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R Homburg

Publications and source records attributed to R Homburg.

At least 37 records · Page 2Linked to original sources
PubMed1997

A new concept of cotreatment with human growth hormone and menotropins in ovulation induction protocols.

Follicular development in the primordial and preantral stages is almost completely independent of gonadotrophins or steroids and is mainly dependent on growth factors and local regulators. Since human growth hormone (hGH) was found to facilitate ovarian response to gonadotrophin stimulation, we hypothesized that the administration of hGH in an hypogonadotrophic state and prior to ovarian stimulation with menotropins, may initiate or facilitate the propagation of the primordial and preantral follicles to the gonadotrophin-dependent stages. We suggest that treatment with hGH prior to menotropin administration may be useful to improve results for poor responders to gonadotrophins.

Clinical Protocols↗
PubMed1997

Non-response to ovarian stimulation in normogonadotrophic, normogonadal women: a clinical sign of impending onset of ovarian failure pre-empting the rise in basal follicle stimulating hormone levels.

The most important aspect of diminished ovarian reserve is the associated decline in reproductive potential. Assessment of ovarian reserve is mainly based on measurement of early follicular phase follicle stimulating hormone (FSH) concentration. The objective of this study was to report the identification of a group of 12 infertile women initially diagnosed as having unexplained or anovulatory infertility, who had a normal baseline hormonal profile and did not respond to repeated ovarian stimulation with gonadotrophins. All developed ovarian failure within a relatively short time span. Non-response to ovarian stimulation was defined by failure to achieve development of follicles >12 mm and failure to raise oestradiol concentration >350 pmol/l in two successive cycles of human menopausal gonadotrophin (HMG) doses of up to five ampoules per day for 5-8 days. Within a mean of 9 months following the failed attempts of ovarian stimulation the mean day 3 FSH concentrations rose from 5.4 +/- 2.7 IU/l to 53.5 +/- 19.7 IU/l. In these patients, day 3 FSH concentration failed to indicate the low ovarian reserve manifested only by lack of clinical response to treatment with gonadotrophins which was the first sign of impending ovarian failure. We conclude that women with normal early follicular phase serum FSH concentrations who do not respond to ovarian stimulation by HMG are at risk of developing ovarian failure within several months.

Adult↗
PubMed1996

Induction of ovulation in clomiphene-resistant polycystic ovary syndrome with pulsatile GnRH.

OBJECTIVE: To determine the efficacy of pulsatile GnRH alone and in combination with clomiphene citrate or gonadotropins in a stepwise approach for inducing ovulation in women with clomiphene-resistant polycystic ovary syndrome (PCOS). METHODS: Eighty women with clomiphene-resistant anovulatory infertility and PCOS were given subcutaneous pulsatile GnRH (15 micrograms every 90 minutes) using a portable infusion pump. If no follicular development was seen, clomiphene citrate (100 mg/day for 5 days) was given concurrently with the hormone in the next cycle of treatment. Those who still failed to ovulate regularly were treated with combined pulsatile GnRH with intramuscular gonadotropins (one ampule per day for 5-7 days). RESULTS. Sixty-six of 131 (50%) pulsatile GnRH cycles, 94 of 142 (66%) pulsatile GnRH with clomiphene cycles, and 48 of 69 (70%) pulsatile GnRH with gonadotropin cycles were ovulatory. Monofollicular response (one follicle at least 14 mm on the day of ovulation) occurred in 80.6, 83.9, and 53.6% of cycles, and multifollicular response occurred in 4.8, 3.1, and 21.6% of cycles in the three groups, respectively. Mild ovarian hyperstimulation occurred in one of the 342 cycles. The cumulative conception rate was 30% after three cycles, 60% after six cycles, and 73% after nine cycles. The miscarriage rate was 22% (ten of 45 pregnancies), and 35 women (78%) had live births (33 singletons and two sets of twins). CONCLUSION: The use of subcutaneous pulsatile GnRH alone and in combination with clomiphene citrate or gonadotropins for induction of ovulation in clomiphene-resistant PCOS in a stepwise approach produces a high cumulative conception rate associated with a low rate of multiple pregnancy and ovarian hyperstimulation syndrome.

Adult↗
PubMed1996

Polycystic ovary syndrome: induction of ovulation.

