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Biomedical subjects

Roy Homburg

Publications and source records attributed to Roy Homburg.

15 recordsLinked to original sources
PubMed2006

Optimizing hCG cut-off values: a single determination on day 14 or 15 is sufficient for a reliable prediction of pregnancy outcome.

OBJECTIVE: Optimizing the cut-off level for a single serum hCG determination around day 15 after oocyte retrieval or ovulation. STUDY DESIGN: Retrospective data analysis. RESULTS: 204 hCG samples >5 IU/L between March and October 1999 taken on day 14, 15 or 16 after oocyte retrieval in 204 patients undergoing IVF or ICSI were analyzed. ROC-curves and optimal cut-off levels to discriminate between viable and non-viable pregnancies were calculated for each day separately. Cut-off levels were found at 76, 142 and 223 IU/L for day 14, 15 and 16, respectively, and were verified by 487 hCG samples >5 IU/L taken between January 2000 and June 2004. CONCLUSIONS: A single serum hCG determination on day 14 or 15 is sufficient to discriminate viable pregnancies accurately from non-viable pregnancies.

Adult↗
PubMed2005

Clomiphene citrate--end of an era? A mini-review.

The purpose of this review is to examine whether the time has come to replace clomiphene citrate (CC) as the first line therapy for WHO group II (eu-oestrogenic) infertility, the majority of which is associated with polycystic ovary syndrome. CC has been the first line therapy for these cases for the last 40 years. It is a simple, cheap treatment, almost devoid of side effects which yields a single live birth rate of approximately 25% of starters. Non-response to CC and the gap between ovulation and pregnancy rates have variously been attributed to its anti-estrogen effects, and high LH and androgen concentrations. Three possible contenders for the replacement of CC as first-line treatment are scrutinized: metformin, aromatase inhibitors and low-dose FSH. Each has their advantages and disadvantages, but none of them, while showing much potential promise, has been proven, as yet, to be a feasible replacement for CC in this role. For CC, it may not yet be the end of an era but it may be the beginning of the end.

Clomiphene↗
PubMed2004

Dose-finding study of daily GnRH antagonist for the prevention of premature LH surges in IVF/ICSI patients: optimal changes in LH and progesterone for clinical pregnancy.

BACKGROUND: An optimal range of LH concentrations for achieving pregnancy has not been established. The aim of this study was to investigate the effect of various LH levels induced by different GnRH antagonist doses on IVF outcome. METHODS: This was a prospective, single centre study including 144 IVF patients, stimulated with recombinant FSH from cycle day 2, and co-treated with daily GnRH antagonist (antide/Iturelix) (2 mg/2 ml, 1 mg/ml, 0.5 mg/ml, 0.5 mg/0.5 ml or 0.25 mg/ml) from cycle day 7 onwards. Serum samples were taken three times daily. RESULTS: Clinical pregnancies were only observed within a particular range of change in LH levels. The upper and lower thresholds for the mean LH area under the curve (AUC), adjusted for the baseline LH level before the antagonist was started (LH AUC(-S6); S6=stimulation day 6) were -2.2 and 12.4 (IU/l) respectively (a negative value=below baseline levels). There were no clinical pregnancies outside these threshold values. Similar results were found for progesterone, the threshold levels of progesterone AUC(-S6) were 3.98 and -1.21 ng/ml. Moreover, there were no pregnancies with progesterone levels >0.26 ng/ml/follicle on the day of hCG. CONCLUSIONS: Excessive or insufficient suppression of LH and progesterone levels during GnRH antagonist administration and high progesterone/follicle on hCG day seems to be associated with impaired clinical pregnancy rates.

Adult↗
PubMed2004

Towards less confusing terminology in reproductive medicine: a counter proposal.

Less confusing terminology in reproductive medicine was the goal of a recent proposal the basis of which was to drop the term 'infertility' and replace it with a description. It also contained a prognostic grading system. The present article, arguing against most of these proposals, should not be regarded as nihilism but as constructive criticism to attain more clarity and common understanding. A counter proposal is suggested and includes retention of the term 'infertility', disposal of the terms 'subfertility' and 'sterility' with practical suggestions of when difficulties in conceiving should be investigated and treated.

