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Biomedical subjects

J A M Kremer

Publications and source records attributed to J A M Kremer.

17 recordsLinked to original sources

Monitoring reproductive health in Europe: what are the best indicators of reproductive health? A need for evidence-based quality indicators of reproductive health care.

Monitoring reproductive health by the Reprostat indicators in Europe will facilitate the transparency of reproductive health as well as comparisons over time and between countries. However, for the monitoring and improvement of reproductive health care, we suggest the systematic development of evidence-based quality indicators, especially process and structure indicators.

Europe↗

A randomized clinical trial of clomiphene citrate versus low dose recombinant FSH for ovarian hyperstimulation in intrauterine insemination cycles for unexplained and male subfertility.

BACKGROUND: Controlled ovarian hyperstimulation with intrauterine insemination (IUI) is a widely accepted treatment for unexplained and male subfertility. No consensus exists about the drug of first choice to be used as hyperstimulation. This randomized multicentre trial using a parallel design compares the efficacy of clomiphene citrate (CC) with that of recombinant FSH (rFSH). METHODS: Couples with primary unexplained or male subfertility were randomized to receive CC or rFSH for ovarian hyperstimulation. The treatment was continued for up to four cycles unless pregnancy occurred. Cycles with more than three follicles were cancelled. Cumulative pregnancy rates and live birth rates were primary outcomes. Cancellation during treatment and multiple birth rates are secondary outcomes. Results were analysed following the intention-to-treat principle. RESULTS: Seventy couples with male subfertility and 68 couples with unexplained subfertility were included. Seventy-one women received CC, and 67 received rFSH. Twenty-seven pregnancies were observed in the CC group (38%) and 23 in the rFSH group (34.3%) relative risk (RR) 1.11 [95% confidence interval (95% CI) 0.71-1.73]. The live birth rate was 28.2% (20/71) and 26.9% (18/67) for CC and rFSH, respectively, RR 1.05 (95% CI 0.61-1.80). Overall, the live birth rates per cycle were 10% for CC-stimulated and 8.7% for rFSH stimulated cycles. The total multiple pregnancy rate was 6.0%. Thirty-five cycles (8.6%) were cancelled because of four or more follicles (CC, n = 17; rFSH, n = 18). CONCLUSIONS: In couples with primary unexplained or male subfertility participating in an IUI program, ovarian hyperstimulation can be achieved by CC or rFSH. No significant difference in live birth rates between CC and rFSH was observed. Being less expensive, CC seems the more cost-effective drug and therefore, can be offered as drug of first choice.

Adult↗

Globozoospermia revisited.

Globozoospermia is a rare (incidence <0.1%) but severe disorder in male infertility. Total globozoospermia is diagnosed by the presence of 100% round-headed spermatozoa lacking an acrosome. It is still unclear whether patients whose ejaculate contains both normal and globozoospermic cells (partial globozoospermia) suffer from a variation of the same syndrome. Apart from the fact that affected males suffer from reduced fertility or even infertility, no other physical characteristics can be associated with the syndrome. ICSI is a treatment option for these patients, although low fertilization rates after ICSI show a reduced ability to activate the oocyte. In globozoospermic cells, the use of acrosome markers has demonstrated an absent or severely malformed acrosome. Chromatin compaction appears to be disturbed but is not consistently over- or undercondensed. In some cases, an increased number of cells with DNA fragmentation have been observed. The analysis of the cytogenetic composition revealed an increased aneuploidy rate in some cases. Nonetheless, no increased number of spontaneous abortions or congenital defects has been reported in pregnancies conceived after ICSI. The pathogenesis of globozoospermia most probably originates in spermiogenesis, more specifically in acrosome formation and sperm head elongation. In several knockout mouse models, a phenotype similar to that in humans was found. Together with the occurrence of affected siblings, these findings indicate a genetic origin, which makes globozoospermia a good candidate for genetic analysis. More research is needed to elucidate the pathogenesis of human globozoospermia to further understand globozoospermia as well as (abnormalities in) spermiogenesis and spermatogenesis in general.

Adult↗

Patient-centred care: using online personal medical records in IVF practice.

