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Biomedical subjects

F M Helmerhorst

Publications and source records attributed to F M Helmerhorst.

At least 19 recordsLinked to original sources
PubMed2006

Interleukin-10 promoter polymorphisms in male and female fertility and fecundity.

Interleukin-10 (IL10) is assumed beneficial for a successful pregnancy; it may increase fertility and fecundity. Allele frequencies of IL10 polymorphisms at position -2849, -1082 and -592 were analyzed in association with a past history of fertility and fecundity in men and women of at least 85 years old. Fertility was decreased in association with the -2849 A allele in females; 27% of the AA genotype carriers produced no offspring in marriage compared to 14% of the G allele carriers (odds ratio (OR): 2.2, 95% confidence interval (CI): 1.2-4.2, P=0.01). Effective fecundability was decreased in association with the -2849 A allele in females; 7% of female -2849 AA genotype carriers had a child within 371 days of marriage (therefore, conceived within 3 months of marriage) compared to 28% of female G allele carriers (OR: 0.2, 95% CI: 0.04-0.7, P=0.01). This suggests an association between the -2849 AA genotype and a decreased fertility and fecundity in females.

Aged, 80 and over↗
PubMed2006

Effects of urinary and recombinant gonadotrophins on gene expression profiles during the murine peri-implantation period.

BACKGROUND: Controlled ovarian stimulation (COS) with urinary gonadotrophins but not recombinant gonadotrophins, adversely affect the implantation process. In this study, we investigated the effects of urinary and recombinant gonadotrophins on gene expression profiles at implantation sites during the mouse peri-implantation period and the possible molecular mechanisms involved in the detrimental effects of urinary gonadotrophins using microarray technology. METHODS: Adult female CD1 mice were treated with (i) urinary human FSH (hFSH) and urinary HCG, (ii) recombinant hFSH and recombinant human LH or (iii) saline. Gene expression profiling with GeneChip mouse genome 430 2.0 arrays, containing 45 101 probe sets, was performed using implantation sites on embryonic day 5. Data were statistically analysed using Significance Analysis of Microarrays. Ten genes from the microarray analysis were selected for validation using quantitative RT-PCR (qRT-PCR). A parallel group of pregnant mice was allowed to give birth to study the effect of gonadotrophins on resorption. RESULTS: Urinary gonadotrophins differentially up-regulated the expression of 30 genes, increased resorption and reduced litter size, whereas recombinant gonadotrophins did not. Nine of the 10 genes were confirmed by qRT-PCR. CONCLUSIONS: Urinary gonadotrophins, but not recombinant gonadotrophins, exerted differential effects on gene expression during the murine peri-implantation period. These findings might contribute to improve protocols for COS, leading to higher successful pregnancy rates.

Animals↗
PubMed2006

Does subfertility explain the risk of poor perinatal outcome after IVF and ovarian hyperstimulation?

BACKGROUND: The primary objective of this study was to investigate whether subfertility explains poor perinatal outcome after assisted conception. A secondary objective was to test the hypothesis that ovarian hyperstimulation rather than the IVF procedure may influence the perinatal outcome. METHODS: Using data from a Dutch population-based historical cohort of women treated for subfertility, we compared perinatal outcome of singletons conceived after controlled ovarian hyperstimulation (COHS) and IVF (IVF + COHS; n = 2239) with perinatal outcome in subfertile women who conceived spontaneously (subfertile controls; n = 6343) and in women who only received COHS (COHS only; n = 84). Furthermore, we compared perinatal outcome of singletons conceived after the transfer of thawed embryos with (Stim + Cryo; n = 66) and without COHS (Stim - Cryo; n = 73). RESULTS: The odds ratios (ORs) for very low birthweight (<1500 g) and low birthweight (1500-2500 g) were 2.8 [95% confidence interval (95% CI) 1.9-3.9] and 1.6 (95% CI 1.2-1.8) in the IVF + COHS group compared with the subfertile control group. The ORs for very preterm birth (<32 weeks) and for preterm birth (32-37 weeks) were 2.0 (95% CI 1.4-2.9) and 1.5 (95% CI 1.3-1.8), respectively. Adjustment for confounders did not materially change these risk estimates. The difference in risk between the COHS-only group and the subfertile group was significant only for very low birthweight (OR 3.5; 95% CI 1.1-11.4), but the association became weaker after adjustment for maternal age and primiparity (OR 3.1; 95% CI 1.0-10.4). No significant difference in birthweight and preterm delivery was found between the group of children conceived after ovarian stimulation/ovulation induction and (Stim + Cryo) and the group of children conceived after embryo transfer of thawed embryos in a spontaneous cycle without ovarian stimulation/ovulation induction (Stim - Cryo). CONCLUSIONS: The poor perinatal outcome in this database could not be explained by subfertility and suggests that other factors may be important in the known association between assisted conception and poor perinatal outcome.

