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Biomedical subjects

F M Helmerhorst

Publications and source records attributed to F M Helmerhorst.

At least 73 records · Page 4Linked to original sources
PubMed1999

Venous thrombosis, oral contraceptives and high factor VIII levels.

Recently, it has been described that elevated plasma levels of factor VIII are a strong risk factor for venous thrombosis. We analysed the data of the Leiden Thrombophilia Study, a population based case-control study on the causes of venous thrombosis, to verify whether the risk due to oral contraceptive use was higher in women with higher factor VIII levels. Furthermore we investigated the joint risk of high factor VIII levels and oral contraceptive use. We selected 155 premenopausal women with deep-vein thrombosis and 169 control subjects, aged 15-49, who were at the time of their thrombosis (or similar date in control) not pregnant, nor in the puerperium, did not have a recent miscarriage, and were not using injectable progestogens. Of the patients, 109 (70%) women had used oral contraceptives during the month preceding their deep-vein thrombosis, in contrast to 65 (38%) of the control subjects (index date), yielding an odds ratio for oral contraceptive use of 3.8 (95% CI 2.4-6.0). Of the women who suffered a deep-vein thrombosis 56 (36%) had high factor VIII levels (> or =150 IU/dl) as compared with 29 (17%) of the control subjects, yielding an odds ratio for high factor VIII of 4.0 (95% CI 2.0-8.0), relative to factor VIII levels <100 IU/dl. The joint effect of oral contraceptive use and high factor VIII resulted in an odds ratio of 10.3 (95% CI 3.7-28.9), comparing women who had both with women who had neither. We conclude that there is an increase in risk due to oral contraceptive use in women with higher factor VIII levels and that both factors have additive effects.

Adolescent↗
PubMed1998

Effectiveness of the postcoital test: randomised controlled trial.

OBJECTIVES: To investigate the impact of the postcoital test on the pregnancy rate among subfertile couples and on the number of other diagnostic tests and treatments. DESIGN: Randomised controlled study. SETTING: A university and two non-university teaching hospitals in the Netherlands. SUBJECTS: New couples at infertility clinics, 1 March 1993 to 1 October 1995; randomisation to an intervention group (series of infertility investigations that include the postcoital test) or to a control group (series excluding the test). MAIN OUTCOME MEASURE: Cumulative pregnancy rate. RESULTS: Of 736 consecutive new couples, 444 fulfilled the inclusion criteria and consented to participate (intervention group, 227; control group, 217). Treatment was given more often in the intervention group than in the control group (54% v 41%; difference 13% (95% confidence interval 4% to 22%)). Yet cumulative pregnancy rates at 24 months in the intervention group (49% (42% to 55%)) and the control group (48% (42% to 55%)) were closely similar (difference 1% (-9.0% to 9.0%)). CONCLUSION: Routine use of the postcoital test in infertility investigations leads to more tests and treatments but has no significant effect on the pregnancy rate.

Adolescent↗
PubMed1998

Which prostanoid metabolites should be determined for the study of reproductive processes?

The non-enzymatic metabolites of prostacyclin (PGI2) and thromboxane A2 (TXA2), 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) and thromboxane B2 (TXB2), and their 2,3-dinor metabolites, 2,3-dinor-6-keto-PGF1alpha and 2,3-dinor-TXB2, were measured in early morning urine samples in 24 in vitro fertilization (IVF) cycles in 24 women and in 27 women who became pregnant after IVF and embryo transfer (ET). The sum of the non-enzymatic metabolites and their 2,3-dinor metabolites was considered to be a reflection of total PGI2 and total TXA2 production in vivo. Both the ratio of 'total' PGI2/'total' TXA2 and the ratio of the 2,3-dinor metabolites were calculated. TXB2 concentrations showed virtually no change and the ratios of the non-enzymatic metabolites of PGI2 and TXA2 versus their 2,3-dinor metabolites remained relatively constant. As a consequence, the ratio of 2,3-dinor-6-keto-PGF1alpha/2,3-dinor-TXB2 was a close reflection of the ratio of 'total' PGI2/'total' TXA2, although the latter ratio was significantly higher all the time. We conclude that for comparative studies on the balance between PGI2 and TXA2 in IVF cycles and during gestation, the determination of the 2,3-dinor metabolites alone can replace the measurement of all four metabolites.