BACKGROUND: Generic patient-accessible medical records have shown promise in enhancing patient-centred care for patients with chronic diseases. We sought to design, implement and evaluate a patient-accessible medical record specifically for patients undergoing a course of assisted reproduction (IVF or ICSI). METHODS: The personal medical record (PMR) database was developed using three formative evaluation steps, and its user-experience was evaluated through a cross-sectional study. Fifty-four patient-couples receiving an IVF or ICSI treatment in our hospital were granted access to the PMR. Main outcomes concern the usage of the PMR, the perceived usefulness of its functions and user attitudes towards privacy and financial issues. RESULTS: The PMR consists of 15 major functions that can be classified into personal information, general information and communication functions. Fifty-three patient-couples accessed the website and 51 couples filled out the evaluation questionnaire. They rated most functions as useful and preferred personalized to general functions. The results also show that some functions require further development. Patients using the PMR have little concerns regarding privacy, and 76% are willing to pay for such a service in the future. CONCLUSIONS: The patients in this study frequently and intensively used the Internet-accessible PMR. This suggests that the PMR offers very useful functions from an IVF/ICSI patient's perspective.

Databases, Factual↗

Long-term psychological adjustment to IVF/ICSI treatment in women.

BACKGROUND: The aim of this study was to gain more insight into long-term psychological adjustment to IVF in women. METHODS: In a prospective cohort study, 298 women entering their first IVF treatment cycle (including ICSI) completed standardized psychological questionnaires before the start of the treatment, just after the last treatment cycle, and 6 months and 3-5 years after the last treatment cycle. The main outcome measures were state anxiety, depression and mode of adaptation to unsuccessful IVF. RESULTS: Anxiety and depression were found at follow-up to return to baseline levels following treatment not resulting in a live birth, after an initial increase during treatment. On the contrary, treatment resulting in a live birth was found to lead to a more positive long-term emotional status. Women who focused on new life goals as a mode of adaptation 3-5 years after IVF without a live birth showed lower levels of anxiety and depression compared with those who persisted in their attempts to get pregnant. CONCLUSIONS: Treatment that resulted in a live birth led to more positive emotional adjustment. In addition, most women who did not give birth to a child after treatment adjusted well psychologically. Positive adjustment was related to developing new life goals rather than persisting in attempts to get pregnant. Helping women to change life goals after abandoning treatment might have beneficial effects on the adaptation process.

Adult↗

Decreased ovarian reserve relates to pre-eclampsia in IVF/ICSI pregnancies.

BACKGROUND: Pre-eclampsia affects 2-10% of all pregnancies and is a major cause of maternal and fetal morbidity and mortality. As compared with the general population, IVF pregnancies are associated with a 2.7-fold risk of pre-eclampsia. An advanced age and associated subfertility in the IVF group reflects a general decrease in ovarian reserve, which itself has been linked to cardiovascular disease. We tested the hypothesis that decreased ovarian reserve is associated with pre-eclampsia as a vascular complication in IVF/ICSI pregnancies. METHODS: In this retrospective case-control study, 41 cases with a history of pre-eclampsia were compared to 82 matched controls without hypertension or (pre)eclampsia. All pregnancies were established after IVF or ICSI. Several indicators of ovarian reserve such as variables related to basal ovarian function and response to hyperstimulation were compared in both the groups by multivariate analysis. The condition of the neonates was evaluated as well. RESULTS: A higher amount of total administered FSH and FSH per day, together with a lower number of obtained oocytes during IVF treatment, were associated with an increased risk to pre-eclampsia in a subsequent pregnancy. The administered FSH per follicle and per obtained oocyte showed even stronger relationships, the latter having the best predictive value. Neonatal outcome was comparable between the groups. CONCLUSION: Diminished responsiveness of the ovaries to FSH stimulation in an IVF cycle, reflecting decreased ovarian reserve, is associated with an increased risk of developing pre-eclampsia in a subsequent pregnancy.

Adult↗

Women's emotional adjustment to IVF: a systematic review of 25 years of research.

This review provides an overview of how women adjust emotionally to the various phases of IVF treatment in terms of anxiety, depression or general distress before, during and after different treatment cycles. A systematic scrutiny of the literature yielded 706 articles that paid attention to emotional aspects of IVF treatment of which 27 investigated the women's emotional adjustment with standardized measures in relation to norm or control groups. Most studies involved concurrent comparisons between women in different treatment phases and different types of control groups. The findings indicated that women starting IVF were only slightly different emotionally from the norm groups. Unsuccessful treatment raised the women's levels of negative emotions, which continued after consecutive unsuccessful cycles. In general, most women proved to adjust well to unsuccessful IVF, although a considerable group showed subclinical emotional problems. When IVF resulted in pregnancy, the negative emotions disappeared, indicating that treatment-induced stress is considerably related to threats of failure. The concurrent research reviewed, should now be underpinned by longitudinal studies to provide more information about women's long-term emotional adjustment to unsuccessful IVF and about indicators of risk factors for problematic emotional adjustment after unsuccessful treatment, to foster focused psychological support for women at risk.

