoea and one with a pituitary tumour and hyperprolactinaemia which normalized with bromocriptine but in whom there was persisting secondary amenorrhoea. MEASUREMENTS: We measured body mass index, FSH, LH, prolactin, growth hormone, insulin-like growth factor I (IGF-I), oestradiol and inhibin at baseline and growth hormone, IGF-I, oestradiol and inhibin during treatment. In addition we noted the numbers of ampoules (75 IU) and the last pre-hCG dose of gonadotrophin used before, during and after growth hormone therapy. RESULTS: Baseline growth hormone levels were low but IGF-I levels were normal. IGF-I increased by 20% in the subject given 4 IU growth hormone, and by 50-100% in the other two. Pretreatment daily gonadotrophin dosage of 8-11 ampoules pre-hCG was reduced to 3-6 ampoules during growth hormone and 3-4 post growth hormone. This effect persisted for 4 cycles over 7 months in one subject. CONCLUSION: Growth hormone causes persisting ovarian sensitization to gonadotrophin and may produce a substantial lowering of gonadotrophin requirement for ovulation induction in patients with large dosage needs.

Adult↗
PubMed1991

Pelvic pain complicating LHRH analogue treatment of fibroids.

We present these 3 cases to alert others to the possibility of severe pain with rapid shrinkage of fibroids occurring during LHRH analogue treatment. We suggest management of such events should not be surgical except for vaginal excision of prolapsed fibroid polyps.

Adult↗
PubMed1990

Clinical predictors for buserelin acetate treatment of uterine fibroids: a prospective study of 40 women.

Buserelin acetate, a luteinizing hormone-releasing hormone agonist, is known to be effective in the shrinkage of uterine fibroids. A prospective trial was undertaken (1) to compare the efficacy of intranasal (IN) and subcutaneous (SC) administration of buserelin acetate and (2) to assess if tumor regression correlated with fibroid size and/or patient age. Forty patients were randomly allocated to receive 6 months of either IN buserelin acetate (n = 21) or SC buserelin acetate (n = 19). Four patients did not complete the study and were excluded from statistical analysis. Fibroid regression occurred in all 36 patients. Overall regression to 66% or less of the initial fibroid volume occurred in 70% of subjects. There was no significant difference in fibroid shrinkage between the two administration routes. A significant positive correlation was found between initial fibroid size and subsequent fibroid regression, with larger tumors being more likely to shrink than smaller fibroids. No correlation was found between the patient's age and the extent of fibroid regression.

Administration, Intranasal↗
PubMed1990

Progesterone receptor antagonists and prostaglandins in human fertility regulation: a clinical review.

Progesterone receptor antagonists have been developed by substitutions at the 11-beta and 17 side-chain positions of the progestagen norethisterone. The most studied progesterone receptor antagonists are mifepristone (Mifegyne; Roussel-UCLAF; RU486) and ZK98734 and ZK98299 (Schering AG). These compounds bind avidly to the progesterone receptor and glucocorticoid receptor but have essentially no binding to the mineralocortocoid, oestrogen or androgen receptors. Mifepristone also binds avidly to albumin, resulting in a half-life of approximately 24 h after oral administration. Progesterone receptor antagonists can induce menstruation by a direct action upon the endometrium. They have also been shown to exert weak progesterone agonist actions in certain circumstances and to modulate pituitary hormone secretion by antagonizing the feedback actions of progesterone. Moreover, they release prostaglandin F2 alpha and E2 from human endometrium or early pregnancy decidua and reduce the metabolism of these eicosanoids. Clinically, progesterone receptor antagonists have been used in trials of menstrual regulation, abortion and induction of labour, and during treatment of breast or ovarian cancer, some forms of hypertension and meningioma. Progesterone receptor antagonists have been administered to approximately 70,000 women in 18 countries as medical abortifacients. They have been proven, especially when combined with prostaglandin analogues, to be as effective as surgical methods of termination of pregnancy. Progesterone receptor antagonists have focussed international attention on menstrual regulation, abortion and the rights of women to regulate their fertility.

Abortifacient Agents, Steroidal↗
PubMed1990

Second-trimester termination with 16,16 dimethyl-PGE1-methyl ester (gemeprost), compared with a regimen that included intra-amniotic PGF2 alpha and hypertonic saline.