Adult↗
PubMed2006

Biphasic versus monophasic oral contraceptives for contraception.

BACKGROUND: Side effects caused by oral contraceptives discourage compliance with, and continuation of, oral contraceptives. Three approaches have been used to decrease these adverse effects: reduction of steroid dose, development of new steroids, and new formulas and schedules of administration. The third strategy led to the biphasic oral contraceptive pill. OBJECTIVES: To compare biphasic with monophasic oral contraceptives in terms of efficacy, cycle control, and discontinuation due to side effects. Our a priori hypotheses were: (a) biphasic oral contraceptives are less effective than monophasic oral contraceptives in preventing pregnancy; (b) biphasic oral contraceptives cause more side effects, give poorer cycle control, and have lower continuation rates. SEARCH STRATEGY: We searched the computerized databases MEDLINE, EMBASE, POPLINE, LILACS and CENTRAL. In addition, we searched the reference lists of all potentially relevant articles and book chapters. We also contacted the authors of relevant studies and pharmaceutical companies in Europe and the USA. SELECTION CRITERIA: We included randomized controlled trials comparing any biphasic with any monophasic oral contraceptive when used to prevent pregnancy. DATA COLLECTION AND ANALYSIS: We examined the studies found during the various literature searches for possible inclusion and assessed their methodology using Cochrane guidelines. We contacted the authors of all included studies and possibly randomized studies for supplemental information about methodology and outcome. We entered the data into RevMan, and calculated Peto odds ratios for the incidence of intermenstrual bleeding, absence of withdrawal bleeding, and study discontinuation due to intermenstrual bleeding. MAIN RESULTS: Only one trial of limited quality compared a biphasic and monophasic preparation. Percival-Smith 1990 examined 533 user cycles of a biphasic pill (500 microg norethindrone/35 microg ethinyl estradiol for 10 days, followed by 1000 microg norethindrone/35 microg ethinyl estradiol for 11 days; Ortho 10/11) and 481 user cycles of a monophasic contraceptive pill (1500 microg norethindrone acetate/30 microg ethinyl estradiol daily; Loestrin). The study found no significant differences in intermenstrual bleeding, amenorrhea and study discontinuation due to intermenstrual bleeding between the biphasic and monophasic oral contraceptive pills. AUTHORS' CONCLUSIONS: Conclusions are limited by the identification of only one trial, the methodological shortcomings of that trial, and the absence of data on accidental pregnancies. However, the trial found no important differences in bleeding patterns between the biphasic and monophasic preparations studied. Since no clear rationale exists for biphasic pills and since extensive evidence is available for monophasic pills, the latter are preferred.

Chemistry, Pharmaceutical↗
PubMed2006

Biphasic versus triphasic oral contraceptives for contraception.