Anxiety↗

Abnormal cervical cytology in women eligible for IVF.

BACKGROUND: Chlamydia trachomatis is more prevalent in subfertile women than in the general population and is the leading cause of tubal factor subfertility. As C. trachomatis infections are sexually transmitted, it can be expected that infections with human papillomavirus (HPV) are also more prevalent in this group of women. HPV is a necessary cause for the development of cervical (pre-)malignancies. We therefore hypothesized that subfertile women are more likely to have HPV-induced cervical abnormalities compared to the general population. METHODS: In this retrospective case-control study, all cervical smears of women visiting the fertility clinic for IVF (cases) and of women attending the population-based screening programme for cervical cancer (controls) were retrieved from an electronic database and assessed. RESULTS: The cases (n = 669) showed significantly more abnormal cervical smears compared to the controls (77,055) (6.1 and 3.9%, respectively, P < 0.02). CONCLUSIONS: The probability that subfertile women eligible for IVF are diagnosed with a high-grade cervical lesion is almost twice as high compared to women in the general population. We therefore suggest to take a cervical smear from all women referred for fertility problems.

Adult↗

Subfertility guidelines in Europe: the quantity and quality of intrauterine insemination guidelines.

BACKGROUND: International collaboration could facilitate systematic development of guidelines to regulate and improve clinical practice. To promote European collaboration in guideline development in reproductive medicine, insight into existing subfertility guidelines in Europe is essential. The study aim was to explore the number and quality of clinical practice guidelines on homologous intrauterine insemination (IUI) in Europe. METHODS: To identify IUI guidelines in Europe, electronic databases and Internet were systematically searched and key experts on assisted reproduction in 25 European countries were questioned. The quality of IUI guidelines was systematically assessed with the internationally validated Appraisal of Guidelines for Research and Evaluation (AGREE) Instrument. Qualitative methods were used to appraise IUI guideline recommendations and references. RESULTS: National guidelines on IUI are available in four of 25 European countries. The quality of IUI guidelines in Europe is moderate to high, but the recommendations and references differ considerably. CONCLUSIONS: The number of IUI guidelines in Europe is surprisingly small, and differences in their recommendations and references are considerable. To overcome these deficiencies in clinical guidance on IUI care in Europe, a central body with expertise in up-to-date guideline development methodology and sufficient resources could be established in Europe for central selection and international exchange of evidence to support guideline recommendations.

Europe↗

Heterogeneity in the origin of recurrent complete hydatidiform moles: not all women with multiple molar pregnancies have biparental moles.

Hydatidiform moles of two women, each with three molar pregnancies, were examined in order to study their origin. Multiple recurrences have previously been associated with women who have biparental complete hydatidiform moles (CHM). However, all the moles examined in this study were androgenetic CHM (AnCHM), indicating that recurrent (>2) moles, particularly in the absence of a positive family history, may be androgenetic rather than biparental. These data suggest that some women have a specific liability for having AnCHM. Making the distinction between a biparental or an androgenetic origin of recurrent moles is of relevance for counselling and when considering therapeutic options. Therefore, we propose that all recurrent moles should be investigated using molecular techniques.

Adult↗

Barriers to physician adherence to a subfertility guideline.

BACKGROUND: Guidelines aim to improve clinical practice but are not self-implementing. Insight into barriers to physician guideline adherence is crucial for development of effective implementation strategies. The study aim was to identify barriers to physician adherence to an intrauterine insemination (IUI) guideline of the Dutch Society of Obstetrics and Gynaecology. METHODS: We conducted a cross-sectional survey among all Dutch gynaecologists, residents and fertility physicians (n = 860), using written questionnaires that were based on information obtained in focus group discussions. We investigated barriers related to physicians' knowledge and attitudes, and external barriers. RESULTS: The response rate was 65%. We used 344 questionnaires for analysis. Physicians' knowledge was adequate, with a median unfamiliarity rate with each of the 31 key guideline recommendations of 12%. Physicians' attitudes were generally positive, especially regarding guideline development and quality. Important attitude-related barriers included physicians' lack of self-efficacy regarding physician-patient communication and poor outcome expectancy. External barriers were mostly related to specific patient characteristics and associated with higher age of physicians and fewer consultations for fertility problems per week. CONCLUSIONS: Multiple barriers impede physician adherence to subfertility guidelines, mainly physicians' lack of self-efficacy and low outcome expectancy. Both physicians and patients play an important role in future implementation interventions to optimize subfertility care.

