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Biomedical subjects

C B Lambalk

Publications and source records attributed to C B Lambalk.

At least 37 records · Page 2Linked to original sources

Basal FSH, estradiol and inhibin B concentrations in women with a previous Down's syndrome affected pregnancy.

BACKGROUND: Two recent studies reported elevated basal FSH concentrations in women with a history of aneuploid conceptions. However, it is not known whether these elevated basal FSH concentrations reflect depletion of the primordial follicle pool, or were caused by an increased secretory drive for FSH. METHODS: Inhibin B and estradiol concentrations were measured as indicators for depletion of the primordial follicle pool in women with a history of a Down's syndrome pregnancy and in controls. RESULTS: In the women with a history of a Down's syndrome pregnancy, there was a significant inverse correlation between basal FSH and inhibin B concentrations (P < 0.0001, 95% CI -0.26 to -0.56). In the control group, this correlation did not reach statistical significance. CONCLUSIONS: Our data indicate that the elevated basal FSH concentrations observed in women with a history of a Down's syndrome pregnancy are likely to reflect early depletion of the primordial follicle pool. Therefore, further research into the ovarian ageing process could provide more insight in the origination of chromosomal abnormalities during pregnancy.

Adult↗

Gonadotropin-releasing-hormone-receptor antagonists.

Pulsatile gonadotropin-releasing hormone (GnRH) stimulates the pituitary secretion of both luteinising hormone (LH) and follicle-stimulating hormone (FSH) and thus controls the hormonal and reproductive function of the gonads. Blockade of GnRH effects may be wanted for a variety of reasons-eg, to prevent untimely luteinisation during assisted reproduction or in the treatment of sex-hormone-dependent disorders. Selective blockade of LH/FSH secretion and subsequent chemical castration have previously been achieved by desensitising the pituitary to continuously administered GnRH or by giving long-acting GnRH agonists. Only recently have GnRH-receptor antagonists, that immediately block GnRH's effects, been developed for clinical use with acceptable pharmacokinetic, safety, and commercial profiles. In assisted reproduction, these compounds seem to be as effective as established therapy but with shorter treatment times, less use of gonadotropic hormones, improved patient acceptance, and fewer follicles and oocytes. All current indications for GnRH-agonist desensitisation may prove to be indications for a GnRH antagonist, including endometriosis, leiomyoma, and breast cancer in women, benign prostatic hypertrophy and prostatic carcinoma in men, and central precocious puberty in children. However, the best clinical evidence so far has been in assisted reproduction and prostate cancer.

Adult↗

Natural versus induced twinning and pregnancy outcome: a Dutch nationwide survey of primiparous dizygotic twin deliveries.

OBJECTIVE: To compare obstetrical outcome of twin pregnancies after assisted reproduction with that of natural twin pregnancies. DESIGN: Retrospective national database study. SETTING: Academic Medical Centre. PATIENT(S): One thousand ninety-three primiparous mothers registered in the Dutch National Birth Registry who gave birth to a dizygotic (DZ) twin (male/female) in 1994, 1995, and 1996. We compared 613 natural twin pregnancies and 480 twin pregnancies born after assisted reproduction. MAIN OUTCOME MEASURE(S): Gestational length, mode of delivery, mode of presentation of the children, birth weight, APGAR score, congenital anomalies, perinatal mortality rate, highest recorded maternal diastolic blood pressure, and maternal postpartum complications. RESULT(S): Rates of perinatal mortality and very premature parturition (<29 weeks) were lower in natural twin mothers. Overall, induced DZ twins were born 3.5 days earlier with a lower birth weight and APGAR score compared with controls. Rates of congenital anomalies and incidence of cesarean section were not different. The highest recorded diastolic blood pressure was lower in induced twinning with a 30% lower incidence of diastolic blood pressure >90 mm Hg. CONCLUSION(S): Obstetric outcome for induced DZ twin pregnancy is less optimal than in natural DZ twin pregnancy. Twinning in assisted reproduction is known for its contribution to the high rate of premature deliveries, but in addition being a subfertile patient undergoing treatment makes an intrinsic contribution to adverse events as well.

Adult↗

Is GnRH self-priming an obligatory feature of the reproductive cycle?

