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Biomedical subjects

Cornelis B Lambalk

Publications and source records attributed to Cornelis B Lambalk.

At least 19 recordsLinked to original sources
PubMed2006

Consequences of infertility in developing countries: results of a questionnaire and interview survey in the South of Vietnam.

BACKGROUND: This study explores the psychological, socio-cultural and economic consequences of infertility on couples' life. The purpose of this research is to improve knowledge about the potentially serious implications of infertility in the South of Vietnam. METHODS: This study included 118 infertile couples who filled in questionnaires and 28 men and women who were interviewed. RESULTS: Data of the questionnaire show men and women do not differ in their responses and attitudes towards infertility. Almost one-third of the participants require psychological support. Interviewees experience secrecy, social pressure and economic hardship. CONCLUSION: Offspring are very important to Vietnamese couples. Their future depends on children. Family plays an important role in the experiences of the infertile couple. Economic consequences are a particular distressing factor. There is a need for psychological counselling in the treatment of infertile couples in the South of Vietnam. It should be realised that in developing countries, despite overpopulation, unwanted childlessness is an important social and economical burden that needs attention.

Journal Article↗
PubMed2006

Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial.

OBJECTIVE: To compare the effectiveness of clomifene citrate plus metformin and clomifene citrate plus placebo in women with newly diagnosed polycystic ovary syndrome. DESIGN: Randomised clinical trial. SETTING: Multicentre trial in 20 Dutch hospitals. PARTICIPANTS: 228 women with polycystic ovary syndrome. INTERVENTIONS: Clomifene citrate plus metformin or clomifene citrate plus placebo. MAIN OUTCOME MEASURE: The primary outcome measure was ovulation. Secondary outcome measures were ongoing pregnancy, spontaneous abortion, and clomifene resistance. RESULTS: 111 women were allocated to clomifene citrate plus metformin (metformin group) and 114 women were allocated to clomifene citrate plus placebo (placebo group). The ovulation rate in the metformin group was 64% compared with 72% in the placebo group, a non-significant difference (risk difference - 8%, 95% confidence interval - 20% to 4%). There were no significant differences in either rate of ongoing pregnancy (40% v 46%; - 6%, - 20% to 7%) or rate of spontaneous abortion (12% v 11%; 1%, - 7% to 10%). A significantly larger proportion of women in the metformin group discontinued treatment because of side effects (16% v 5%; 11%, 5% to 16%). CONCLUSION: Metformin is not an effective addition to clomifene citrate as the primary method of inducing ovulation in women with polycystic ovary syndrome. TRIAL REGISTRATION: Current Controlled Trials ISRCTN55906981 [controlled-trials.com].

Adult↗
PubMed2006

The clomiphene citrate challenge test versus the exogenous follicle-stimulating hormone ovarian reserve test as a single test for identification of low responders and hyperresponders to in vitro fertilization.

OBJECTIVE: This study was designed to compare the exogenous FSH ovarian reserve test (EFORT) versus the clomiphene citrate challenge test (CCCT), basal FSH, and basal inhibin B, with respect to their ability to predict poor and/or hyperresponders in an IVF population. DESIGN: Prospective randomized controlled trial. SETTING: Fertility center of a university hospital. PATIENT(S): One hundred ten patients undergoing their first IVF cycle, randomized into two groups. INTERVENTION(S): Fifty-six patients underwent a CCCT, and 54 patients underwent an EFORT. In all patients, the test was followed by an IVF treatment. MAIN OUTCOME MEASURE(S): Ovarian response, expressed by the total number of retrieved oocytes. RESULT(S): Univariate logistic regression showed that the best predictor for poor response is the CCCT (area under receiver operator characteristic curve [ROC-AUC] = 0.87), with maximal accuracy of 0.89. Multiple logistic regression analysis did not produce a better model in terms of improving the prediction of poor response. For hyper response, univariate logistic regression showed that the best predictor is the inhibin B increment in the EFORT (ROC-AUC = 0.92) but with a low maximal accuracy of 0.78. Again, multiple logistic regression analysis did not produce a better model in terms of predicting hyper response. CONCLUSION(S): Our study, the first which compares the CCCT with the EFORT for the prediction of poor and hyperresponders, shows that the CCCT is superior for identification of low responders. The EFORT (inhibin B increment) is superior for prediction of hyper response at the cost of a high rate of false positives. Neither of the two tests seems adequate to act alone for identification of both poor and hyperresponders.

