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Biomedical subjects

R Homburg

Publications and source records attributed to R Homburg.

At least 55 records · Page 3Linked to original sources
PubMed1993

In vitro fertilization and embryo transfer for the treatment of infertility associated with polycystic ovary syndrome.

OBJECTIVE: To examine the outcome of treatment with IVF-ET of women with polycystic ovarian syndrome (PCOS) who failed to conceive on conventional treatment. DESIGN: Retrospective analysis with an age-matched control group. SETTING: University hospital infertility clinic and IVF unit. PATIENTS. INTERVENTIONS: Sixty-eight women with PCOS who had failed to conceive on treatment with clomiphene citrate and during six ovulatory cycles on gonadotropins underwent 208 cycles of IVF-ET. An age-matched group of 68 women with a tubal mechanical factor who received 143 treatment cycles during the same period served as controls. MAIN OUTCOME MEASURES: Cumulative conception rates, the cumulative livebirth rates, and IVF-ET data were compared between the two groups. Results of treatment with and without GnRH agonist (GnRH-a) within the groups were also compared. RESULTS: A comparison of PCOS and mechanical factor (control) groups showed almost identical results at 6 months for cumulative conception rate (82% versus 85%) and cumulative livebirth rate (69% versus 65%). Significantly more oocytes were retrieved but a smaller percentage fertilized in PCOS, and the pregnancy rate per ET did not differ between the two groups (23% versus 26%). Treatment with GnRH-a and gonadotropins as opposed to gonadotropins alone improved the cumulative conception rate, miscarriage rate, and cumulative livebirth rate in the PCOS but not in the control group and improved fertilization rates in both groups. CONCLUSIONS: For patients with PCOS who fail to conceive with gonadotropin treatment, IVF-ET is a successful treatment alternative, producing results equal to those for women with a mechanical tubal factor. Better results were achieved with GnRH-a in women with PCOS but made no difference to those with a mechanical tubal factor compared with treatment with gonadotropins alone.

Adult↗
PubMed1993

Ovulation induction in gonadotrophin-resistant women.

The patient who has gonadotrophin-resistant ovaries and who requires ovulation induction or superovulation for IVF presents a serious problem. The diagnosis is usually made in the first treatment cycle which is either abandoned due to a failure of response, requires inordinately high doses of gonadotrophins to induce a response or fails to induce satisfactory oestradiol levels and/or follicular development. This situation is often associated with advanced maternal age and high day 3 concentrations of FSH. The possible treatment strategies that we have described seem to offer only a partial solution to specific subgroups of poor responders. These include protocols of clomiphene/hMG, mini-dose GnRH agonist regimens, and cotreatment with GH, each of which may be found to be effective in individual cases. Taking into account today's increasing demand for pregnancy in older aged women, more research is needed to evolve more efficient solutions for this difficult problem.

Anovulation↗
PubMed1993

Induced regeneration of endometrium following curettage for abortion: a comparative study.

A significant increase in endometrial thickness and volume was observed in 30 patients given oestrogen and progestin supplementation following curettage for first trimester abortions, compared with 30 women who received no treatment. This indicates an enhanced regeneration of the endometrium following treatment. The ability to induce this response, creating a space between the intra-cavity surface area a short time after abortion, may theoretically be suggested as preventative treatment to reduce the risk of intrauterine adhesions.

Abortion, Induced↗
PubMed1993

The choice of treatment for anovulation associated with polycystic ovary syndrome following failure to conceive with clomiphene.

The choice of treatment for clomiphene-resistant anovulation associated with polycystic ovary syndrome (PCOS) is presently arbitrary and selection criteria are not available. A total of 144 women with anovulatory infertility associated with PCOS who failed to conceive on clomiphene were treated with either pure follicle stimulating hormone (FSH) (n = 29), or human menopausal gonadotrophin (HMG) (n = 60), or gonadotrophin-releasing hormone analogue (GnRHa) and HMG (n = 55). Analysis of 306 treatment cycles and 53 pregnancies revealed a cumulative conception rate at 4 months of 23% with FSH, 47% with HMG and 69% with GnRHa + HMG. The miscarriage rate was highest in the HMG group (44%) and consequently the cumulative live birth rate was superior when GnRHa was used in combination with HMG. There were no significant differences in the basal clinical and endocrinological features of those who conceived compared with those who did not, either in the whole group, or in the individual treatment groups. Thus, the choice of treatment for clomiphene-resistant women with PCOS cannot be guided by the basal clinical or endocrinological features of this heterogeneous syndrome with the present state or knowledge.

Adult↗
PubMed1992

The role of treatment with growth hormone in infertile patients.