The use of gemeprost (16,16 dimethyl-PGE1-methyl ester) pessaries was compared in an open, randomized single-centre trial with the intra-amniotic injection of PGF2 alpha combined with hypertonic saline, intravenous oxytocin and a hygroscopic cervical dilator (Dilapan) for the termination of pregnancy between 14 and 20 weeks. There was no significant difference in the induction-delivery interval for the two groups. With the exception of an increased incidence of diarrhoea in the gemeprost group, there was no significant difference in other side effects, analgesic requirements or retained placentae. Gemeprost pessaries are an effective alternative to the more invasive methods previously used for the induction of second-trimester termination.

Abortifacient Agents, Nonsteroidal↗
PubMed1990

Relaxin in sera during the luteal phase of in-vitro fertilization cycles.

To identify the time when relaxin can first be detected in peripheral sera after in-vitro fertilization (IVF) and embryo transfer, blood samples were collected from 20 women up to 14 days after oocyte retrieval. Sixteen women did not become pregnant and in eight of them relaxin (but not beta-human chorionic gonadotrophin, beta-hCG) was measurable for the first time at days 6 to 12. Concentrations of other hormones measured were also different in these eight women compared with the remaining eight non-pregnant women; their serum concentrations of 17 alpha-OH progesterone, progesterone and oestradiol were higher but concentrations of luteinizing hormone and follicle-stimulating hormone were lower. Three women became pregnant; relaxin and beta-hCG were first detected on the same day (10 to 12). The remaining woman had increased beta-hCG levels but did not develop a clinical pregnancy. Measurement of serum relaxin during IVF cycles may allow assessment of corpora luteal function before its identification by levels of steroid hormones.

Chorionic Gonadotropin↗
PubMed1990

Inhibin and estradiol responses to ovarian hyperstimulation: effects of age and predictive value for in vitro fertilization outcome.

We have compared the time courses of serum inhibin and estradiol responses to ovarian hyperstimulation in patients undergoing in vitro fertilization and embryo transfer as well as their predictive value for outcome of intermediate variables and pregnancy in in vitro fertilization and embryo transfer. Blood samples (n = 749) were collected for up to 6 days before hCG administration in 100 consecutive treatment cycles, of which 44 resulted in pregnancy, as defined by elevated luteal phase serum hCG beta levels. Inhibin and estradiol levels increased markedly in parallel during hyperstimulation and were highly correlated (r = 0.89; P less than 0.001). Inhibin responses were significantly lower in women 35 yr of age or older (P less than 0.001), although estradiol responses were not influenced by age. Gravidity and tubal disease also had marginal effects on the time course of inhibin responses, but not on overall mean inhibin levels or estradiol responses. The time course of hormonal responses to hyperstimulation was not influenced by any other demographic or etiological factors. Peak values of both hormones correlated with the total number of follicles (inhibin, r = 0.70; estradiol, r = 0.65; P less than 0.001) and oocytes retrieved per cycle (inhibin, r = 0.49; estradiol, r = 0.39; P less than 0.001). The time course and peak values of inhibin and estradiol responses to hyperstimulation did not differ significantly between conception or nonconception cycles whether judged by biochemical (luteal hCG beta) or clinical (viable ongoing pregnancy) criteria. Luteal phase serum inhibin, estradiol, progesterone, and hCG levels were significantly higher in conception than in nonconception cycles (P less than 0.001). These data suggest that the rises in serum inhibin and estradiol levels during hyperstimulation have similar predictive properties for IVF-ET outcomes and could, therefore, be used interchangeably to monitor hyperstimulation regimens. The age-related reduction in inhibin, but not estradiol, responses suggests that these two hormones reflect different granulosa cell functions and that serum inhibin responses to maximal ovarian stimulation may be a sensitive and early index of declining ovarian function with advancing age.

Adult↗
PubMed1989

Induction of ovulation with gonadotrophin-releasing hormone--life-table analysis of 50 courses of treatment.

Ovulation induction by means of the pulsatile subcutaneous administration of gonadotrophin-releasing hormone by way of an infusion pump is described. The clinical outcome in 50 courses of treatment, which totalled 116 treatment cycles, was analysed and was compared with the pregnancy rates that were obtained with the administration of human pituitary gonadotrophins. We found that the pregnancy rates for these two treatments were similar. We also have shown that for those women who ovulated as a result of such treatment the conception rates were similar to those in ovulatory women who had discontinued contraception. We conclude that gonadotrophin-releasing hormone has an important place among the ovulation-induction agents.