BACKGROUND: Side effects caused by oral contraceptives discourage compliance with, and continuation of, oral contraceptives. A suggested disadvantage of biphasic compared to triphasic oral contraceptive pills is an increase in breakthrough bleeding. We conducted this systematic review to examine this potential disadvantage. OBJECTIVES: To compare biphasic with triphasic oral contraceptives in terms of efficacy, cycle control, and discontinuation due to side effects. SEARCH STRATEGY: We searched MEDLINE, EMBASE, POPLINE, LILACS and CENTRAL. We searched the reference lists of relevant articles and book chapters. We also contacted the authors of relevant studies and pharmaceutical companies in Europe and the USA. SELECTION CRITERIA: We included randomized controlled trials comparing any biphasic with any triphasic oral contraceptive when used to prevent pregnancy. DATA COLLECTION AND ANALYSIS: We examined the studies found during the searches for possible inclusion and assessed methodological quality using Cochrane guidelines. We contacted the authors of included studies and of possibly randomized studies for supplemental information about the methods and outcomes. We entered the data into RevMan. We calculated Peto odds ratios for incidence of discontinuation due to medical reasons, intermenstrual bleeding, and absence of withdrawal bleeding. MAIN RESULTS: Only two trials of limited quality met our inclusion criteria. Larranaga 1978 compared two biphasic pills and one triphasic pill, each containing levonorgestrel and ethinyl estradiol. No important differences emerged, and the frequency of discontinuation due to medical problems was similar with all three pills. Percival-Smith 1990 compared a biphasic pill containing norethindrone (Ortho 10/11) with a triphasic pill containing levonorgestrel (Triphasil) and with another triphasic containing norethindrone (Ortho 7/7/7). The biphasic pill had inferior cycle control compared with the levonorgestrel triphasic. The odds ratio of cycles with intermenstrual bleeding was 1.7 (95% CI 1.3 to 2.2) for the biphasic compared with the triphasic levonorgestrel pill. The odds ratio of cycles without withdrawal bleeding was 6.5 (95% CI 3.1 to 13). In contrast, cycle control with the biphasic pill was comparable to that of the triphasic containing the same progestin (norethindrone). AUTHORS' CONCLUSIONS: The available evidence is limited and the internal validity of these trials is questionable. Given the high losses to follow up, these reports may even be considered observational. Given that caveat, the biphasic pill containing norethindrone was associated with inferior cycle control compared with the triphasic pill containing levonorgestrel. The choice of progestin may be more important than the phasic regimen in determining bleeding patterns.

Contraception↗
PubMed2006

Triphasic versus monophasic oral contraceptives for contraception.

BACKGROUND: Side effects of oral contraceptive pills (OCs) discourage adherence to and continuation of OC regimens. Strategies to decrease adverse effects led to the introduction of the triphasic OC in the 1980s. Whether triphasic OCs have higher accidental pregnancy rates than monophasic pills is unknown. Nor is it known if triphasic pills give better cycle control and fewer side effects than the monophasic pills. OBJECTIVES: To compare triphasic OCs with monophasic OCs in terms of efficacy, cycle control, and discontinuation due to side effects. SEARCH STRATEGY: We searched the computerized databases of MEDLINE, EMBASE, POPLINE, LILACS and CENTRAL. Additionally, we searched the reference lists of relevant articles and book chapters. We also contacted researchers and pharmaceutical companies in Europe and the U.S. to identify other trials not found in our search. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing any triphasic OC with any monophasic pill used to prevent pregnancy. Interventions had to include at least three treatment cycles. DATA COLLECTION AND ANALYSIS: We assessed the studies found in the literature searches for possible inclusion and for their methodological quality. We contacted the authors of all included studies and of possibly randomized trials for supplemental information about the methods and outcomes studied. We entered the data into RevMan 4.2 and calculated odds ratios for the outcome measures of efficacy, breakthrough bleeding, spotting, withdrawal bleeding and discontinuation. MAIN RESULTS: Of 21 trials included, 18 examined contraceptive effectiveness: the triphasic and monophasic preparations did not differ significantly. Several trials reported favorable bleeding patterns, i.e. less spotting, breakthrough bleeding or amenorrhea, in triphasic versus monophasic OC users. However, meta-analysis was generally not possible due to differences in measuring and reporting the cycle disturbance data as well as differences in progestogen type and hormone dosages. No significant differences were found in the numbers of women who discontinued due to medical reasons, cycle disturbances, intermenstrual bleeding or adverse events. AUTHORS' CONCLUSIONS: The available evidence is insufficient to determine whether triphasic OCs differ from monophasic OCs in effectiveness, bleeding patterns or discontinuation rates. Therefore, we recommend monophasic pills as a first choice for women starting OC use. Large, high-quality RCTs that compare triphasic and monophasic OCs with identical progestogens are needed to determine whether triphasic pills differ from monophasic OCs. Future studies should follow the WHO recommendations on recording menstrual bleeding patterns and the CONSORT reporting guidelines.