Adult↗

A longitudinal, prospective study on emotional adjustment before, during and after consecutive fertility treatment cycles.

BACKGROUND: A longitudinal study into the course of the emotional response to IVF from pre-treatment to 6 months post-treatment and factors that contributed to that course. METHODS: A total of 148 IVF patients and 71 partners completed self-report questionnaires on anxiety, depression, personality characteristics, meaning of fertility problems, coping, marital relationship and social support at pre-treatment. Assessments of anxiety and depression were repeated immediately following the final treatment cycle and again 6 months later (follow-up). RESULTS: Women showed an increase of both anxiety and depression after unsuccessful treatment and a decrease after successful treatment. Men showed no change in anxiety and depression either after successful or after unsuccessful treatment. In the 6 months after unsuccessful treatment, women showed no recovery. At follow-up, >20% of the women showed subclinical forms of anxiety and/or depression. Personality characteristics, meaning of the fertility problems, and social support determined the course of the emotional response. CONCLUSIONS: Most women adjusted well to unsuccessful treatment, but at follow-up, a considerable proportion still showed substantial emotional problems. Personality characteristics, pre-treatment meaning of the fertility problems and social support have demonstrated the adjustment to unsuccessful IVF in women. This allows early identification of women at risk as well as tailored interventions.

Adaptation, Psychological↗

[Cryopreservation of semen of adolescents and young adult men with cancer].

The importance of cryopreserving semen for young male cancer patients is illustrated in three case descriptions. A 28-year-old man with chronic myeloid leukaemia that resulted in azoospermia, later fathered a child with his semen that had been stored prior to chemotherapy. In an 18-year-old adolescent with non-Hodgkin lymphoma the possibility to store cryopreserved semen was only raised after chemotherapy had been started and had caused azoospermia. This caused the patient serious regret. A 14-year-old boy with acute lymphatic leukaemia had his semen stored despite initial hesitations due to his young age. The cancer hardly ever affects the semen quality to the extent that cryopreservation of the semen becomes impossible. The aim should be to obtain several ejaculates prior to the cancer therapy and to store multiple portions, so that later a number of fertilisation attempts are possible. The primary attending physician is initially responsible for raising the possibility of semen cryopreservation. Ideally, however, all health professionals involved should be aware of this aspect. There is a need for multidisciplinary protocols for oncology centres and sperm banks, so that the timely informing of patients is guaranteed, responsibilities are recorded--with appropriate procedures to prevent unnecessary delay--and procedures that concur with legal requirements and financial constraints are established.

Adolescent↗

Current Internet use and preferences of IVF and ICSI patients.

BACKGROUND: Nowadays, the Internet has a tremendous impact on modern society, including healthcare practice. The study aim was to characterize current Internet use by IVF and ICSI patients and to identify their preferences regarding Internet applications in fertility care. METHODS: A total of 163 couples with fertility problems awaiting an IVF or ICSI procedure in the University Medical Centre Nijmegen, The Netherlands, was asked to complete a written questionnaire on Internet use in general, and also for fertility-related problems, preferences regarding Internet applications in fertility care and demographic characteristics. RESULTS: The response rate was 82%. In total, 81% of infertile couples used the Internet. Multivariate logistic regression analysis showed ethnic background and annual family income to be significant predictors of Internet use. Some 66% of Internet users and 54% of the total study population used the Internet for fertility-related problems. The female partners were the main Internet users with regard to fertility-related issues. In terms of preferences of the study participants, the majority favoured personal medical information online. CONCLUSIONS: Most infertile couples used the Internet with respect to fertility-related problems and were interested in implementation of Internet applications in fertility care. Healthcare providers should actively participate in the development and implementation of Internet applications in fertility care.

Adult↗

[Results of in vitro fertilization in the Netherlands, 1996-2000].

