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Biomedical subjects

Jolande A Land

Publications and source records attributed to Jolande A Land.

13 recordsLinked to original sources

Do host genetic traits in the bacterial sensing system play a role in the development of Chlamydia trachomatis-associated tubal pathology in subfertile women?

BACKGROUND: In women, Chlamydia (C.) trachomatis upper genital tract infection can cause distal tubal damage and occlusion, increasing the risk of tubal factor subfertility and ectopic pregnancy. Variations, like single nucleotide polymorphisms (SNPs), in immunologically important host genes are assumed to play a role in the course and outcome of a C. trachomatis infection. We studied whether genetic traits (carrying multiple SNPs in different genes) in the bacterial sensing system are associated with an aberrant immune response and subsequently with tubal pathology following a C. trachomatis infection. The genes studied all encode for pattern recognition receptors (PRRs) involved in sensing bacterial components. METHODS: Of 227 subfertile women, serum was available for C. trachomatis IgG antibody testing and genotyping (common versus rare allele) of the PRR genes TLR9, TLR4, CD14 and CARD15/NOD2. In all women, a laparoscopy was performed to assess the grade of tubal pathology. Tubal pathology was defined as extensive peri-adnexal adhesions and/or distal occlusion of at least one tube. RESULTS: Following a C. trachomatis infection (i.e. C. trachomatis IgG positive), subfertile women carrying two or more SNPs in C. trachomatis PRR genes were at increased risk of tubal pathology compared to women carrying less than two SNPs (73% vs 33% risk). The differences were not statistically significant (P = 0.15), but a trend was observed. CONCLUSION: Carrying multiple SNPs in C. trachomatis PRR genes tends to result in an aberrant immune response and a higher risk of tubal pathology following a C. trachomatis infection. Larger studies are needed to confirm our preliminary findings.

Antibodies, Bacterial↗

How should we report on perinatal outcome?

Authors should report on neonatal outcome after ART in a well-defined and uniform way, to enable readers to compare the outcome of different studies. For reporting on birthweight, SD scores (z-scores) are to be preferred, customized for the most important physiological variables affecting birthweight, e.g. gestational age, gender of the child and whether it is a singleton or part of a multiple. It may be suggested that ESHRE should support the construction of European customized birthweight tables and make available a software for calculating the z-scores in cohorts.

Birth Weight↗

Single versus double embryo transfer: cost-effectiveness analysis alongside a randomized clinical trial.

BACKGROUND: Twin pregnancies after IVF are still frequent and are considered high-risk pregnancies leading to high costs. Transferring one embryo can reduce the twin pregnancy rate. We compared cost-effectiveness of one fresh cycle elective single embryo transfer (eSET) versus one fresh cycle double embryo transfer (DET) in an unselected patient population. METHODS: Patients starting their first IVF cycle were randomized between eSET and DET. Societal costs per couple were determined empirically, from hormonal stimulation up to 42 weeks after embryo transfer. An incremental cost-effectiveness ratio (ICER) was calculated, representing additional costs per successful pregnancy. RESULTS: Successful pregnancy rates were 20.8% for eSET and 39.6% for DET. Societal costs per couple were significantly lower after eSET (7334 euro) compared with DET (10,924 euro). The ICER of DET compared with eSET was 19,096 euro, meaning that each additional successful pregnancy in the DET group will cost 19,096 euro extra. CONCLUSIONS: One cycle eSET was less expensive, but also less effective compared to one cycle DET. It depends on the society's willingness to pay for one extra successful pregnancy, whether one cycle DET is preferred from a cost-effectiveness point of view.

Adult↗

The CD14 functional gene polymorphism -260 C>T is not involved in either the susceptibility to Chlamydia trachomatis infection or the development of tubal pathology.