Contraception↗
PubMed2006

Copper containing, framed intra-uterine devices for contraception.

BACKGROUND: Intrauterine devices (IUD) are safe and effective methods of long term reversible contraception. Design and copper content of IUDs could affect their effectiveness and side-effect profile. OBJECTIVES: We compared different copper IUDs for their effectiveness and side effects. SEARCH STRATEGY: Multiple electronic databases were searched with appropriate key words and names of the IUDs known to be in the market. We searched the reference lists of papers identified and contacted trialists when possible. SELECTION CRITERIA: Randomised controlled trials comparing different IUDs were considered. Trials needed to report on clinical outcomes. DATA COLLECTION AND ANALYSIS: Data on outcomes and trial characteristics were extracted in duplicate and independently by two reviewers. Meta-analysis results are expressed as rate difference (RD) using a fixed-effects model with 95% confidence interval (CI). In the presence of significant heterogeneity a random-effects model was applied. MAIN RESULTS: We included 34 trials, resulting in 16 comparisons of different IUDs. TCu380A was more effective than MLCu375, MLCu250, TCu220 and TCu200. Changing the position of the copper on the arm of the IUD for TCu380S did not improve the efficacy of TCu380A. MLCu375 was no more effective than TCu220, at 1 year, MLCu250 to 3 years or NovaT to 3 years Compared to TCu380A, none of the IUDs showed any benefits in terms of bleeding or pain, or any of the other reasons for early discontinuation. AUTHORS' CONCLUSIONS: TCu380A is more effective compared to other IUDs. There is no data available comparing different IUDs in special subgroups, such as nulliparous women.

Contraception↗
PubMed2006

Routine use of hysterosalpingography prior to laparoscopy in the fertility workup: a multicentre randomized controlled trial.

BACKGROUND: A multicentre randomized controlled trial with or without hysterosalpingography (HSG) was conducted to assess the usefulness of HSG as a routine investigation in the fertility workup prior to laparoscopy and dye. METHODS: From 1 April 1997 to 1 April 2002, subfertile women were allocated by a computer-based 1 : 1 ratio randomization procedure, either for an HSG followed by laparoscopy and dye (the intervention group) of for laparoscopy and dye only (the control group) as a part of their fertility workup. Cumulative pregnancy rate (CPR) within 18 months after randomization was the primary outcome of interest. RESULTS: 344 women were randomized to the intervention group (n = 169) and the control group (n = 175). There was no significant difference in CPR at 18 months in the intervention group (49.1%) [95% confidence interval (CI) 41.6 to 56.6] and the control group (50.3%) (95% CI 42.8 to 57.8), a difference of -1.2% (95% CI -11.8% to 9.5%). CONCLUSION: The routine use of HSG at an early stage in the fertility workup prior to laparoscopy and dye does not influence CPR, compared with the routine use of laparoscopy and dye without HSG.

Adult↗
PubMed2006

Gender-specific association of the factor V Leiden mutation with fertility and fecundity in a historic cohort. The Leiden 85-Plus Study.

BACKGROUND: Factor V Leiden (FVL, Arg506Gln) mutation may facilitate embryo implantation and increase fertility and fecundity. This was studied in subjects who were of childbearing age in a time with minimal fertility control without modern contraceptive methods. METHODS: From 1986 to 1999, 1502 inhabitants of Leiden, The Netherlands, reaching the age of 85 years were enrolled in the Leiden 85-Plus Study. Of 1176 subjects the FVL status was analysed, in 365 male and 811 female subjects. RESULTS: The FVL carrier rate was 4.3%. Fertility was not affected by FVL status. In male subjects, fecundity (interval between marriage and birth of first child) was significantly increased in FVL carriers; 67% of male FVL carriers had a child within 371 days of marriage (therefore conceived within 3 months of marriage), compared with 19% of male non-carriers [relative risk (RR), 3.5; 95% confidence interval (CI), 2.1-5.7; P < 0.001]. Within 6 months of marriage, 75% of male FVL carriers had conceived a child compared with 34% male non-carriers (RR, 2.2; 95% CI, 1.5-3.2; P = 0.01). In female subjects, fecundity was not influenced by FVL status. CONCLUSION: Fecundity is increased in male FVL carriers; in female subjects, no such association was observed.