Biomarkers↗
PubMed1998

Evaluation of pregnancy rates after intrauterine insemination according to indication, age, and sperm parameters.

PURPOSE: Our purpose was to evaluate intrauterine insemination results obtained in our clinic and identify prognostic factors for the chance of pregnancy. METHODS: A retrospective study of data from 1989 to 1996 was undertaken. Only first attempts were included in this study, except for the part on the cumulative pregnancy rates. Couples with either one-sided tubapathology, hormonal dysfunction, idiopathic infertility, or andrological indication were selected. All women were stimulated with clomiphene citrate. Five hundred sixty-six couples who underwent 1763 cycles were included in the study. RESULTS: The overall pregnancy rate for first pregnancies was 6.9% per cycle and 21.4% per patient. For first intrauterine insemination attempts this was 8.8% per cycle/patient, varying between 5.0% for andrological indication and 10.6% for tubapathology, 10.0% for idiopatic indication, and 10.3% for hormonal indication. These differences were not significant. Age did not have a significant effect either, although there were no pregnancies observed in women 40 years or older. The number of inseminated spermatozoa significantly affected the pregnancy rate: < 2 million, 4.6%; > or = 2 to < 10 million, 3.9%; and > or = 10 million, 11.3%. CONCLUSIONS: Unless semen characteristics are insufficient, intrauterine insemination is a useful treatment for infertile couples.

Adult↗
PubMed1998

Hemostatic effects of oral contraceptives in women who developed deep-vein thrombosis while using oral contraceptives.

OBJECTIVE: Comparison of the effect of oral contraceptives on hemostatic variables in venous thrombosis patients (thrombosis while using oral contraceptives) with the effect in healthy control subjects. Our aim was to assess whether some of these effects were more pronounced in women who had suffered thrombosis, i.e., whether these were "hemostatic hyperresponders". STUDY DESIGN: A population-based case-control study, the Leiden Thrombophilia Study. MATERIALS AND METHODS: We investigated 99 pre-menopausal women, age 15-49 years, who had used oral contraceptives at the time of a first, objectively confirmed episode of deep-vein thrombosis. They were not pregnant, nor in puerperium, nor had had a recent miscarriage, and were not using injectable progestogens, nor suffering from inherited coagulation defects. The median time between occurrence of deep-vein thrombosis and venepuncture was 18 months, and 30 of the 99 women were still using oral contraceptives, while 69 had discontinued oral contraceptive use. In addition, a group of 153 control women (54 of them were oral contraceptive users and 99 were non-users) were studied. The following hemostatic variables were measured: APTT, factor VII, factor VIII, factor XII, fibrinogen, prothrombin, total antithrombin, normalised activated protein C sensitivity ratio (n-APC-sr), protein C, protein S and free protein S. RESULTS: We found marked and significant effects of oral contraceptive use on the levels of several clotting factors, with an increase in factor VII, factor XII, protein C and a decrease in antithrombin, n-APC-sr and protein S. Less marked effects that were non-significant or only significant in either patients or controls, were an increase in factor VIII, fibrinogen and prothrombin and a decrease in the APTT and free protein S. In the former thrombosis patients several of these effects of oral contraceptives were more pronounced than in healthy women: specifically on factor VII, antithrombin, n-APC-sr and protein C. CONCLUSIONS: Our results of the effects of oral contraceptives generally confirm previous reports in healthy volunteers. Our data also show that in former deep-vein thrombosis patients these effects are more pronounced. Apparently some women become "high hemostatic responders" when exposed to oral contraceptives, and they may be the women most vulnerable to its thrombogenic effects.

Abortion, Spontaneous↗
PubMed1997

Third-generation oral contraceptive and deep venous thrombosis: from epidemiologic controversy to new insight in coagulation.