Communication↗
PubMed2004

Dose-finding study of daily gonadotropin-releasing hormone (GnRH) antagonist for the prevention of premature luteinizing hormone surges in IVF/ICSI patients: antide and hormone levels.

BACKGROUND: The aim of this study was to define the minimal effective dose of antide (Iturelix) to prevent premature luteinizing hormone (LH) surges in in vitro fertilization (IVF) patients. METHODS: In a prospective, single centre study, 144 IVF/ICSI patients were stimulated with r-hFSH from cycle day 2 and from cycle day 6 onwards, cotreated with daily 2 mg/2 ml (n=30), 1 mg/ml (n=30), 0.5 mg/ml (n=31), 0.5 mg/0.5 ml (n=23) and 0.25 mg/ml (n=30) GnRH antagonist (antide). Serum samples were taken three times daily during antide administration to assess antide and hormone levels. The minimal effective dose was defined as the lowest dose group with <2 LH surges (LH >12.4 IU/l and progesterone >2 ng/ml). RESULTS: Serum antide levels, mean LH and E2 levels per day and their area under the curves were dose-related to antide. The bioavailability of antide almost doubled after dilution in larger volumes. Pre-injection LH levels gradually increased during GnRH antagonist treatment. LH surges occurred in the lowest dose groups 0.5 mg/ml (3.2%), 0.5 mg/0.5 ml (6.7%) and 0.25 mg/ml (13.3%). Hence, 0.5 mg/ml is considered to be the minimal effective dose. Antide was overall well tolerated and safe. CONCLUSIONS: 0.5 mg/ml antide is the minimal effective dose to prevent an untimely LH surge in IVF patients stimulated with r-hFSH.

Adult↗
PubMed2004

Polycystic ovary syndrome in adolescence--a therapeutic conundrum.

The polycystic ovary syndrome (PCOS) often presents in adolescence with menstrual disorders, acne and hirsutism. The early diagnostic signs are sometimes dismissed as 'normal' changes of adolescence, and the opportunity to save the teenager from the stigmata of the syndrome is missed. The finding that the metabolic syndrome is a possible long-term sequela of PCOS now presents a challenge to make an early diagnosis, educate patients regarding the importance of weight control and exercise, and treat accordingly both symptomatically and prophylactically. The use of long-term insulin sensitizers, particularly metformin, for these purposes in adolescents is now the subject of an inter-disciplinary debate. Good, hard supportive data are not yet forthcoming but, as in the adult, the establishment of metformin treatment for the hyperinsulinaemic adolescent with PCOS may precede the evidence.

Adolescent↗
PubMed2004

Management of infertility and prevention of ovarian hyperstimulation in women with polycystic ovary syndrome.

Anovulatory infertility is a prevalent presenting feature of polycystic ovary syndrome (PCOS). Restoration of ovulation might be achieved by ovarian stimulation or by reducing insulin and LH concentrations. Clomiphene citrate is the first-line ovulation-inducing agent, usually followed by direct stimulation with follicle stimulating hormone (FSH), if unsuccessful. The prevalent complications of ovarian hyperstimulation syndrome and multiple pregnancies can largely be avoided by administering FSH in a low dose and individualized regimen. Hyperinsulinaemia can be corrected by weight loss or insulin-sensitizing agents, such as metformin, which alone or in combination with other agents are capable of restoring ovulation. Advice about weight loss is critical in modern management of PCOS and infertility. Laparoscopic ovarian drilling produces similar results to FSH stimulation, and in vitro fertilization/embryo transfer (IVF/ET)-if all else fails-produces excellent results. The possible use of aromatase inhibitors, novel insulin sensitizers and in vitro maturation of oocytes is still being evaluated. The plethora of treatment options available today ensures that the great majority of women who are subfertile due to PCOS can be treated successfully.