Aged, 80 and over↗
PubMed2006

Combination contraceptives: effects on weight.

BACKGROUND: Weight gain is often considered a side effect of combination hormonal contraceptives, and many women and clinicians believe that an association exists. Concern about weight gain can limit the use of this highly effective method of contraception by deterring the initiation of its use and causing early discontinuation among users. However, a causal relationship between combination contraceptives and weight gain has not been established. OBJECTIVES: The aim of the review was to evaluate the potential association between combination contraceptive use and changes in weight. SEARCH STRATEGY: We searched the computerized databases MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS for studies of combination contraceptives. We also wrote to known investigators and manufacturers to request information about other published or unpublished trials not discovered in our search. SELECTION CRITERIA: All English-language, randomized controlled trials were eligible if they had at least three treatment cycles and compared a combination contraceptive to a placebo or to a combination contraceptive that differed in drug, dosage, regimen, and/or study length. DATA COLLECTION AND ANALYSIS: All titles and abstracts located in the literature searches were assessed. Data were entered and analyzed with RevMan, and a second author verified the data entered. Depending on the data available, the weighted mean difference using a fixed effects model with 95% confidence intervals (CI) was calculated for the mean change in weight between baseline and post-treatment measurements or the Peto odds ratio with 95% confidence intervals was calculated using the proportion of women who gained or lost more than a specified amount of weight. MAIN RESULTS: The three placebo-controlled, randomized trials did not find evidence supporting a causal association between combination oral contraceptives or a combination skin patch and weight gain. Most comparisons of different combination contraceptives showed no substantial difference in weight. In addition, discontinuation of combination contraceptives because of weight gain did not differ between groups where this was studied. AUTHORS' CONCLUSIONS: Available evidence was insufficient to determine the effect of combination contraceptives on weight, but no large effect was evident.

Body Weight↗
PubMed2006

Cluster headache in women: relation with menstruation, use of oral contraceptives, pregnancy, and menopause.

In contrast with migraine, little is known about the relation between cluster headache and menstrual cycle, oral contraceptives, pregnancy, and menopause. A population based questionnaire study was performed among 224 female cluster headache patients, and the possible effect of hormonal influences on cluster headache attacks studied. For control data, a similar but adjusted questionnaire was sent to healthy volunteers and migraine patients. It was found that menstruation, use of oral contraceptives, pregnancy, and menopause had a much smaller influence on cluster headache attacks than in migraine. Cluster headache can, however, have a large impact on individual women, for example to refrain from having children.

Adult↗
PubMed2005

Intra-uterine insemination versus timed intercourse for cervical hostility in subfertile couples.

BACKGROUND: The postcoital test has poor diagnostic and prognostic characteristics. Nevertheless, some physicians believe it can identify scanty or abnormal mucus that might impair fertility. One way to avoid 'hostile' cervical mucus is intrauterine insemination. With this technique, the physician injects sperm directly into the uterine cavity through a small catheter passed through the cervix; the theory is to bypass the "hostile" cervical mucus. Although most gynaecological societies do not endorse use of intrauterine insemination for hostile cervical mucus, some physicians consider it an effective treatment for women with infertility thought due to cervical mucus problems. OBJECTIVES: The aim of this review was to determine the effectiveness of intrauterine insemination with or without ovarian stimulation in women with cervical hostility who failed to conceive. SEARCH STRATEGY: We searched Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library Issue 2, 2005, MEDLINE (1966 to June 2005), EMBASE (1980 to June 2005), POPLINE (to June 2005) and LILACS (to June 2005). In addition, we contacted experts and searched the reference list of relevant articles and book chapters. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials comparing intrauterine insemination with intercourse timed at the presumed fertile period. Participants were women with cervical hostility who failed to conceive for at least one year. DATA COLLECTION AND ANALYSIS: We assessed the titles and abstracts of 386 publications and two reviewers independently abstracted data on methods and results from five studies identified for inclusion. The main outcome is pregnancy rate per couple. MAIN RESULTS: We did not pool the outcomes of the included five studies in a meta-analysis due to the methodological quality of the trials and variations in the patient characteristics and interventions. Narrative summaries of the outcomes are provided. Each study was too small for a clinically relevant conclusion. None of the studies provided information on important outcomes such as spontaneous abortion, multiple pregnancies, and ovarian hyperstimulation syndrome. AUTHORS' CONCLUSIONS: There is no evidence from the published studies that intrauterine insemination is an effective treatment for cervical hostility. Given the poor diagnostic and prognostic properties of the postcoital test and the observation that the test has no benefit on pregnancy rates, intrauterine insemination (with or without ovarian stimulation) is unlikely to be a useful treatment for putative problems identified by postcoital testing.