Four epidemiologic studies showed a twofold increase in risk of deep venous thrombosis with the use of oral contraceptives containing third-generation progestins, relative to second-generation products. These findings have been strongly debated ever since, and new studies have been added. In the current article we examine whether the findings can be explained by potential biases or other shortcomings of the epidemiologic studies. We conclude that complete certainty cannot exist but that the most rational conclusion from the epidemiologic findings and their discussion is that an increased risk of deep venous thrombosis with third-generation contraceptives is likely, especially in first-time and young users. The controversy has recently led to new insights in coagulation: Women who use third-generation contraceptives acquire a resistance to the blood's own anticoagulation system, similar to the activated protein C resistance that is seen in persons who carry the factor V Leiden mutation but different from that in women using second-generation contraceptives.

Bias↗
PubMed1997

Predicting optimal cervical mucus for infertility diagnosis.

OBJECTIVE: We studied the relationship between cervical mucus evaluations and daily fertility examinations in order to find monitoring techniques that can predict optimal mucus one day before it occurs. METHODS: Twenty-three healthy young female volunteers were followed during one spontaneous cycle with serial measurements of serum estradiol, progesterone, LH and FSH, urinary LH, and transvaginal ultrasound measurements of endometrial thickness and follicles. Data were related to cervical mucus scores. RESULTS: All cycles were ovulatory with optimal mucus, but in 14 optimal mucus was present for only one day. Echographic measurement of the leading follicle (mean diameter > or = 18 mm) could predict the day of optimal mucus in 78% and estradiol (> 700 pmol/l) in 83% of the cases. These two measurements combined predicted optimal mucus in 100% of the investigated women one day in advance. CONCLUSION: Optimal cervical mucus parameters can be predicted one day in advance by serial measurements of serum estradiol and follicular diameters.

Adolescent↗
PubMed1997

Oral contraceptives and thrombotic disease: risk of venous thromboembolism.

Studies conducted in the first three decades after discovery of a link between venous thromboembolism and oral contraceptive users showed a relative risk of first thrombosis during oral contraceptive use of 2.9 (95% CI 0.5-17). In recent studies in which the sub-50 micrograms ethinyl estrodiol containing pills were investigated comparing current users with non-users, the RR is 3.8 for non-fatal deep VTE and 2.7 for superficial VTE, deep VTE and pulmonary embolism (PE) together and 2.1 for fatal VT and PE together. The association is attributed to the estrogenic component and not related to duration of pill use. The risk disappears once the pill has been stopped, and it is not elevated among past users. Smoking does not appear to be risk factor for VTE; obesity and varicose veins are, at the most, weak risk factors. Since a causal relationship between OC use and VTE is tempting, clues for unraveling the mechanism were sought in the hemostatic system. Studies of the coagulation system found changes in the activation of coagulation and fibrinolytic compartments, but within the normal range. An epidemiologic study showed that the risk of VTE among women using OCs is 30-fold increased by the presence of a mutation of factor V, called Factor V Leiden (5% prevalence in the Caucasian population). Selective screening for the mutated factor V should be limited to women with a personal or family history of VTE. Four epidemiologic studies showed a two-fold increase in risk of VTE with the use of OCs containing third-generation progestins (gestodene and desogestrel), relative to second-generations products (levonorgestrel). Biases cannot devaluate the conclusion that the increased risk of VTE in especially first-time and younger users of third-generation OCs is highly likely. The clinical consequence is therefore that second-generation OCs are the first choice in prescription to first-time users.

Blood Coagulation↗
PubMed1996

Factor V Leiden: should we screen oral contraceptive users and pregnant women?

The factor V Leiden mutation is the most common genetic risk factor for deep vein thrombosis: it is present in about 5% of the white population. The risk of deep vein thrombosis among women who use oral contraceptives is greatly increased by the presence of the mutation. The same seems to be true of the risk of postpartum thrombosis. Several authors have called for all women to be screened before prescription of oral contraceptives and during pregnancy. Such a policy might deny effective contraception to a substantial number of women while preventing only a small number of deaths due to pulmonary emboli. Moreover, in pregnancy the ensuing use of oral anticoagulation prophylaxis might carry a penalty of fatal bleeding that is equal to or exceeds the risk of death due to postpartum thrombosis. It might pay, however, to take a personal and family history of deep vein thrombosis when prescribing oral contraceptives or at a first antenatal visit to detect women from families with a tendency to multiple thrombosis.

Contraceptives, Oral↗