Actuarial Analysis↗
PubMed1989

A controlled study of luteinizing hormone-releasing hormone agonist (buserelin) for the induction of folliculogenesis before in vitro fertilization.

Treatment with clomiphene citrate and human menopausal gonadotropin (HMG) is often used to induce folliculogenesis before in vitro fertilization, but not all women have an adequate response. It has been hypothesized that abnormally high levels of luteinizing hormone (LH) may contribute to the reduced folliculogenesis. We therefore performed a controlled, open trial in which treatment with buserelin, an agonist of luteinizing hormone-releasing hormone citrate and HMG in 44 consecutive women in whom no oocytes or only one had been produced by standard treatment with clomiphene and HMG. Twenty-nine women received buserelin with HMG, and 15 received clomiphene citrate with HMG. The median number of oocytes per patient recovered from those who received buserelin with HMG was 4 (range, 0 to 19), as compared with 0 (range, 0 to 5) in those who received clomiphene citrate with HMG. The fertilization rates of oocytes recovered from both groups of patients were similar (75.8 percent and 76.5 percent, respectively). Fifty-four percent of patients given buserelin with HMG underwent triple-embryo transfer, as compared with 13 percent of those given clomiphene citrate with HMG. Pregnancy (n = 3) occurred only among the patients receiving buserelin with HMG. In the buserelin-HMG group, significantly fewer oocytes were recovered from patients with occult ovarian failure (infertility and elevated follicular-phase levels of follicle-stimulating hormone, with regular menses) (median, 1; range, 0 to 4) than from those with other causes of infertility (median, 8; range, 0 to 19). Our data suggest that, except in women with occult ovarian failure, buserelin and HMG improve embryologic and clinical outcomes in patients with previously unsatisfactory stimulation of the ovaries for in vitro fertilization.

Administration, Intranasal↗
PubMed1989

Ovine trophoblast protein-1 and human interferon alpha reduce prostaglandin synthesis by ovine endometrial cells.

Ovine trophoblast protein-1 (oTP-1), a protein secreted by the sheep conceptus immediately prior to implantation has sequence homology with alpha interferon. We have previously shown that, in parallel with human alpha interferon (IFN), oTP-1 reduces the release of prostaglandins (PG) E and F2 alpha from cultured ovine endometrial cells. Here we have examined the time and dose dependence of these actions and the possible site of action of the peptides. The concentrations of oTP-1 and IFN required for 50% inhibition of PGE release were 92 pg/ml and 0.88 pg/ml and for PGF2 alpha release, 165 pg/ml and 1.12 pg/ml respectively. Significant effects on PG release were not measured before 12 h after addition of peptide to culture dishes. Following removal of the peptides, the cells released less PGs for a further 18 h but then recovered. A large increase in PG synthesis and release occurred from cells cultured with added serum or arachidonic acid (AA) and an interactive effect was demonstrated between them, AA having a greater stimulatory effect on PG released in the presence of serum. However, in all cases oTP-1 and IFN continued to attenuate prostaglandin release. We conclude that the IFNs act directly or indirectly on the prostaglandin synthase enzyme.

Animals↗
PubMed1989

Predicting pregnancy outcome after in vitro fertilization and embryo transfer using estradiol, progesterone, and human chorionic gonadotropin beta-subunit.

Two hundred twenty consecutive in vitro fertilization (IVF) conception cycles were studied prospectively in order to examine the predictive value of serum human chorionic gonadotropin beta-subunit (beta-hCG), estradiol (E2), and progesterone (P) in predicting pregnancy outcome between 2 and 4 weeks after oocyte collection. To examine the predictive value of each hormone in predicting clinical pregnancy outcome, each patient's result at each week was assigned a scoring system based on the 25th percentile value of the concentration of beta-hCG, E2, and P in ongoing singleton IVF pregnancies for each week of the study. All but one ectopic pregnancies had scores of 0 or 1 points between 2 and 4 weeks after oocyte collection. The scores in successful pregnancies were significantly higher than in unsuccessful pregnancies 2 weeks after oocyte collection. Ninety percent of women scoring 3 points 2 weeks after oocyte collection had ongoing IVF pregnancies. The authors conclude that determination of serum beta-hCG, E2, and P concentrations between 2 and 4 weeks after oocyte collection provides clinically useful information not only in the prediction of ectopic IVF pregnancy, but also, conversely, in the identification of IVF pregnancies that are destined to be ongoing.