Insufficient suppression of LH (premature elevation) and FSH (prolonged release) give rise to blood concentrations which may cause damaging effects on oocyte viability and too many follicles respectively. During the surge, LH rises from low to high threshold values to initiate processes from initiation of the resumption of oocyte meiosis to the induction of ovulation. In general, it is thought that a dramatic increase in LH concentration is required to attain the high threshold for ovulation. A self-priming mechanism, by which gonadotrophin-releasing hormone (GnRH) enhances the LH (and FSH) responses to its own action, was thought to be responsible. However, normal LH surges in rats consist of <2-7% of the maximal pituitary releasing capacity. The physiological roles of LH and FSH favour a control mechanism that restrains their blood concentrations during most of the cycle. Ovarian proteins, e.g. inhibin and putative gonadotrophin-surge-inhibiting factor/attenuating factor (GnSIF/AF), are involved in this process. We argue that the increased pituitary LH responsiveness during the mid-cycle surge is not the result of a self-priming process that 'dramatically' increases the LH releasing capacity of the pituitary gland. This is probably due to elimination by GnRH of the inhibitory action of the putative ovarian proteins GnSIF/AF.

Animals↗

Are elevated FSH concentrations in the pre-conceptional period a risk factor for Down's syndrome pregnancies?

Recent publications have reported a relation between a decreased ovarian reserve and Down's syndrome pregnancies. Using the data of a case-control study into risk factors for a Down's syndrome pregnancy, we estimated the usefulness of pre-conceptional basal follicle stimulating hormone (FSH) screening (detection rate, false positive rate, positive and negative likelihood ratio, as well as the loss rate of unaffected pregnancies) to identify Down's syndrome pregnancies. The optimal detection rate of pre-conceptional basal FSH screening for Down's syndrome pregnancies was 14%, corresponding to a false positive rate of 5% and a positive likelihood ratio of 2.8. Incorporation of basal FSH screening into the regimen of first trimester serum screening followed by nuchal translucency measurement would increase the detection rate from 85 to 87%. However, basal FSH screening alone or in combination with other screening methods would cause an unacceptably high loss rate of unaffected pregnancies compared with current screening protocols, indicating that routine pre-conception basal FSH screening would not be useful to identify women at risk for a Down's syndrome pregnancy. However, when elevated basal FSH concentrations are diagnosed during subfertility evaluation, an elevated risk for a Down's syndrome pregnancy could be discussed with women who become pregnant.

Down Syndrome↗

Birth weight corrected for gestational age is related to the incidence of Down's syndrome pregnancies.

Three recent studies reported that early depletion of the primordial follicle pool is likely to be an independent risk factor for Down's syndrome pregnancies. The size of the primordial follicle pool at birth is determined by oogenesis and by the rate of follicle atresia during the intra uterine period. Since intra uterine growth retardation was reported to be associated with a significantly reduced primordial follicle pool at birth, we investigated the possibility of a relation between low birth weight for gestational age and the risk of a Down's syndrome pregnancy. In a case control study, 95 women with a history of a Down's syndrome pregnancy and 85 controls provided information on their own birth weight and length of gestation. Birth weight standard deviation scores, indicating the difference in birth weight from a reference group, were significantly lower in Down's syndrome mothers than in controls. These findings illustrate that the risk of a Down's syndrome pregnancy is related to a low birth weight corrected for gestational age, possibly by a causal relation between intra uterine growth retardation and the size of the primordial follicle pool.

Adult↗

Potential bias regarding birth weight in historical and contemporary twin data bases.

In this study we examine the hypothesis that monozygotic (MZ) twins in historical databases are less discordant for birth weight due to negative selection of severely discordant MZ twins. Furthermore, we test the hypothesis that MZ twins are less discordant for birth weight when comparing a volunteer based twin registry with a population based twin registry, due to selective registration. Data were available on 3927 twin pairs from the volunteer Australian Twin Registry born before 1964, 3059 volunteer twin pairs from the Netherlands Twin Register born 1987-1989 and 454 Belgian twin pairs from The East Flanders Prospective Twin Survey born 1987-1989. Intrapair relative birth weight differences (RBWD) were computed for MZ and dizygotic (DZ) twins from each twin registry. Comparing birth weight differences between MZ and DZ twins provides support for the hypothesis that MZ twins are subject to a negative selection in historical databases. Furthermore, Australian MZ twins have a lower RBWD compared to Dutch MZ twins when corrected for the RBWD of Australian and Dutch DZ twins, indicating circumstances which only affect MZ twins. Our hypothesis that MZ twins are less discordant for birth weight in a volunteer based twin registry compared to a population based twin registry had to be rejected. We suggest that investigators using historical databases to test the fetal origins hypothesis should be aware of this increased likelihood of selective exclusion of individuals with extreme morphometric parameters at time of birth.

Adolescent↗

Predictive value of basal follicle-stimulating hormone concentrations in a general subfertility population.