The reality of the interaction of GH and its mediator, IGF-I, with gonadotrophins is now established. The results of these studies and others have obvious implications, both physiologically and clinically. Co-treatment with GH augments the gonadal response to gonadotrophins, and it seems to be of particular value in patients who are poor responders to gonadotrophin treatment and who have pituitary hypofunction induced surgically, idiopathically (hypogonadotrophic hypogonadism) or medically (treatment with GnRH analogues). There is conflicting evidence as to whether the observed effect of GH is exerted directly on the ovary or mediated through IGF-I. Treatment with GH causes a distinct increase in serum IGF-I concentrations, which correlate with, but are always higher than, follicular fluid levels, suggesting that GH stimulates hepatic production of IGF-I and that the effect on the ovary is endocrine. Further research will, hopefully, clearly define the precise therapeutic role of GH in the induction of ovulation, the selection of the most appropriate group of patients to be treated, and the minimum dose of GH needed to sensitize the ovary. Further studies are also needed to explore the action of GH and to define the role of IGF-I in the process of follicular development.

Adult↗
PubMed1992

The role of insulin-like growth factor-1 (IGF-1) and IGF binding protein-1 (IGFBP-1) in the pathogenesis of polycystic ovary syndrome.

The objective of this study was to elucidate the relationship and role of insulin-like growth factor-1 (IGF-1), IGF binding protein-1 (IGFBP-1), insulin and luteinizing hormone (LH) in the pathogenesis of polycystic ovary syndrome (PCOS). In a pilot study, serum concentrations of IGF-1 were determined in women with PCOS (n = 10), hypopituitarism (n = 12) and normal controls (n = 10). In the main study, serum concentrations of IGF-1, IGFBP-1, insulin and LH in women with anovulation associated (n = 23) and not associated (n = 47) with PCOS were determined. Serum concentrations of IGF-1 were not different in women with PCOS, anovulatory non-PCOS and healthy women but were low in those with hypopituitarism. Mean serum IGFBP-1 in PCOS (33.8 +/- 21.2 micrograms/l) was decreased compared with anovulatory non-PCOS (60.0 +/- 22 micrograms/l) (P = 0.0001), and correlated negatively with insulin concentrations (r = -0.67, P = 0.0006). Patients with PCOS could be separated into those with high LH and those with high insulin levels. It was concluded that women with PCOS have normal serum IGF-1 concentrations but IGFBP-1 levels, regulated by insulin, are low. Hyperinsulinaemia and raised LH are independently capable of stimulating ovarian androgen production. Growth factors may have an important role in the pathogenesis of PCOS.

Adult↗
PubMed1991

CV 205-502--effectiveness, tolerability, and safety over 24-month study.

Twenty hyperprolactinemic women (median prolactin [PRL] 2,989 mU/L, range 1,149 to 11,910 mU/L), previously unsuccessfully treated with bromocriptine, were treated in a prospective study, for 3 to 24 months with the new, nonergot, long-acting, dopamine agonist, CV 205-502. Treatment resulted in normalization of PRL in 14 patients, in one daily dose of 0.075 to 0.150 mg of the drug. Three patients were treated in doses above 0.150 mg up to 0.300 mg, but PRL was not normalized during the study. Menstrual function was restored in 15 of 18 amenorrheic patients. Galactorrhea, present in 7 patients, disappeared in 5. Four patients became pregnant and gave birth to healthy children. In conclusion, we found CV 205-502 effective in one daily dose, with good tolerability; it is safe and provides a valuable alternative to the dopamine agonist drugs in use today.

Adult↗
PubMed1991

The pathogenesis of the ovarian hyperstimulation syndrome (OHS): a possible role for ovarian renin.

Two patients with severe ovarian hyperstimulation syndrome are described. Increased plasma concentrations of immunoradiometrically determined total renin are shown, together with greatly increased plasma levels of active renin and aldosterone. These very high values for total renin, renin activity and aldosterone were not suppressed when extracellular compartments were greatly expanded; the values subsequently declined to normal levels, despite the use of diuretics. This suggested that the renin was of non-renal origin since its production was apparently unaffected by influences which control juxtaglomerular secretion. The high concentrations of the renin-angiotensin-aldosterone system suggest that it contributes to the genesis of the ovarian hyperstimulation syndrome.

Adult↗
PubMed1991

Combined growth hormone and gonadotropin treatment for ovulation induction in patients with non-responsive ovaries.

Four anovulatory patients who did not respond to large doses of hMG over 18-33 days were co-treated in subsequent cycles with human growth hormone. Treatment with growth hormone markedly raised serum insulin-like growth factor concentrations. Two patients had a dramatic ovarian response within 7 days of co-treatment; two menopausal patients did not respond. This combined therapy may be of practical value for ovulation induction in non-menopausal patients with non-responsive ovaries.