BACKGROUND: The functional polymorphism -260 C>T in the LPS sensing TLR4 co-receptor CD14 gene enhances the transcriptional activity and results in a higher CD14 receptor density. Individuals carrying the T/T genotype also have significantly higher serum levels of soluble CD14. The T allele of this polymorphism has recently been linked to Chlamydia pneumoniae infection. We investigated the role of the CD14 -260 C>T polymorphism in the susceptibility to and severity (defined as subfertility and/or tubal pathology) of C. trachomatis infection in Dutch Caucasian women. METHODS: The different CD14 -260 C>T genotypes were assessed by PCR-based RFLP analysis in three cohorts: 1) A cohort (n = 576) of women attending a STD clinic, 2) a cohort (n = 253) of women with subfertility, and 3) an ethnically matched control cohort (n = 170). The following variables were used in the analysis: In cohort 1 the CT-DNA status, CT IgG serology status, self-reported symptoms and in cohort 2, the CT IgG serology status and the tubal status at laparoscopy. RESULTS: In the control cohort the CC, CT and TT genotype distribution was: 28.2%, 48.2%, and 23.5% respectively. No differences were found in the overall prevalence of CD14 -260 genotypes (28.1%, 50.7%, and 21.2%) in cohort 1 when compared to the control cohort. Also no differences were observed in women with or without CT-DNA, with or without serological CT responses, with or without symptoms, or in combinations of these three variables. In subfertile women with tubal pathology (cohort 2, n = 50) the genotype distribution was 28.0%, 48.0%, and 24.0% and in subfertile women without tubal pathology (n = 203), 27.6%, 49.3% and 23.2%. The genotype distribution was unchanged when CT IgG status was introduced in the analyses. CONCLUSION: The CD14 -260 C>T genotype distributions were identical in all three cohorts, showing that this polymorphism is not involved in the susceptibility to or severity of sequelae of C. trachomatis infection.

Adolescent↗

In unselected patients, elective single embryo transfer prevents all multiples, but results in significantly lower pregnancy rates compared with double embryo transfer: a randomized controlled trial.

BACKGROUND: Elective single embryo transfer (eSET) in a selected group of patients (i.e. young patients with at least one good quality embryo) reduces the number of multiple pregnancies in an IVF programme. However, the reduced overall multiple pregnancy rate (PR) is still unacceptably high. Therefore, a randomized controlled trial (RCT) was conducted comparing eSET and double embryo transfer (DET) in an unselected group of patients (i.e. irrespective of the woman's age or embryo quality). METHODS: Consenting unselected patients were randomized between eSET (RCT-eSET) (n = 154) or DET (RCT-DET) (n = 154). Randomization was performed just prior to the first embryo transfer, provided that at least two 2PN zygotes were available. Non-participants received our standard transfer policy [SP-eSET in a selected group of patients (n = 100), otherwise SP-DET (n = 122)]. RESULTS: The ongoing PR after RCT-eSET was significantly lower as compared with RCT-DET (21.4 versus 40.3%) and the twin PR was reduced from 21.0% after RCT-DET to 0% after RCT-eSET. The ongoing PRs after SP-eSET and SP-DET did not differ significantly (33.0 versus 30.3%), with an overall twin PR of 12.9%. CONCLUSION: To avoid twin pregnancies resulting from an IVF treatment, eSET should be applied in all patients. The consequence would be a halving of the ongoing PR as compared with applying a DET policy in all patients. The transfer of one embryo in a selected group of good prognosis patients leads to a less drastic reduction in PR but maintains a twin PR of 12.9%.

Adult↗

Elective single embryo transfer (eSET) policy in the first three IVF/ICSI treatment cycles.

BACKGROUND: Elective single embryo transfer (eSET), applied in the first or second IVF cycle in young patients with good quality embryos, has been demonstrated to lower the twin pregnancy rate, while the overall pregnancy rate is not compromised. It is as yet unclear whether eSET could be the preferred transfer policy in all treatment cycles, or that it should be restricted to the first or first two cycles. METHODS: eSET policy (when two or more embryos were available, at least one of them being of good quality) was offered to patients younger than 38 years in the first three treatment cycles. Retrospectively, treatment cycle outcome was studied. RESULTS: In 326 patients, 586 treatment cycles were performed (326 first, 168 second and 92 third treatment cycles). In 65 cycles (11%), eSET could not be applied because there was either no fertilization, or only one embryo available. In the remaining 521 cycles, eSET was performed in 111 cycles (19%), while in 410 cycles, no good quality embryo was available resulting in the transfer of two embryos (double embryo transfer, DET). No significant differences in ongoing pregnancy rates after transfer of fresh embryos were observed between eSET and DET in the first (both 33%), second (36 and 23%, respectively) and third treatment cycles (20 and 24%, respectively). In significantly more eSET cycles compared to DET cycles, could embryos be frozen. This resulted in a significantly higher cumulative pregnancy rate after eSET compared to DET. CONCLUSIONS: In patients younger than 38 years with at least one top quality embryo, eSET can be the transfer policy of choice in at least the first three treatment cycles, since the pregnancy rates obtained in each treatment cycle are comparable to those after DET.