Biomarkers↗
PubMed2005

Anonymous or identity-registered sperm donors? A study of Dutch recipients' choices.

BACKGROUND: The aim of the present study was to gain insight into parents' own donor preferences within a system offering the choice between an anonymous and identity-registered donor. A comparison was made between recipients choosing for an anonymous donor (AD choosers) and those choosing for an identifiable donor (ID choosers) with regard to their sexual orientation, demographic characteristics, disclosure issues and infertility distress. METHODS: Data from 105 couples (61% heterosexual, 39% lesbian) were registered on a standardized form during implication counselling sessions previous to treatment. RESULTS: Sixty-three per cent of the heterosexual couples and 98% of the lesbian couples had chosen an ID donor. Major differences between ID and AD choosers were identified. Among the ID choosers secrecy towards the child was no option, whereas 83% of the AD choosers did not intend to inform their child. Compared with heterosexual ID choosers, AD choosers were more distressed about their infertility and had a lower educational level. CONCLUSION: Legislation imposing ID donors appears to be acceptable for the majority of this study population. For a vulnerable group of heterosexual couples, who remained secretive about the use of a donor, adaptation to the new system is not self-evident.

Choice Behavior↗
PubMed2004

Factor V Leiden mutation in relation to fecundity and miscarriage in women with venous thrombosis.

BACKGROUND: Factor V Leiden mutation (Arg506Gln) increases the likelihood of venous thrombosis; it may also have a positive effect through facilitation of embryo implantation. This may manifest itself as a reduced time to pregnancy (increased fecundity) and fewer miscarriages in the first trimester. METHODS: From March 1999 onwards, consecutive patients with a first venous thrombosis (VT) were recruited. The first 115 female VT patients with factor V Leiden and 230 age-matched female VT patients without factor V Leiden were included. All patients, unaware of their genotype, received a structured questionnaire. RESULTS: Of the 297 (86%) women who returned the questionnaire, 220 had been pregnant at least once. Time to first pregnancy was unaffected by carrier status: 58% factor V Leiden carriers reported a pregnancy within 3 months compared to 54% non-carriers. The miscarriage proportion was 14%, similar in both groups. First trimester miscarriage was less frequent among carriers (46%) than among non-carriers (95%) (relative risk 0.5, 95% confidence interval 0.3-0.9). CONCLUSIONS: Factor V Leiden mutation may support embryo implantation, as factor V Leiden carriers had fewer miscarriages in the first trimester with a similar overall miscarriage rate. Miscarriage of embryos with poor viability may be postponed until the second trimester in factor V Leiden carriers. Fecundity was not influenced by factor V Leiden status.

Abortion, Spontaneous↗
PubMed2004

Urinary gonadotrophins but not recombinant gonadotrophins reduce expression of VEGF120 and its receptors flt-1 and flk-1 in the mouse uterus during the peri-implantation period.

BACKGROUND: Ovarian stimulation in humans might affect the perinatal outcome and be considered as a stress factor in the implantation process. In this study we compared the effects of recombinant and urinary gonadotrophins during the mouse peri-implantation period. METHODS: Adult female CD1 mice were treated as follows (a) urinary hFSH and urinary hCG, (b) recombinant hFSH and recombinant hLH and (c) saline. The effects of the gonadotrophins on the expression of vascular endothelial growth factor120 (VEG120) and its receptors and the corticotrophin releasing hormone (CRH) system during the peri-implantation period were studied. The specific effects of the different gonadotrophins on the onset of implantation were also studied. RESULTS: Urinary gonadotrophin treatment caused lower levels of VEGF120, flt-1 and flk-1 mRNA levels, reduced the size of the embryo implantation site, delayed implantation and prolonged the gestational period. Both urinary hFSH and urinary hCG contributed to the adverse effects. Levels of CRH and CRHR1 expression were not influenced. Recombinant gonadotrophin treatment did not alter any of the parameters studied. CONCLUSIONS: Our results show that the VEGF system of the mouse uterus during the peri-implantation period is adversely affected by urinary gonadotrophins but not by recombinant gonadotrophins. The CRH system was not affected by the two types of gonadotrophins.