Clomiphene↗
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↗
PubMed2006

Effect of an oral contraceptive pill on follicular development in IVF/ICSI patients receiving a GnRH antagonist: a randomized study.

This randomized controlled study compared the effectiveness of a gonadotrophin releasing hormone (GnRH) antagonist protocol with or without oral contraceptive (OC) pretreatment on the number of oocytes retrieved in IVF or intracytoplasmic sperm injection (ICSI) patients. Sixty-four patients were randomized to start recombinant human FSH (r-hFSH) on day 2 or 3 after OC withdrawal (OC group) or on day 2 of a natural cycle (control group). From stimulation day 6 onwards, all patients were treated with daily (0.5 mg/ml) GnRH antagonist (Antide). OC pretreatment resulted in significantly lower starting concentrations of FSH, LH and oestradiol (P < 0.001) and a thinner endometrium (P < 0.0001). In the early stimulation period, fewer large follicles were found after OC pretreatment, leading to a significantly extended stimulation period (11.6 versus 8.7 days, P < 0.0001) with more follicles on the day of recombinant human chorionic gonadotrophin administration (15.4 versus 12.5, P = 0.02) and more oocytes retrieved (13.5 versus 10.2, P < 0.001) as compared with the control group. GnRH antagonist regimen, pretreated with OC, prevented the early endogenous FSH rise and improved follicular homogeneity, resulting in more oocytes. As a consequence of the extended treatment period, more rhFSH was required.

Adult↗
PubMed2005

Comparison of serum FSH and Inhibin B levels between adult male dizygotic and monozygotic twins.

BACKGROUND: FSH hypersecretion occurs in mothers of dizygotic (DZ) twins. Twinning is inherited via both sexes and transmitted through the female. FSH hypersecretion may thus occur in male DZ twins. METHODS: We assayed FSH and its counter-regulatory hormone, Inhibin B, in 108 adult male DZ and 100 monozygotic (MZ) twins (as controls) and compared our results to published norms. RESULTS: Inhibin B was elevated and higher in DZ compared with MZ twins with similar FSH. CONCLUSION: The normal FSH: Inhibin B endocrine feedback axis is different in adult male DZ twins. This contributes to the theory that the answer to human DZ twinning lies in the actions of FSH and Inhibin, and in their mutual interaction.

Adult↗
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

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

Growth hormone secretion is impaired but not related to insulin sensitivity in non-obese patients with polycystic ovary syndrome.

BACKGROUND: The aim of the study was to elucidate the relationship between growth hormone (GH) secretion and insulin resistance in polycystic ovary syndrome (PCOS) patients. In order to exclude the influence of obesity on these parameters, only non-obese PCOS patients were studied. METHODS: Eleven PCOS patients and 11 controls with a body mass index (BMI) </= 25 kg/m2 were studied. PCOS patients were studied on cycle day 14-15, controls on cycle day 5-9. GH secretion was determined by frequent sampling, from 20.00 h to 08.00 h. Insulin sensitivity was determined by a euglycaemic hyperinsulinaemic clamp and was expressed as the M-value. Insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) levels were determined once. RESULTS: Pooled GH levels were significantly lower in PCOS patients than controls, as was GH pulse amplitude. The number of GH pulses was not different between PCOS patients and controls. The M-value was significantly lower in PCOS patients, although a wide overlap between patients and controls was present. IGF-1 and IGFBP-3 levels were not different between the groups. There was no correlation between the M-value and pooled GH or IGF-1 and IGFBP-3 levels. CONCLUSION: Non-obese patients with PCOS have impaired GH secretion and some but not all have impaired insulin sensitivity. These findings indicate that these patients may also be at risk for cardiovascular diseases and/or diabetes mellitus.

Area Under Curve↗
PubMed2004

Influence of varicocele embolization on the choice of infertility treatment.