In summarizing the treatment of infertility associated with PCOS, basically the induction of ovulation may be achieved by boosting FSH stimulation of the ovaries, either indirectly with clomiphene or native pulsatile GnRH, or directly with gonadotrophin preparations. There seem to be two main determinants of the success of this treatment in achieving a live birth: the degree of hyperinsulinaemia and the concentration of circulating LH. Either of these, when in excess, not only makes induction of ovulation and conception relatively difficult but is also associated with a high rate of early miscarriage. Their correction, particularly in obstinate cases, should be a major consideration in the attempt to achieve optimal results. With such a range of reasonably successful treatments for the induction of ovulation in PCOS, the emphasis in the selection of therapy should now be placed on minimizing the prevalence of undesired side-effects while retaining acceptable efficiency.

Anovulation↗
PubMed1996

Polycystic ovary syndrome - from gynaecological curiosity to multisystem endocrinopathy.

Recent progress in the diagnosis, pathophysiology, long-term ramifications and treatment of polycystic ovary syndrome has been rapid but the pathogenesis remains a challenging enigma and the treatment symptomatic. Objective ultrasound criteria for diagnosis are being formulated and have enabled an appreciation of the true prevalence and the associated clinical and biochemical manifestations. Although a heterogeneous syndrome, the final common pathway seems to involve a dysregulation of enzymes responsible for ovarian androgen biosynthesis, possibly influenced by insulin, growth factors and luteinizing hormone. A single gene defect, inherited in an autosomal dominant pattern, has been proposed. The treatment is necessarily symptomatic, depending on the needs of the patient. Long-term deleterious sequelae now emerging may demand suppression of the syndrome earlier in life. As the most prevalent cause of anovulatory infertility, a further elucidation of the basic pathogenesis is needed to allow the application of more specific and successful modalities of treatment.

Female↗
PubMed1996

Serum levels of insulin-like growth factor-1, IGF binding protein-1 and insulin and the response to human menopausal gonadotrophins in women with polycystic ovary syndrome.

In order to determine which factors influence the large variations in sensitivity to gonadotrophins witnessed in women with polycystic ovary syndrome (PCOS), a prospective study was conducted of the correlation between basal clinical and endocrinological features and gonadotrophin requirements of 20 women with clomiphene-resistant PCOS undergoing ovulation induction. Baseline evaluation of serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, fasting insulin, insulin-like growth factor-1 (IGF-1), IGF binding protein-1 (IGFBP-1) and sex hormone-binding globulin (SHBG) were performed before administering gonadotrophin-releasing hormone agonist (GnRHa). Two weeks later, human menopausal gonadotrophin (HMG) was given in a standard individualized protocol according to ovarian response, until human chorionic gonadotrophin (HCG) was given. Serum concentrations of insulin, IGF-1, and IGFBP-1 were unaffected by GnRHa. The BMI correlated positively with insulin and inversely with IGFBP-1 serum concentrations and insulin and IGFBP-1 were inversely correlated. The amount of HMG required correlated positively with BMI and insulin concentrations and inversely with IGFBP-1 in the whole group and these correlations were maintained in the sub-group of lean women. No correlation was observed between HMG requirements and IGF-1 or other hormones. Women with hyperinsulinaemia and low IGFBP-1 concentrations required significantly more HMG. Multiple regression analysis revealed that insulin concentration is the most significant determinant of HMG requirement even when dissociated from BMI. We concluded that requirements of HMG in PCOS is not merely determined by obesity but by a cardinal role of insulin concentrations which, when high, induce, hypothetically, a hyperandrogenic intrafollicular milieu.

Adult↗
PubMed1996

Severe ovarian hyperstimulation syndrome despite low plasma oestrogen concentrations in a hypogonadotrophic, hypogonadal patient.

Ovarian hyperstimulation syndrome (OHSS) is the most serious, life-threatening, iatrogenic complication of ovulation induction. The importance of excessive oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration as a predictor and factor in the pathophysiology of OHSS has been extensively studied and discussed. We present the case report of a woman with hypogonadotrophic hypogonadism who developed severe OHSS during ovulation induction with urinary human follicle stimulating hormone (FSH) and HCG in the presence of low circulating oestradiol concentrations. The implication of FSH treatment and complications in hypogonadotrophic hypogonadal patients, and the role of preovulatory oestradiol concentrations in the prediction of OHSS, are discussed.

Adult↗
PubMed1996

Growth hormone and fertility--clinical studies.

The linkage between the reproductive and somatotropic axes and the existence of a complex regulating system within the ovary involving growth factors and their binding proteins suggest that the ovary may be a target of growth hormone (GH) action. Clinical studies investigating possible applications of adjuvant GH treatment in ovulation induction and in vitro fertilization, mainly directed at poor responders to gonadotropin therapy, have shown that results are dependent on the hormonal status and 'ovarian age' of the subject. Additive GH is capable of increasing the sensitivity of ovaries to gonadotropins in those with a blatant or subtile lack of GH but not in those with a normal, saturated system. Improved pregnancy rates have not been convincingly forthcoming and more research is needed on the effect of GH and growth factors on the oocyte and endometrium. Disturbed GH kinetics in the polycystic ovary syndrome have prompted investigations of possible involvement of GH in the pathophysiology of this syndrome.