Animals↗
PubMed2004

Progestogens in combined oral contraceptives for contraception.

BACKGROUND: The progestogen component of oral contraceptives (OC) has undergone changes since it was first recognised that their chemical structures could influence the spectrum of minor adverse and beneficial effects. The major determinants of OCs are effectiveness, cycle control and common side effects. The rationale of this review is to provide a systematic comparison of OCs containing the progestogens currently in use worldwide. OBJECTIVES: The objective of this review is to compare currently available low-dose OCs containing ethinyl estradiol and different progestogens in terms of contraceptive effectiveness, cycle control, side effects and continuation rates. SEARCH STRATEGY: The Cochrane Controlled Trials Register, MEDLINE and EMBASE databases have been searched systematically. Relevant pharmaceutical companies and the authors of articles included in this review have been contacted for clarification. SELECTION CRITERIA: Randomised trials reporting clinical outcomes were considered for inclusion. We excluded studies comparing mono- with multiphasic pills, and crossover trials with trials in which the difference in total content of ethinyl estradiol between preparations exceeded 105 micro g. DATA COLLECTION AND ANALYSIS: The methodological quality and validity of studies were assessed based on the above-mentioned inclusion criteria. Both application of inclusion criteria and data extraction were performed independently by the reviewers. Results are expressed as relative risk (RR) with 95% confidence interval (CI) using a random-effects model. MAIN RESULTS: Twenty-two trials have been included in this review, thus generating 14 comparisons. Eighteen trials were sponsored by pharmaceutical companies and in only 5 cases had a blind trial been attempted. Most comparisons between different interventions included 1-3 trials. There was less discontinuation with second- compared to first-generation progestogens (RR: 0.79, 95% CI: 0.69-0.91). Cycle control appears to be better when using second- compared to first-generation progestogens for both mono- (RR: 0.69; 95% CI: 0.52-0.91) and triphasic (RR: 0.61; 95% CI: 0.43-0.85) preparations.Contraceptive effectiveness, spotting, breakthrough bleeding and the absence of withdrawal bleeding was similar when using GSD compared to LNG, although there was less intermenstrual bleeding in the GSD group (RR: 0.71, 95% CI: 0.55, 0.91). Drospirenone (DRSP) appeared to be similar to DSG. REVIEWERS' CONCLUSIONS: Based on data from one trial, compared to pills containing LNG, those containing GSD may be associated with less intermenstrual bleeding although they show similar patterns of spotting, breakthrough bleeding and the absence of withdrawal bleeds. GSD is also comparable to DSG. Regarding acceptability, all the indices show that third- and second-generation progestogens are preferred over first-generation preparations. Future research should focus on independently conducted, well-designed randomised trials that compare third- and second-generation progestogens in particular.

Contraception↗
PubMed2004

Interleukin 10-2849AA genotype protects against pre-eclampsia.

Recently, it has been described that human fertility is associated with the interleukin 10 (IL10) -2849 AA genotype. Pre-eclampsia is the most common pregnancy-specific complication. In the pathogenesis of pre-eclampsia, IL10 may affect maternal intravascular inflammation as well as endothelial dysfunction. Therefore, we tested the hypothesis that pre-eclampsia is associated with genetic variation in the IL10 promoter region in a case-control study for pre-eclampsia. Women homozygous for the IL10 -2849A allele have a threefold reduced risk for pre-eclampsia compared to controls (odds ratio 0.29; 95% CI 0.10-0.83). No differences in genotype frequency were found for polymorphisms in the IL10 promoter region at positions -1082, -819 and -592. This suggests that there is a genetically determined mechanism which protects the mother against pre-eclampsia, as reflected in the lower frequency of the IL10 -2849AA genotype in pre-eclamptic women.

Case-Control Studies↗