OBJECTIVE: To investigate whether embolization of a varicocele improves semen quality and enables use of less-invasive modes of assisted reproductive technology (ART) in infertile men with a physically palpable varicocele confirmed by phlebography. DESIGN: Retrospective chart review. SETTING: University infertility clinic. PATIENT(S): Fifty patients with varicoceles that were treated with embolization and 11 patients with untreated varicoceles (control group). In both groups the clinical varicoceles had been phlebographically confirmed. INTERVENTION(S): Phlebography and embolization. MAIN OUTCOME MEASURE(S): Semen characteristics and mode of ART before and after treatment. RESULT(S): Median improvements of semen parameters, such as concentration and motility after processing, were significantly greater in the embolization group than in the untreated group. In the embolization group, semen samples improved to levels requiring less-invasive modes of ART in significantly more patients than in the untreated group. Deterioration of semen samples, requiring more invasive techniques, was significantly more frequent in the untreated group than in the embolization group. CONCLUSION(S): Embolization of a varicocele in infertile men significantly improved semen, such that much more often a less-invasive form of ART than was planned before treatment became feasible. Embolization of a varicocele might even prevent further deterioration of semen samples to levels requiring more-invasive ART.

Adult↗
PubMed2004

Estimation of the follicle-stimulating hormone (FSH) threshold for initiating the final stages of follicular development in women with elevated FSH levels in the early follicular phase.

OBJECTIVE: To test the hypothesis that the follicle-stimulating hormone (FSH) threshold in patients with elevated FSH levels in the early follicular phase (EFP) is higher than in controls. DESIGN: Pilot study. SETTING: Academic hospital. PATIENT(S): Six patients with elevated EFP FSH (>10 IU/L) and 13 controls. INTERVENTION(S): Treatment with a GnRH agonist in the midluteal phase before IV administration of recombinant FSH was started in an ultra-low-dose step-up protocol. The FSH threshold was determined by the mean of FSH levels of the above threshold value and the below threshold value. MAIN OUTCOME MEASURE(S): Follicle-stimulating hormone threshold, FSH screening value, E(2), number of follicles. RESULT(S): The FSH threshold in the elevated EFP FSH group was 6.75 IU/L and was significantly higher than the FSH threshold of the controls (4.65 IU/L). The FSH screening value on day 3 was 12.0 IU/L in the patient group and 5.0 IU/L in the controls. Estradiol was significantly lower on the day that the largest follicle was 18 mm in the elevated EFP FSH group compared with controls (277 vs. 491 pmol/L, respectively). On the day of hCG administration, the number of smaller (10-13 mm) follicles was equal but the number of larger (>14 mm) follicles was higher in the control group compared with the elevated FSH group. In the control group, the basal FSH levels correlated highly with the FSH threshold levels (r = 0.8), but in the patients with elevated EFP FSH this correlation was absent. CONCLUSION(S): In normal women, basal FSH day 3 values represent the ovarian threshold for FSH. In women with elevated day 3 FSH, the FSH threshold is higher but not as high as basal FSH values. We postulate that the FSH threshold in patients with elevated EFP FSH is higher because of intraovarian factors. Basal FSH overshoots the threshold, probably because of the limited feedback by the ovary.

Chorionic Gonadotropin↗
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↗
PubMed2004

Contemporary pharmacological manipulation in assisted reproduction.

Follicle-stimulating hormone (FSH) treatment to induce follicular development in anovulating women and multiple follicular development for assisted conception has been incorporated in almost all reproductive treatment cycles in the form of either urinary, purified urinary or recombinant preparations. Besides improved tolerance and theoretically lower chances of infection by prions, the latter may be more effective in terms of clinical pregnancy rates, FSH requirement and cost effectiveness. The low-dose, step-up protocol to induce monofollicular development, which is applied worldwide, has to compete with the equally effective but health economically beneficial step-down protocol. The long protocol using recombinant FSH 150 IU/day is advocated when using gonadotropin-releasing hormone (GnRH) agonists in in vitro fertilisation (IVF) or intracytoplasmatic sperm injection treatment. However, the current paradigmatic hyperstimulation came under scrutiny after the introduction of the GnRH antagonists, which allow milder and more convenient approaches with acceptable cancellation and pregnancy rates but lower requirements for FSH. Risk of ovarian hyperstimulation syndrome (OHSS) can be further eliminated if recombinant luteinising hormone (rLH) or GnRH agonists are used to trigger oocyte maturation and ovulation; the latter require pituitary responsiveness and are therefore excluded in agonist protocols. FSH and LH are both required for appropriate folliculo- and steroidogenesis. In hypogonadotropic women, the addition of LH (human menopausal gonadotropin, human chorionic gonadotropin or rLH) is therefore obligate to achieve appropriate follicular growth and pregnancy. The role of LH in ovulation induction is still a matter of debate, although in GnRH agonistic protocols there seems to be a 'therapeutic window'; levels that are too high or too low have detrimental effects on IVF outcome. To broaden the pharmaceutical armoury, recent efforts have been directed towards the development of novel GnRH antagonists and FSH preparations with optimal pharmacokinetic, pharmacodynamic and safety profiles. Alternative strategies with fewer adverse effects and higher benefit/cost ratios are under development. However, before the GnRH agonist is abandoned for the antagonist as standard therapy, the cause of the observed possible lower pregnancy rates with the latter need to be clarified. In addition, prospective studies investigating possible direct effects of GnRH analogues, optimal dose-finding studies and treatment regimens under different conditions, with or without pharmacological coadministration and for different indications, should be performed to optimise the efficacy and tailor treatment strategies to individual needs.