Anovulation↗
PubMed1995

A comparative prospective study of conventional regimen with chronic low-dose administration of follicle-stimulating hormone for anovulation associated with polycystic ovary syndrome.

OBJECTIVE: To compare efficiency of conventional and chronic low-dose regimens for treatment of anovulation associated with polycystic ovary syndrome (PCOS). DESIGN: Fifty participants divided into two equal groups. The first group was treated with urinary human FSH using a conventional stepwise protocol and the second group was treated with a regimen of chronic low-dose and small incremental rises with urinary human FSH or with recombinant human FSH for a maximum of three cycles. SETTING: Tertiary referral university hospital fertility unit. PATIENTS: Fifty infertile women with clomiphene citrate-resistant anovulation associated with PCOS. MAIN OUTCOME MEASURES: Pattern of follicular development, amount of FSH required, serum E2 concentrations, cycle fecundity, cumulative conception, and live birth rates. Multiple pregnancy and ovarian hyperstimulation syndrome (OHSS) rates. RESULTS: Compared with the conventional dose protocol, the chronic low-dose regimen yielded slightly improved pregnancy rates (40% versus 24%) while completely avoiding OHSS and multiple pregnancies, which were prevalent (11% and 33%, respectively) with conventional therapy. Monofollicular development was induced in 74% versus 27% of cycles, and the total number of follicles > 16 mm and E2 concentrations were half those observed on conventional therapy. CONCLUSIONS: For women with PCOS, a chronic low-dose regimen of FSH eliminated complications of OHSS and multiple pregnancies while maintaining a satisfactory pregnancy rate. This modality, thus, has distinct advantages and could well replace conventional gonadotropin therapy for these patients.

Adult↗
PubMed1995

Polycystic ovary syndrome patients as oocyte donors: the effect of ovarian stimulation protocol on the implantation rate of the recipient.

OBJECTIVE: To evaluate the outcome of oocytes donated by women with polycystic ovarian syndrome (PCOS) compared with oocytes donated by women with mechanical infertility. DESIGN: A retrospective study. PATIENTS: The outcome of 159 oocyte donation cycles with oocyte donated by PCOS patients were compared with 69 oocyte donation cycles with oocytes donated by patients with mechanical infertility. We compared the stimulation protocols in the donors to assess if the combination of GnRH analogue (GnRH-a), FSH, and hMG has an advantage over FSH and hMG alone with respect to their effect on fertilization and implantation rates in oocyte donation cycles. RESULTS: When treated with GnRH-a, pregnancy rates in PCOS and mechanical infertility donors were higher than those treated with FSH and hMG alone. The comparison between PCOS and mechanical factor oocyte recipients revealed no significant difference in the pregnancy and abortion rates, but the oocytes of patients with PCOS that were exposed to GnRH-a had a significantly higher implantation rate than those not exposed to GnRH-a. CONCLUSIONS: Oocytes obtained from PCOS patients had a fertilization potential equal to oocytes obtained from mechanical infertility donors. Furthermore, because the oocytes of patients with PCOS exposed to GnRH-a had a significantly higher implantation rate, a detrimental role of high LH on oocyte quality seems probable. However, because PCOS has a high familial prevalence, some reservations may arise due to a possible propagation of the problem in the next generation of oocyte donation programs.

Embryo Implantation↗
PubMed1995

Clinical applications of growth hormone for ovarian stimulation.

The realization of the existence of an intra-ovarian regulating mechanism involving insulin-like growth factor-I (IGF-I), a mediator of growth hormone (GH) action that augments the ovarian response to gonadotrophins, has prompted a number of clinical trials exploring the use of GH as an adjuvant for ovarian stimulation with human menopausal gonadotrophin. A critical review of these studies pinpoints a select group of infertile patients who may benefit from this co-treatment, particularly those who have a surgical, pathological or medically induced dysfunction of GH kinetics. The mechanism of this action, the effective dose needed and the implications regarding the interface of GH, IGF-I and ovarian physiology and pathology are now becoming clearer. A greater understanding of GH action on the ovary may in future benefit patients afflicted by anovulatory infertility and those requiring ovulation induction for in-vitro fertilization.

Clinical Trials as Topic↗
PubMed1995

Adjuvant growth hormone for induction of ovulation with gonadotrophin-releasing hormone agonist and gonadotrophins in polycystic ovary syndrome: a randomized, double-blind, placebo controlled trial.