Adult↗

What is the most relevant standard of success in assisted reproduction? Defining outcome in ART: a Gordian knot of safety, efficacy and quality.

In the course of the present Debate series, several new outcome measures for assisted reproduction have been proposed to encourage the transfer of fewer embryos, in order to diminish the number of multiple pregnancies. The implementation of these recommendations, however, is hampered by the perception that safety and efficacy are communicating vessels: it is presumed that by decreasing the number of embryos transferred, pregnancy rates will decrease as well. Data from national and international registries, however, do not confirm the assumption of the communicating vessels: pregnancy rates tend to be low in countries in which many embryos are transferred, and the highest pregnancy rates occur where the number of embryos per transfer is low. Only top-level clinics (where treatment efficacy is guaranteed) are able to decrease the number of embryos transferred without compromising their pregnancy rate, and to vouch for safety in this way. Elective single embryo transfer (eSET) can never be mandatory in all patients, but the percentage of eSETs performed by a particular assisted reproduction treatment centre does reflect its quality: the ultimate outcome measure of efficacy ánd safety. Therefore, the eSET rate is the most relevant qualifier of performance in assisted reproduction.

Female↗

Evidence-based medicine for diagnostic questions.

When searching the medical care literature for evidence on a diagnostic test, three questions should be addressed each time a study is found: (1) Is this evidence about a diagnostic test valid? (2) Does the test accurately discriminate between patients who do and patients who do not have a specific disorder? (3) Can the test be applied to this patient who is right now sitting in front of me? We will discuss hysterosalpingography (HSG) as an example of a valid and accurate diagnostic test to be applied in a general population of subfertile couples to assess tubal patency (specificity 0.83). HSG is an unreliable test for diagnosing tubal occlusion however (sensitivity 0.65). If HSG were normal, other investigations could be pursued and diagnostic laparoscopy (LS) only performed if conception had not occurred by a later date. If HSG were abnormal, LS would be needed to confirm or exclude tubal occlusion. Patients with risk factors for pelvic or tubal disease, including an abnormal Chlamydia antibody test (CAT) and those showing abnormalities at pelvic examination, should proceed directly to LS because they are significantly more likely to have pelvic pathology. A completely different issue would be HSG as a prognostic test for the occurrence of pregnancy. In theory, the occurrence of pregnancy may be considered a gold standard; however, in reproductive medicine, with so many causes of subfertility other than tubal pathology, a diagnostic test for one single disorder, if normal, will never be able to accurately predict the eventual occurrence of pregnancy.

Adult↗

Interleukin-1B (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) gene polymorphisms are not associated with tubal pathology and Chlamydia trachomatis-related tubal factor subfertility.

BACKGROUND: Chlamydia trachomatis infections have been associated with tubal pathology. However, not all C.trachomatis-infected women actually develop tubal pathology. Recently, host genetic factors such as the interleukin-1 gene cluster have been linked to inflammatory and infectious diseases. METHODS: Dutch Caucasian women were investigated for (i) the role of interleukin-1B (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) gene polymorphisms in tubal pathology (group 1); and (ii) the presence of these gene polymorphisms in C.trachomatis IgG-positive women with and without tubal pathology (group 2). Group 1 consisted of women with (n = 40) or without (n = 95) tubal pathology, respectively, and group 2 of C.trachomatis IgG-positive women of whom 28 had tubal pathology at laparoscopy and 47 did not. IL-1B-511 and IL-1B+3954 gene polymorphisms were assessed by PCR-restriction fragment length polymorphism (RFLP), and the variable number of tandem repeats (VNTR) of the IL-1RN gene were assessed by a PCR-based assay. RESULTS: Neither IL-1B-511, IL-1B+3954 nor IL-1RN genotypes, allele or carrier frequencies showed significant association with tubal pathology or C.trachomatis post-infection-based tubal pathology. CONCLUSIONS: The data obtained suggest that specific IL-1 gene polymorphisms are not associated with the tubal pathology risk or to the development of C.trachomatis-based post-infectious severe sequelae.

Adult↗

Chromosomal region 11p15 is associated with male factor subfertility.