Chorionic Gonadotropin↗
PubMed1989

Relaxin levels in antenatal patients following in vitro fertilization.

The aim of this study was to investigate the relationship between serum relaxin and pregnancy outcome in a group of patients pregnant after in vitro fertilization (IVF). Patients who delivered a single live infant at term after IVF had mean serum levels of relaxin more than double the mean levels in normal antenatal patients. The high relaxin levels were compatible with delivery at term. However, because of the proposed role of relaxin in the process of cervical ripening, the high serum levels may help explain the high rate of preterm labor observed among IVF patients.

Abortion, Spontaneous↗
PubMed1989

GnRH agonist administration in polycystic ovary syndrome.

The study was designed to examine (1) the effects of the luteinizing hormone releasing hormone (GnRH) agonist, buserelin, on pituitary and ovarian hormone secretion, and (2) the effect that pituitary-ovarian suppression with a GnRH agonist has on subsequent ovulation induction with exogenous gonadotrophins (hMG), in polycystic ovary syndrome (PCOS). Two protocols were studied where buserelin was administered intranasally to all patients in a dose of 200 micrograms, six times daily. Ten patients received buserelin until an oestrogen withdrawal bleed occurred while a further 12 patients received buserelin for 4 weeks, before hMG was co-administered. Nine of the above subjects also underwent conventional ovulation induction with hMG. Blood samples were taken daily for radioimmunoassay of LH (LH-RIA), FSH, sex steroids and inhibin and for immunoradiometric assay of LH (LH-IRMA). Following buserelin administration there was an initial rise in LH-RIA, FSH, oestradiol (E2) and inhibin (P less than 0.01). Fourteen days were needed for LH-RIA to return to the normal range, with both protocols resulting in a fall in LH-RIA and FSH (P less than 0.01) before hMG was co-administered. Twenty-eight days of buserelin administration were needed to suppress E2 into the castrate range. Inhibin and both E2 and FSH were closely correlated throughout buserelin administration (P less than 0.01). There was failure to respond to an intravenous bolus of 100 micrograms of GnRH from 7 days of buserelin administration onwards, despite the serum LH-RIA still being raised at 7 days. Serum samples assayed for LH by RIA using WHO Matched Reagents and by IRMA were closely correlated (r = 0.96, P less than 0.01). There was no difference in the proportion of ovulations (52% vs 66%) or pregnancies (1 vs 1) in the GnRH agonist or control group. Similar amounts of hMG were needed in both groups and there was multiple follicular development (greater than 3 follicles greater than 15 mm diameter; 41% vs 38%) following hMG administration. There was a close correlation between E2 and inhibin levels (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Intranasal↗
PubMed1989

Oocyte donation: a review.

Oocyte donation provides an option for achieving pregnancy in women lacking functioning gonads, or in whom IVF techniques have failed to harvest adequate oocytes, or those who do not wish to use their own gametes because of hereditary disease. In agonadal women, artificial menstrual cycles are required before proceeding to gamete donation. A fixed cyclical steroid replacement schedule of oestradiol (E2) valerate and progesterone (P4) pessaries was initially used, but the need for synchrony between donor and recipient cycles, and the narrow window for implantation limited the transfer of fresh embryos. Donor-recipient cycle asynchrony can be overcome by using frozen-thawed embryos, or by extending the follicular phase in the recipient to widen the transfer window. Twenty-two pregnancies have now been achieved by the Monash/Epworth group, resulting in the birth of 13 healthy infants. There were no statistically significant differences in pregnancy rates (per transfer) between transfers in natural cycles (14%, four pregnancies) and steroid replacement cycles (24%, 16 pregnancies). Five pregnancies (36%) were established in women treated with 2 mg of E2 daily 13-18 days before embryo transfer with P4 starting on the day of or the day following oocyte retrieval. E2 was continued for a median of 85 days (range 49-110) and P4 for a median of 86 days (range 49-133) after the supposed last menstrual period. All but one delivery was by caesarean section. There were no perinatal deaths and no ectopic pregnancies.

Embryo Transfer↗