Clinical Trials as Topic↗
PubMed2003

Accuracy of diagnostic laparoscopy in the infertility work-up before intrauterine insemination.

OBJECTIVE: To evaluate the accuracy of diagnostic laparoscopy after normal hysterosalpingography (HSG) and before intrauterine insemination (IUI) with respect to laparoscopic findings leading to a change of treatment decisions in couples with male subfertility, cervical hostility, or idiopathic infertility. DESIGN: Retrospective chart review. SETTING: University medical centre. PATIENT(S): Infertility patients who had undergone diagnostic laparoscopy after a normal HSG and before IUI in a period of 5 years. INTERVENTION(S): Diagnostic laparoscopy in infertility work-up before IUI. MAIN OUTCOME MEASURE(S): Prevalence of laparoscopic findings leading to change in treatment decision. RESULT(S): Of 495 patients, 21 (4%) had severe abnormalities that resulted in a change of treatment to in vitro fertilization or open surgery. In 103 patients (21%) abnormalities, endometriosis (stages I and II), and adhesions were directly treated by laparoscopic intervention, followed by IUI treatment. If surgery to remove early stage endometriosis does not improve pregnancy rates, then the laparoscopic yield would be 40 out of 495 (8.1%). CONCLUSION(S): Diagnostic laparoscopy altered treatment decisions in an unexpectedly high number of patients before IUI. This suggests that laparoscopy may be of considerable value, provided the change in treatment is effective. Further prospective studies are required to assess whether the diagnostic use of laparoscopy is cost effective and whether interventions as result of laparoscopic findings are effective in improving pregnancy rates.

Cervix Uteri↗
PubMed2003

Investigation of the infertile couple: should diagnostic laparoscopy be performed in the infertility work up programme in patients undergoing intrauterine insemination?

Diagnostic laparoscopy is normally the standard procedure performed as the final test in the infertility work up before progressing to infertility treatment. Recently, there has been a growing tendency to bypass diagnostic laparoscopy after a normal hysterosalpingogram and instead to start direct infertility treatment [intrauterine insemination (IUI) or IVF] for indications such as unexplained infertility, male subfertility and cervical hostility. In our clinic, laparoscopy revealed abnormalities that resulted in changed treatment decisions in 25% of the patients who would normally have been scheduled for IUI if laparoscopy had not been performed. The changed treatments mainly concerned surgery for minimal/mild endometriosis and periadnexal adhesions, both performed during the diagnostic laparoscopy. Because the effect of such interventions on the success rate of IUI has never been described, it still remains unclear whether laparoscopy is usefully performed in these cases. Therefore, further prospective studies should be performed to assess whether delaying, or bypassing entirely, diagnostic laparoscopy is more cost effective and if laparoscopic interventions for intra-abdominal abnormalities are effective in terms of higher pregnancy rates after treatment with IUI.

Endometriosis↗
PubMed2002

GnRH agonists, antagonists, and assisted conception.

Pituitary stimulation with pulsatile gonadotropin-releasing hormone (GnRH) induces both follicle-stimulating hormone and luteinizing hormone (LH). Blockade of pituitary gonadotropin secretion occurs upon desensitization when a continuous GnRH stimulus is provided by means an agonist or when the pituitary receptors are occupied with a competitive antagonist. The most common indication for blockade of pituitary gonadotropin secretion is with assisted reproduction treatment (ART) where it prevents premature luteinization. Originally by lack of clinically available GnRH antagonist, prolonged daily injection of agonist with its desensitizing effect was introduced for this purpose. Today, single- and multiple-dose injectable antagonists are also available to block the LH surge. This review provides an overview of the use of GnRH agonists and antagonists in assisted reproduction.

Fertilization↗