The molecular aetiology of male factor subfertility, due to impaired spermatogenesis, is still unknown in the majority of cases. It is thought to be a complex disorder in which multiple genes are implicated. Cryptorchidism and reduced fecundity are symptoms in male Beckwith-Wiedemann patients and the ZNF214 and ZNF215 genes, localized on chromosomal region 11p15, are associated with this syndrome. We hypothesized that the ZNF214 and ZNF215 genes, which are predominantly expressed in the testis, could be involved in male factor subfertility in patients with idiopathic impaired spermatogenesis or in patients with impaired spermatogenesis due to cryptorchidism. Male partners of subfertile couples with idiopathic azoo- or severe oligozoospermia, male partners with azoo- or severe oligozoospermia and cryptorchidism in their medical history and men with normozoospermia were screened for nine single nucleotide polymorphisms in the ZNF214 and ZNF215 genes. An association study was performed based on allele and estimated haplotype frequencies. Statistically significant differences in allele frequencies and in estimated haplotype frequencies were found in both patient groups compared with controls. Thereafter, both genes were screened for mutations in all patients by PCR and single strand conformation polymorphism analysis. Aberrant patterns were confirmed by DNA sequencing. Mutation analysis in ZNF214 and ZNF215 revealed five new variants in the patients that were not present in the controls. At least three of these mutations were inherited from the mother. Our results suggest that chromosomal region 11p15 is associated with male factor subfertility due to impaired spermatogenesis with and without cryptorchidism.

Case-Control Studies↗

Chlamydia infection and subfertility.

In the majority of women chlamydia infections remain asymptomatic but they may increase the risk for tubal factor subfertility. Pelvic inflammatory disease (PID) and its chronic sequelae are associated with chlamydial IgG antibody formation in serum, and a correlation between the height of antibody titres and the presence of tubal factor subfertility has been established. The predictive value of chlamydia antibody testing (CAT) is limited however. Several factors affecting sensitivity and specificity of CAT have been identified. Because it is assumed that the presence of chlamydial heat shock proteins (HSPs) may be indicative of chronic inflammation, chlamydial HSP60 antibody testing has been evaluated in its prediction of tubal factor subfertility.

Antibodies, Bacterial↗

Chlamydia trachomatis in subfertile women undergoing uterine instrumentation. Screen or treat?

Women who undergo uterine instrumentation are considered at risk for pelvic infections by Chlamydia trachomatis, which may derive either from ascending endocervical infections or from reactivation of micro-organisms persisting in the genital tract after previous chlamydia infections. Women presenting at fertility clinics frequently undergo uterine instrumentation (e.g. hysterosalpingography and laparoscopy with hydrotubation). Studies in subfertile women using DNA amplification techniques have shown that the prevalence of endocervical chlamydia infections is low (1.8%). In contrast, in 30-60% of subfertile women chlamydia IgG antibodies can be found in serum, indicating previous chlamydia infections. It has been demonstrated that, several years after chlamydia infections, viable micro-organisms may still be present in the upper genital tract. Therefore, subfertile women with chlamydia antibodies should be considered at risk for reactivation of persistent chlamydia infections after uterine instrumentation, even after exclusion of endocervical chlamydia infections. Moreover, in subfertile women without chlamydia antibodies, the presence of viable micro-organisms in the genital tract cannot be excluded. As a consequence, prophylactic antibiotics before uterine instrumentation should be considered in all subfertile women, instead of endocervical screening for C. trachomatis and treatment of positive cases only.

Antibiotic Prophylaxis↗

Chlamydia antibody testing in screening for tubal factor subfertility: the significance of IgG antibody decline over time.

BACKGROUND: Chlamydia (C.) trachomatis antibody testing in screening for tubal factor subfertility is limited by false negative results, i.e. negative Chlamydia antibody tests in patients with tubal pathology at laparoscopy. The present study was performed to determine whether decline in C. trachomatis IgG antibodies over time is responsible for those false negative results. METHODS: A total of 39 women with an initial titre of > or =64 were re-studied after 4-7 years. A new serum sample was collected from each patient. The initial and the second serum sample were tested for C. trachomatis IgG antibodies using a micro-immunofluorescence assay (MIF). A species-specific enzyme-linked immunosorbent assay (ELISA) was used to validate the MIF test results. All patients filled out a questionnaire to determine risk factors for renewed C. trachomatis infection between the initial and second serum sample. RESULTS: Seven of the 39 patients (18.0%) showed a decline (>2 titre steps) in IgG antibodies by MIF over a period of 4-7 years, but IgG antibodies never became undetectable. In the 7/39 patients who showed a decline by MIF, signal/cut-off values by ELISA did not change. CONCLUSION: A decline in IgG antibody titre is not a significant cause of false negative Chlamydia antibody test results.

Adult↗