OBJECTIVE: To assess the predictive value of elevated basal FSH concentrations during the initial subfertility workup with respect to fecundity in a general subfertility population with ovulatory menstrual cycles. DESIGN: Nested case-control study. SETTING: Fertility center of a university hospital. PATIENT(S): Fifty subfertile women with basal FSH levels >10.0 IU/L and 50 age-matched controls. INTERVENTION(S): Long-term follow-up (3-7 years). MAIN OUTCOME MEASURE(S): Pregnancies, deliveries, and time to pregnancy. RESULT(S): Patients with elevated basal FSH levels and controls were comparable with regard to basic characteristics, clinical diagnoses, and subfertility treatment. Long-term follow-up showed that 52% of the women with elevated basal FSH concentrations became pregnant (positive predictive value 48%) versus 62% of the controls, and 42% versus 46% eventually delivered a child, respectively. The mean time to pregnancy was 3.0 years in the elevated-FSH group and 3.4 years in controls. Most of the pregnancies in both groups occurred after spontaneous conceptions. CONCLUSION(S): The results of this study suggest that screening for elevated basal FSH concentrations is of no additional value in a general subfertility population with ovulatory menstrual cycles.

Biomarkers↗

Measuring apoptosis in human spermatozoa: a biological assay for semen quality?

OBJECTIVE: [1] To determine whether apoptosis can be measured in ejaculated spermatozoa by flow cytometry using the Annexin V assay, which measures expression of phosphatidylserine on the outer leaflet of the cell membrane, or the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP [deoxy-uridine triphosphate] nick end labeling) assay, which measures occurrence of DNA strand breaks and [2] to correlate the outcome with routine semen variables and the hypoosmotic swelling (HOS) test. DESIGN: Pilot study and clinical trial. SETTING: Large teaching hospital and fertility center. PATIENT(S): Men whose semen was studied for various reasons. MAIN OUTCOME MEASURE(S): Percentage of apoptotic spermatozoa by two different assays, percentage of necrotic spermatozoa, concentration and motility of spermatozoa, and outcome of the HOS test. RESULT(S): Apoptosis can be measured in spermatozoa by flow cytometry using the Annexin V assay and the TUNEL assay. Twenty percent of spermatozoa were apoptotic according to both assays. A significant inverse correlation was seen between phosphatidylserine expression (Annexin V assay) and sperm concentration (r = -0.389; P<.05) and motility (r = -0.289; P<.05). A highly significant inverse correlation was seen between DNA double-strand breaks (TUNEL assay) and sperm concentration (r = -0.629; P<.0001). CONCLUSION(S): Flow cytometry can easily and reliably detect phosphatidylserine expression on the outer leaflet of the cell membrane and DNA strand breaks, both of which are hallmarks of apoptosis. About 20% of ejaculated spermatozoa are apoptotic, and the concentration of spermatozoa is lower in men with more apoptotic spermatozoa.

Annexin A5↗

Birth weight and age at menopause in Australian female twin pairs: exploration of the fetal origin hypothesis.

In a twin sample where duration of gestation can be controlled, a specific example of the fetal origins hypothesis concerning association between low birth weight and early age at menopause is explored. The hypothesis is based on the physiologically plausible path from intrauterine growth retardation and reduced numbers of primary follicles to an earlier menopause. The sample comprised 323 Australian female twin pairs where both co-twins had reached menopause naturally and reported on their weight at birth. Regression analysis showed no linear association between the two variables (P = 0.371, r(2) = 0.0009). Intra-pair differences in age at menopause were investigated in the context of relative birth weight of co-twins. In 265 pairs an intra-pair birth weight difference was reported. In monozygotic (MZ) pairs (n = 168) this allowed for control of genetic effects as well as gestation duration. No significant differences dependent on birth weight relative to co-twin were found for age at natural menopause in either MZ or dizygotic (DZ) twin pairs, even in pairs whose birth weights differed markedly. There was some indication that twins with premature ovarian failure were heavier at birth than twins with normal or later menopausal age. We conclude that the hypothesis that lower birth weight is associated with earlier menopause is not supported by our data.

Adult↗

Dose-finding study of triptorelin acetate for prevention of a premature LH surge in IVF: a prospective, randomized, double-blind, placebo-controlled study.