Clomiphene↗
PubMed2004

Human embryo implantation: current knowledge and clinical implications in assisted reproductive technology.

A pregnancy rate of approximately 15% per cycle renders the process of human reproduction inefficient. The cycle-dependent expression of molecules involved in the embryo-endometrial dialogue has lead to the identification of a 'window of implantation'. This is the unique temporal and spatial expression of factors that allows the embryo to implant (via signalling, appositioning, attachment and invasion) in a specific time frame of 48 h, 7-10 days after ovulation. Integrin molecules, L-selectin ligands, mucin-1, heparin-binding epidermal growth factor and pinopodes are involved in appositioning and attachment. The embryo produces cytokines and growth factors [interleukins, prostaglandins, vascular endothelial growth factor (VEGF)] and receptors for endometrial signals (leukaemia inhibitory factor receptor, colony stimulating factor receptor, insulin-like growth factors and heparin binding epidermal growth factor receptor). The immune system plays an important role. Immunomodulatory factors such as glycodelin, inhibin and interleukin prevent a graft-versus-host reaction. Angiogenesis controlled by VEGF and prostaglandins is needed for formation of a receptive endometrium and a placenta. Identification of these factors has led to their use as markers of implantation that may identify defects causing subfertility. An ideal marker of implantation is sensitive and specific, and easy to obtain without disturbing implantation. Glycodelin and leukaemia inhibitory factor (serum) and integrins and pinopodes (biopsies) are promising candidates.

Embryo Implantation↗
PubMed2003

The management of infertility associated with polycystic ovary syndrome.

Polycystic ovary syndrome [PCOS] is the commonest cause of anovulatory infertility. Treatment modes available are numerous mainly relying on ovarian stimulation with FSH, a reduction in insulin concentrations and a decrease in LH levels as the basis of the therapeutic principles. Clomiphene citrate is still the first line treatment and if unsuccessful is usually followed by direct FSH stimulation. This should be given in a low dose protocol, essential to avoid the otherwise prevalent complications of ovarian hyperstimulation syndrome and multiple pregnancies. The addition of a GnRH agonists, while very useful during IVF/ET, adds little to ovulation induction success whereas the position of GnRH antagonists is not yet clear. Hyperinsulinemia is the commonest contributor to the state of anovulation and its reduction, by weight loss or insulin sensitizing agents such as metformin, will alone often restore ovulation or will improve results when used in combination with other agents. Laparoscopic ovarian drilling is proving equally as successful as FSH for the induction of ovulation, particularly in thin patients with high LH concentrations. Aromatase inhibitors are presently being examined and may replace clomiphene in the future. When all else has failed, IVF/ET produces excellent results. In conclusion, there are very few women suffering from anovulatory infertility associated with PCOS who cannot be successfully treated today.

Female↗
PubMed2003

The case for initial treatment with intrauterine insemination as opposed to in vitro fertilization for idiopathic infertility.

The recent questioning of the validity of evidence used by the Royal College of Obstetricians and Gynaecologists in recommending ovarian stimulation with intrauterine insemination (IUI) as an effective treatment for couples with unexplained infertility, has re-ignited the debate on what the initial treatment for idiopathic infertility should be. The current best available evidence is used here with the conclusion that the initial treatment for idiopathic infertility should be IUI as opposed to IVF. This conclusion is reached using the results of randomized controlled trials wherever possible, live birth rates rather than pregnancy rates and taking into account efficacy; complications, especially multiple pregnancy rates; patient compliance and cost efficiency. None of these factors indicate that a change of policy to use IVF as first-line treatment in lieu of IUI for unexplained infertility is justified.

Cost-Benefit Analysis↗
PubMed2003

Ovulation induction.