Addison Disease↗
PubMed1990

Cotreatment with human growth hormone and gonadotropins for induction of ovulation: a controlled clinical trial.

A randomized, double-blind, placebo-controlled trial of cotreatment with biosynthetic, human sequence, growth hormone (GH), and human menopausal gonadotropins (hMG) for induction of ovulation was performed in 16 women with amenorrhea and anovulatory infertility. Patients were randomly allocated to treatment with hMG + GH (24 IU on alternate days, total dose 144 IU) or hMG + placebo. Those who received placebo were given GH in a subsequent course of treatment. On cotreatment with GH compared with placebo, there was a significant reduction in the required dose of hMG, duration of treatment, and the daily effective dose of gonadotropins. Serum insulin-like growth factor-I (IGF-I) rose during treatment with GH but not with placebo. We conclude that growth hormone augments the response of the human ovary to stimulation by gonadotropins. These results suggest a role for the use of GH in induction of ovulation.

Adult↗
PubMed1990

Treatment with pulsatile luteinizing hormone-releasing hormone modulates folliculogenesis in response to ovarian stimulation with exogenous gonadotropins in patients with polycystic ovaries.

Combined treatment with pulsatile LH-RH and hMG, given to eight patients who had anovulation associated with PCO and resistant to CC, significantly reduced the number of large follicles induced by hMG alone. A direct effect of pulsatile LH-RH on the ovary is postulated. This combined treatment eased the problems of multifollicular development, thereby increasing efficiency and reducing complications in patients with PCO stimulated by gonadotropins.

Female↗
PubMed1990

Induction of ovulation with pulsatile GnRH.

The use of pulsatile GnRH to treat infertile women who do not ovulate has been shown to be safe, simple, and effective and the preferred method of inducing ovulation in appropriately selected patients who are resistant to treatment with clomiphene citrate. Treatment with GnRH is particularly effective for restoring ovulation in patients with idiopathic hypogonadotrophic hypogonadism and partially recovered weight-related amenorrhoea, but less successful in patients with polycystic ovary syndrome and organic hypothalamic pituitary disease. Based on personal experience, we advocate routine use of the subcutaneous route, using 15 micrograms per pulse every 90 min, and we monitor the patient's progress by serial ultrasound scanning and measurement of serum gonadotrophin and oestradiol concentrations. If the patient does not respond we recommend adding treatment with clomiphene citrate (Homburg et al, 1988b). Treatment with intravenous GnRH is reserved for women who do not respond to the above combination of drugs. We do not treat patients with GnRH until their body mass index is in the normal range (between 20-25) and we avoid GnRH treatment in patients with hypersecretion of LH during the follicular phase. If LH concentrations are raised, an alternative method of treatment is recommended, such as ovarian diathermy (Armar et al, 1990). Finally, the question of whether GnRH deficiency in patients with hypogonadotrophic hypogonadism is caused by a specific genetic lesion is not yet fully resolved. Yang-Feng et al (1986) used a cDNA clone encoding the human GnRH precursor molecule in order to assign the GnRH gene to a particular human chromosome. They found a single site for GnRH sequences in the human genome and that the gene coding for GnRH is located on the short arm of chromosome 8. Experiments in the congenitally hypogonadal mouse have shown that it is possible to restore gonadal development and gametogenesis by gene transfer (Mason et al, 1987). Clearly an abnormality at the level of the genome may be responsible for the secretory defect in patients with hypogonadotrophic hypogonadism, but it has yet to be defined (Weiss et al, 1989). Presumably elucidation awaits the development of more refined methods because both the genetics and the clinical associations of GnRH deficiency are most persuasive. Meanwhile replacement treatment with GnRH provides a simple and safe form of treatment for managing the clinical syndromes of GnRH deficiency.

Anovulation↗
PubMed1990

Combined luteinizing hormone releasing hormone analogue and exogenous gonadotrophins for the treatment of infertility associated with polycystic ovaries.

This study was designed to compare the results of treatment with, firstly, exogenous gonadotrophins, with (57 cycles) and without (65 cycles) pretreatment with a superactive analogue of luteinizing hormone releasing hormone (LHRH) and, secondly, pure follicle stimulating hormone (FSH) (50 cycles) with those of human menopausal gonadotrophin (HMG) (72 cycles) in 46 women with clomiphene-citrate-resistant anovulation associated with polycystic ovaries. Patients randomly allocated to the analogue group received buserelin (Suprefact, Hoechst, UK, Ltd, Hounslow, Middlesex), 800 micrograms/day by nasal insufflation and when hypogonadism was achieved, patients were again randomly allocated for ovarian stimulation with either FSH or HMG. Controls received FSH or HMG alone. Patients pretreated with the analogue had similar pregnancy and ovulation rates, needed larger doses and more days of gonadotrophin therapy and had more ovarian overstimulation than those receiving no pretreatment. The role of superactive LHRH analogues for induction of a single ovulation for in-vivo fertilization is thus uncertain. Pure FSH had no advantages over HMG, the LH content of HMG having no deleterious effect on the ovary.