Gonadotrophin-releasing hormone agonists (GnRHa) are routinely used in IVF programmes to prevent an unwanted LH surge and consequent ovulation. Despite its widespread use in IVF, a convincing dose recommendation for GnRHa in IVF does not exist. In our opinion, the lowest possible dose of GnRHa should be used. Thus, we performed a prospective, randomized, double-blind, placebo-controlled study to determine the minimal daily dose of triptorelin acetate needed to suppress a premature LH surge during IVF treatment in a long protocol. A total of 240 women (60 in each group) was randomized to either placebo or to one of three doses of triptorelin, i.e. 15, 50 or 100 microg daily. Ovarian stimulation was performed with two or three ampoules of FSH daily. A premature LH surge occurred in 23% of placebo-treated patients, but in none of the triptorelin acetate-treated patients. There were significantly more oocytes and embryos in the 50 and 100 microg triptorelin groups. There was no dose relationship in rates of either implantation, pregnancy, ongoing pregnancy, live birth or baby take-home. In this study we showed that daily administration of 15 microg triptorelin is sufficient to prevent a premature LH surge, and that 50 microg is equivalent to 100 microg in terms of IVF results.

Cell Count↗

In-vitro fertilization in a spontaneous cycle: easy, cheap and realistic.

The results of in-vitro fertilization in natural cycles (NIVF) in women with tubal infertility at our department are presented. The study had a prospective design. We needed 75 cycles in 50 patients to obtain one oocyte from each patient. Successful oocyte recovery rate was 67% per started cycle and 82% per oocyte retrieval. Thirty-five embryos were transferred and resulted in four ongoing pregnancies (5.3% per cycle, 6.5% per oocyte retrieval, 11.4% per embryo transfer and 11.4% per embryo). Six patients who participated in the study made a second attempt at NIVF. Five of them conceived of which four were ongoing. Cumulative ongoing pregnancy rates are 9. 8% per cycle, 11.9% per oocyte retrieval, 19.5% per embryo transfer and 19.5% per embryo. We conclude that NIVF is an easy, cheap and realistic method to obtain a pregnancy for patients with tubal infertility.

Adult↗

Elevated FSH concentrations in imminent ovarian failure are associated with higher FSH and LH pulse amplitude and response to GnRH.

Imminent ovarian failure (IOF) in women is characterized by regular menstrual cycles and elevated early follicular phase FSH. This study explored underlying neuroendocrine causes of elevated FSH concentrations on day 3 of the menstrual cycle. The characteristics of episodic secretion of FSH and LH, the pituitary response to gonadotrophin-releasing hormone (GnRH), plasma oestradiol, and dimeric inhibin A and inhibin B on day 3 were compared in 13 women with elevated FSH concentrations (>10 IU/l) and 16 controls. FSH amplitudes were higher in the IOF group than in the controls (P < 0. 0001). The FSH pulse frequency did not differ between groups. The FSH response to GnRH was higher in the IOF patients than in the controls (P < 0.0001). Mean LH, LH amplitude and LH response to GnRH were higher in the IOF group, but LH pulse frequency did not differ between the groups. Concentrations of inhibin A and inhibin B were lower in the IOF group, while oestradiol showed no differences. We concluded that in women with IOF, the pituitary is more sensitive to GnRH. This leads to higher FSH and LH pulse amplitudes which underlie the elevated FSH concentrations in the early follicular phase.

Adult↗

Corticosteroids do not influence ovarian responsiveness to gonadotropins in patients with premature ovarian failure: a randomized, placebo-controlled trial.

OBJECTIVE: To determine the effect of corticosteroids on ovarian responsiveness to exogenous gonadotropins in patients with idiopathic premature ovarian failure (POF). DESIGN: Placebo-controlled, randomized, double-blind, multicenter study. SETTING: Two tertiary care academic centers for reproductive endocrinology and fertility and two general teaching hospitals. PATIENT(S): One hundred patients with idiopathic POF intended to enter the study. The study was discontinued after 36 patients failed to ovulate. INTERVENTION(S): Endocrine and immune parameters were tested on days 1 and 15. On day 1, subjects were randomized to receive either 9 mg of dexamethasone daily or placebo. From day 5 onward, 300 IU of hMG daily was added for 10 days in both groups. The dosage of dexamethasone was decreased stepwise in the second week and discontinued after day 15. Patients were monitored by transvaginal ultrasonography and by determining serum E2 levels. MAIN OUTCOME MEASURE(S): Ovulation rate. Fifty patients would have to be included in each study group to detect a statistically significant difference of 20% in the ovulation rate between the two groups with alpha = 0.05 and beta = 0.1 (one-tailed test). RESULT(S): No ovulation was recorded in the first 36 patients. Interim analysis showed that the 95% confidence intervals of an ovulation rate of 0 were 0-17% for the dexamethasone arm (n = 19) and 0-19% for the placebo arm (n = 17). Because the preset objective (a difference of 20%) would never be reached, the study was discontinued. CONCLUSION(S): Corticosteroids do not influence ovarian responsiveness to gonadotropins in patients with idiopathic POF.

Adrenal Cortex Hormones↗