Anovulation, a common cause of female infertility, is a highly curable condition. Presented here is a simple treatment-orientated diagnostic scheme. Anovulatory women with low endogenous oestradiol and follicle stimulating hormone (FSH) are treated with either pulsatile gonadotrophin releasing hormone (GnRH) or gonadotropins, and women with eu-oestrogenic anovulation (mostly with polycystic ovarian syndrome; PCOS) have first-line treatment with clomiphene citrate (CC), possibly with metformin. If CC fails, FSH is administered using a chronic low-dose protocol with small incremental dose rises. A comparison of urinary with recombinant and pure FSH with luteinising hormone (LH) containing gonadotropins is made. Recombinant products are purer and more convenient for use but are expensive. LH content has little impact except in hypogonadotropic hypogonadism or severe pituitary suppression with GnRH analogues. Aromatase inhibitors, recombinant LH and long-acting FSH may find a future place in the armamentarium.

Anovulation↗
PubMed2002

What is polycystic ovarian syndrome? A proposal for a consensus on the definition and diagnosis of polycystic ovarian syndrome.

The criteria for diagnosis and definition of polycystic ovarian syndrome used by clinicians and investigators are almost as heterogeneous as the syndrome itself. This has confused and seriously hindered the clarification of the genetics, aetiology, clinical associations and assessment of treatment and later sequelae of the syndrome. This article proposes a consensus for a unifying balanced and practical working definition for use as a standard. The proposal incorporates confirmation of the diagnosis suggested by clinical symptoms by ultrasound, and the use of hormonal estimations if typical ultrasound features are not seen and for the purpose of defining subsets of the syndrome. This consensus proposal attempts to bridge the gap between predominately American biochemical marker-based diagnosis and predominately European reliance on ultrasound as a sine qua non for diagnosis. It has been deliberately designed to be simple, practical and cheap, and if universally adopted as a standard could contribute much to all future work involving this most prevalent of syndromes.

Acne Vulgaris↗
PubMed2002

Should patients with polycystic ovarian syndrome be treated with metformin? A note of cautious optimism.

Hyperinsulinaemia has proved to be a key link in the enigmatic generation of the symptoms of polycystic ovarian syndrome (PCOS), i.e. anovulatory infertility and the skin stigmata induced by hyperandrogenism. Regression of these symptoms may be achieved by reducing the hyperinsulinaemia. As obesity exaggerates the expression of the symptoms induced by hyperinsulinaemia, a low calorie diet and lifestyle change resulting in loss of weight for obese women with PCOS is capable of reversing these symptoms. Insulin-sensitizing agents, predominantly metformin, have been examined for their ability, in all patients with PCOS, to achieve similar beneficial changes to those induced by loss of weight in the obese. While the scientific value of many of these studies is questionable and solid evidence of efficiency and safety is not complete, the honourable intent of lowering high insulin levels in this way prompts the bottom line of this debate to strike a note of cautious optimism that insulin-sensitizing agents will be of some clinical usefulness both in the short-term aiding of infertility treatment and, possibly, in the prevention of the long-term sequelae for this troublesome and very prevalent condition.

Anovulation↗
PubMedDate not supplied

Ovulation induction in perspective.

It has been suggested recently that, in some quarters, IVF be offered as first-line therapy to all infertile couples, regardless of the type of infertility. Hence, the time was thought right to scrutinise the results and complications of ovulation induction for anovulatory infertile couples. In addition to examining the outcome of conventional treatment with gonadotrophins and clomiphene citrate, special attention has been paid to the suggested improvement of results by taking into account the influence of obesity and the use of a low-dose gonadotrophin protocol. The possible contribution of more recent additions to the armamentarium such as insulin sensitizers and aromatase inhibitors, although still at an infant stage, are promising. Attention has been given to the prevention and treatment of ovarian hyperstimulation syndrome. The use of intra-uterine insemination (IUI) as an adjuvant to induction of ovulation and controlled ovarian hyperstimulation (COH) is examined. The very firm conclusion has been reached that, taking into account efficiency, complication rate and cost of treatment, at this stage, women with hypogonadotrophic hypogonadism or polycystic ovary syndrome should be offered accepted methods of ovulation induction and that couples with 'unexplained' or 'multifactorial subfertility' should still be exposed to COH with IUI and only after the failure of these therapies, be offered IVF.

Aromatase Inhibitors↗