OBJECTIVE: To describe the annual results in all 13 Dutch in vitro fertilisation (IVF) centres in the period 1996-2000, and to look for possible differences between individual centres and years. DESIGN: Retrospective data collection, description and analysis. METHOD: The results collected on the website of the Dutch Society of Obstetrics and Gynaecology (Dutch acronym: NVOG; www.nvog.nl) in the period 1996-2000 were integrated and described, with special attention to possible differences between centres and years. RESULTS: In 1996-2000 (5 years), 63,414 IVF or ICSI treatment cycles were started in the Netherlands, and 5,884 transfers of cryopreserved embryos were performed. The number of treatment cycles increased over the years, particularly the number of ICSI cycles. The total number of ongoing pregnancies was 12,991 (20.5% per started cycle; 22.5% for ICSI and 18.3% for IVF). Particularly during the first 3 years, there was an increase in these percentages (IVF: from 16.4% (1996) to 19.2% (1998); ICSI: from 18.3% (1996) to 23.9% (1998)). There were differences between the centres in both the percentage of ongoing pregnancies per started IVF/ICSI cycle (range 13.7-25.1%) and the percentage ICSI (14-61%) and cryo-transfers per total number of treatment cycles (0-26%). It was estimated that, during this 5-year period, 1 out of every 61 Dutch neonates resulted from IVF or ICSI. CONCLUSION: The pregnancy-rates after IVF and ICSI increased during the study period, and were comparable with the rates in other European countries. Some important data are still missing from the inventory, for example regarding the number of embryos per transfer, multiple pregnancies, live births, congenital malformations and complications.

Embryo Transfer↗

[The emotional burden of artificial insemination: increased anxiety and depression following an unsuccessful treatment].

OBJECTIVE: Determination of the emotional burden of the first IVF or ICSI treatment cycle, the effect of the treatment on the marital relationship, and the course of the treatment following a failed and a successful first attempt. DESIGN: Descriptive longitudinal study with repeated measures before and after the first treatment cycle. METHOD: 240 women and 219 men filled in questionnaires both before and after the first treatment cycle in the area of anxiety, depression, and the marital relationship (as measured with the 'Spielberger state trait anxiety inventory' (STAI), the 'Beck depression inventory for primary care' (BDI-PC) and the 'Maudsley marital questionnaire' (MMQ), respectively), as well as their plans for further treatment. RESULTS: After a first failed treatment cycle, both women and men showed an increase in depression, while women also showed increased anxiety. No differences were found between pre- and post-treatment levels of anxiety and depression after a successful treatment. After the first failed cycle, almost 13% of the women showed clinically relevant forms of depression. There was an increase in dissatisfaction with the sexual relationship in both men and women regardless of the success of the treatment. Before the start of the first treatment cycle, 2% of the couples had no intention to undergo further treatment if the first cycle failed; none of these couples started a new cycle. Ultimately, 18% of the couples refrained from further treatment following a failed first treatment cycle. CONCLUSION: After a failed first treatment cycle the couples showed an increase in depression and one in eight women had a clinically relevant form of depression. More than one out of every 6 couples decided to refrain from further treatment after a failed first cycle.

Anxiety↗

No evidence for paternal mtDNA transmission to offspring or extra-embryonic tissues after ICSI.

There is a risk that ICSI may increase the transmission of mtDNA diseases to children born after this technique. Knowledge of the fate and transmission of paternal mitochondrial DNA is important since mutations in mitochondrial DNA have been described in oligozoospermic males. We have used an adaptation of solid phase mini-sequencing to exclude the presence of levels of paternal mtDNA >0.001% in ICSI families. This method is more sensitive than those used in previous studies and is sufficient to detect the likely paternal contribution (approximately 0.1-0.5% from simple calculations of expected dilution during fertilization). Using this method, we were able to detect concentrations as low as 0.001% paternal mtDNA in a maternal mtDNA background. No paternal mtDNA was detected in the embryonic (blood or buccal swabs) tissue of children born after ICSI nor in extra-embryonic tissue (placenta or umbilical cord). In conclusion, we did not detect paternal mtDNA in blood, buccal swabs, placenta or umbilical cord of children born after ICSI. We have found no evidence that ICSI increases the risk of paternal transmission of mtDNA and hence of mtDNA disorders.

DNA, Mitochondrial↗