Adult↗
PubMed1990

A double-blind study comparing a new non-ergot, long-acting dopamine agonist, CV 205-502, with bromocriptine in women with hyperprolactinaemia.

Twenty-two hyperprolactinaemic women were randomly allocated to two groups and treated with bromocriptine or the new, non-ergot, long-acting dopamine agonist, CV 205-502. The study was double-blind for 6 months. Four patients in the bromocriptine group, but none in the CV 205-502 group, discontinued the study because of adverse reactions. Adverse reactions in those receiving the new drug were milder and more transient than with bromocriptine. With once-daily doses of 0.075 mg CV 205-502, eight of 11 women achieved normal PRL concentrations after 8 weeks treatment (median (95% confidence limits), 352 (70-987) mU/l) compared with two of nine receiving a divided daily dose of 5 mg bromocriptine (1802 (1205-4438) mU/l) (P less than 0.002). With doses of 0.075-0.15 mg of CV 205-502, 10 of 11 women achieved normal PRL concentrations at 24 weeks compared with three of the remaining seven women on doses of 5-10 mg of bromocriptine. Regular menstrual bleeding was restored and galactorrhoea relieved in the majority of patients, with marginally greater efficacy with CV 205-502. CV 205-502 is highly effective for the long-term treatment of hyperprolactinaemia. It is better tolerated than bromocriptine, is effective in a once-daily dose, appears to be safe, and provides a valuable alternative to the dopamine agonist drugs in use today.

Adult↗
PubMed1990

A comparative study of single-dose growth hormone therapy as an adjuvant to gonadotrophin treatment for ovulation induction.

One intramuscular injection of biosynthetic human growth hormone (24 IU), administered on the first day of gonadotrophin treatment for ovulation induction, significantly augmented the ovarian response to gonadotrophic stimulation in seven patients. Compared with a protocol involving six injections of 24 IU of GH given on alternate days to the same patients, the smaller dose had an intermediate but highly significant effect in reducing the amount, duration of treatment and daily effective dose of hMG needed to induce ovulation. The difference between the effect of the one-dose and six-dose protocols was small. The action of growth hormone on the human ovary, probably mediated by insulin-like growth factor-1 (IGF-1), appears effective in enhancing the response to gonadotrophin therapy even when given in a single dose.

Amenorrhea↗
PubMed1989

One hundred pregnancies after treatment with pulsatile luteinising hormone releasing hormone to induce ovulation.

OBJECTIVE: To review treatment with pulsatile luteinising hormone releasing hormone in infertile women who do not ovulate and are resistant to clomiphene after 100 pregnancies achieved with this treatment. DESIGN: Retrospective analysis of 146 courses of treatment over 434 cycles. SETTING: Infertility clinic. PATIENTS: 118 Women whose failure to ovulate was due to idiopathic hypogonadotrophic hypogonadism (n = 39), amenorrhoea related to low weight (n = 17), organic pituitary disease (n = 15), or polycystic ovaries (n = 47). INTERVENTIONS: Dose of 15 micrograms luteinising hormone releasing hormone/pulse subcutaneously every 90 minutes given with a miniaturised pump throughout cycle monitored by ultrasound. Women with hypogonadotrophic hypogonadism had 48 courses, women with amenorrhoea related to low weight 23, women with organic pituitary disease 18, and women with polycystic ovaries 57. END POINT: Follow up of 100 pregnancies achieved in 77 women during six years after introducing treatment. MEASUREMENTS and main results--One hundred pregnancies (seven multiple, 28 miscarriages). Cumulative rates of pregnancy were 93-100% at six months in women with idiopathic hypogonadotrophic hypogonadism, amenorrhoea related to low weight, and organic pituitary disease. In women with polycystic ovaries (cumulative rate of pregnancy 74%) adverse prognostic factors were obesity, hyperandrogenism, and high luteinising hormone concentrations, which were also associated with a high rate of early pregnancy loss. CONCLUSIONS: Treatment with pulsatile luteinising hormone releasing hormone is safe, simple, and effective, and the preferred method of inducing ovulation in appropriately selected patients. Compared with exogenous gonadotrophin treatment there is little need for monitoring, no danger of hyperstimulation, and a low rate of multiple pregnancies.

Abortion, Spontaneous↗