The objective of this study was to explore the effect of cotreatment with recombinant human growth hormone (GH), gonadotrophin-releasing hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG) for induction of ovulation in women with clomiphene resistant polycystic ovary syndrome (PCOS). It was designed as a randomized, double-blind, placebo controlled trial in which 30 women with anovulation associated with PCOS who were resistant to clomiphene all received DTRP6-LHRH (Decapeptyl microcapsules, 3.75 mg, i.m.) and, 2 weeks later, HMG in a standard, conventional, individually adjusted dose regimen until human chorionic gonadotrophin (HCG) and then luteal phase support could be given. From day 1 of HMG therapy, patients were randomized to receive either human GH (Norditropin, 12 IU/day, i.m., for 7 days) or placebo. The number of ampoules, duration of treatment and daily effective dose of HMG required to achieve ovulation, serum oestradiol concentrations and number of follicles induced, ovulation and pregnancy rates, serum insulin and insulin-like growth factor-I (IGF-I) concentrations were measured. There were no significant differences between growth hormone and placebo groups in any of the outcomes measured, other than a growth hormone induced increase in serum insulin and IGF-I levels. We conclude that although GH kinetics are abnormal and GH pituitary reserves generally low in women with PCOS, adjuvant GH treatment to GnRHa/HMG does not influence follicular development or sensitivity in response to gonadotrophins and that it does not seem likely to be of any potential clinical benefit for the treatment of PCOS.

Adult↗
PubMed1995

Growth hormone and reproduction.

It has become apparent that the reproductive and somatotrophic axes may often be interlinked, and that the ovary may be a target for growth hormone action. Within the ovary, there exists a complex regulating system involving growth factors, which promote gonadotrophin action, and their binding proteins, which modulate these actions. The realization of the existence of this fine-tuning system has prompted clinical trials of cotreatment with growth hormone and gonadotrophins, mainly directed at the poor responder to gonadotrophin stimulation. The effect of this treatment is dependent on the hormonal status and 'ovarian age' of the patient. Studies have delineated a possible role for additional growth hormone in those with a lack of growth hormone but it has little place in a normal system. Although an improvement in pregnancy rate has not yet emerged, more research should be forthcoming on the effect of growth hormone and growth factors on the follicle, oocyte and endometrium and their possible role in polycystic ovary syndrome.

Clinical Trials as Topic↗
PubMed1993

Gonadotropin-releasing hormone agonist reduces the miscarriage rate for pregnancies achieved in women with polycystic ovarian syndrome.

OBJECTIVE: To compare the effect of treatment with gonadotropin-releasing hormone agonist (GnRH-a) and human menopausal gonadotropins (hMG) with that of gonadotropins only, on the cumulative livebirth rate and miscarriage rate of pregnancies achieved in women with polycystic ovarian syndrome (PCOS). DESIGN: Retrospective analysis of the outcome of 97 pregnancies according to the treatment protocol, with or without GnRH-a. Calculation of miscarriage rate and cumulative livebirth rate by life-table analysis. SETTING: Infertility clinic and in vitro fertilization (IVF) unit. PATIENTS: Women with polycystic ovaries (n = 239) who were clomiphene citrate failures and received either GnRH-a/hMG (n = 110) or gonadotropins only (n = 129) for ovulation induction (n = 138) or superovulation for IVF (n = 101). INTERVENTIONS: For ovulation induction, hMG was given in a step-up, individually adjusted dose scheme. For IVF, three ampules of pure follicle-stimulating hormone were given for 3 days followed by three ampules per day hMG and then individual dose adjustment. Gonadotropin-releasing hormone agonist (Decapeptyl, D-Trp6, microcapsules, 3.75 mg) was given in a single dose 2 weeks before gonadotropin treatment. MAIN OUTCOME MEASURES: The rate of early miscarriages (< 12 weeks) per pregnancies achieved was analyzed, and the cumulative livebirth rate for each treatment group was calculated by life-table analysis. RESULTS: Miscarriage rates after treatment in ovulation induction with (16.7%) and without GnRH-a (39.4%) and in IVF with (18.2%) and without GnRH-a (38.5%) were almost identical and were therefore analyzed together. Of pregnancies achieved with GnRH-a, 17.6% miscarried compared with 39.1% of those achieved with gonadotropins alone. Cumulative livebirth rate after four cycles for GnRH-a was 64% compared with 26% for gonadotropins only. CONCLUSIONS: Cotreatment with GnRH-a/hMG for anovulatory women with PCOS reduces the miscarriage rate and improves the livebirth rate compared with treatment with gonadotropins alone.

Abortion, Spontaneous↗