Maas Jan Heineman

Gender Difference in the Non‐Specific and Specific Immune Response in Humans

Problem:  The purpose of this present ex vivo study is to get insight in the sex differences of the basic non‐specific and specific immune response.

Chromosomal mosaicism in human preimplantation embryos: a systematic review

BACKGROUND Although chromosomal mosaicism in human preimplantation embryos has been described for almost two decades, its exact prevalence is still unknown. The prevalence of mosaicism is important in the context of preimplantation genetic screening in which the chromosomal status of an embryo is determined by the analysis of a single cell from that embryo. METHODS Here we report a systematic review and meta-analysis of studies on the chromosomal constitution of human preimplantation embryos. In 36 studies, out of 2117 citations that met our search criteria, data were provided extensively enough to allow classification of each analysed embryo with prespecified criteria for its chromosomal makeup. The main outcome of this classification was the prevalence of chromosomal mosaicism in human preimplantation embryos. RESULTS A total of 815 embryos could be classified. Of these, 177 (22%) were diploid, 599 (73%) were mosaic, of which 480 (59% of the total number of embryos) were diploid-aneuploid mosaic and 119 (14% of the total number of embryos) were aneuploid mosaic, and 39 (5%) contained other numerical chromosomal abnormalities. The distribution of the embryos over these categories was associated with the developmental stage of the embryos, the method used for analysis and the number of chromosomes analysed. CONCLUSIONS Diploid-aneuploid mosaicism is by far the most common chromosomal constitution in spare human preimplantation embryos after IVF. This undermines the reliable determination of the ploidy status of a cleavage-stage embryo based on the analysis of a single cell. Future research should determine the origin and developmental potential of mosaic embryos.

The immune response during the luteal phase of the ovarian cycle: increasing sensitivity of human monocytes to endotoxin

OBJECTIVE To test the hypothesis that during the luteal phase of the human ovarian cycle, as compared with the follicular phase, the percentage of cytokines producing peripheral monocytes after in vitro stimulation with endotoxin is increased. DESIGN Prospective study. SETTING Academic research institution. PATIENT(S) Women with regular menstrual cycles. INTERVENTION(S) Blood samples were collected between days 6 and 9 of the menstrual cycle (follicular phase) and between days 6 and 9 of the menstrual cycle following the LH surge (luteal phase). MAIN OUTCOME MEASURE(S) Percentages of tumor necrosis factor (TNF)-alpha-, interleukin (IL)-1 beta-, and IL-12-producing monocytes as well as total white blood cell (WBC) count, differential WBC counts, and plasma 17 beta-estradiol and progesterone concentrations. RESULT(S) Mean plasma 17 beta-estradiol and progesterone concentrations, percentage of TNF-alpha- and IL-1 beta-producing monocytes, WBC counts, and granulocyte cell count were significantly increased in the luteal phase as compared with the follicular phase of the ovarian cycle. The percentage of IL-12-producing monocytes, monocyte count and lymphocyte count did not vary between the 2 phases of the ovarian cycle. CONCLUSION(S) Together with an increase in progesterone and 17 beta-estradiol during the luteal phase, there is an increase in percentage TNF-alpha- and IL-1 beta-producing peripheral monocytes after in vitro stimulation with endotoxin as compared with the follicular phase of the ovarian cycle. Whether this increased sensitivity of monocytes for proinflammatory stimuli during the luteal phase is due to increased plasma levels of progesterone or 17 beta-estradiol needs further investigation.

No beneficial effect of preimplantation genetic screening in women of advanced maternal age with a high risk for embryonic aneuploidy

BACKGROUND Human preimplantation embryos generated through in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatments show a variable rate of numerical chromosome abnormalities or aneuploidies. Preimplantation genetic screening (PGS) has been designed to screen for aneuploidies in high risk patients, with the aim of improving live birth rates in IVF/ICSI. We assessed whether the effect of PGS on live births rates differs in women of advanced maternal age with variable risks for embryonic aneuploidy, and weighed these effects against the results obtained after IVF/ICSI without PGS. METHODS The effect of PGS on live birth rates was compared between groups defined by maternal age, number of previous miscarriages, semen quality, total amount of recombinant FSH (rFSH) administered during ovarian stimulation and total number of top-quality embryos, using data from a randomized controlled trial among women of advanced maternal age (35-41 years). RESULTS There was no significant differential effect of PGS in groups based on maternal age (P-value of interaction 0.16), the number of previous miscarriages (P-value of interaction 0.93), semen quality (P-value of interaction 0.26), rFSH dose (P-value of interaction 0.15) or the number of top-quality embryos (P-value of interaction 0.59). Live birth rates after IVF/ICSI with PGS were lower in all groups when compared with live birth rates after IVF/ICSI without PGS. CONCLUSIONS The paradigm that the effect of PGS is determined by a womans risk for embryonic aneuploidy seems incorrect. In fact, PGS has no clinical benefit over standard IVF/ICSI in women of advanced maternal age regardless of their risk for embryonic aneuploidy.

A Systematic Review of the Impact of Physicians’ Occupational Well-Being on the Quality of Patient Care

BackgroundIt is widely held that the occupational well-being of physicians may affect the quality of their patient care. Yet, there is still no comprehensive synthesis of the evidence on this connection.PurposeThis systematic review studied the effect of physicians’ occupational well-being on the quality of patient care.MethodsWe systematically searched PubMed, Embase, and PsychINFO from inception until August 2014. Two authors independently reviewed the studies. Empirical studies that explored the association between physicians’ occupational well-being and patient care quality were considered eligible. Data were systematically extracted on study design, participants, measurements, and findings. The Medical Education Research Study Quality Instrument (MERSQI) was used to assess study quality.ResultsUltimately, 18 studies were included. Most studies employed an observational design and were of average quality. Most studies reported positive associations of occupational well-being with patient satisfaction, patient adherence to treatment, and interpersonal aspects of patient care. Studies reported conflicting findings for occupational well-being in relation to technical aspects of patient care. One study found no association between occupational well-being and patient health outcomes.ConclusionsThe association between physicians’ occupational well-being and health care’s ultimate goal—improved patient health—remains understudied. Nonetheless, research up till date indicated that physicians’ occupational well-being can contribute to better patient satisfaction and interpersonal aspects of care. These insights may help in shaping the policies on physicians’ well-being and quality of care.

The Effect of Testosterone on Cytokine Production in the Specific and Non-specific Immune Response

Problem:  Cytokine production of monocytes and lymphocytes differs between males and females. This difference is characterized by a decreased percentage of interleukin (IL)‐2‐producing lymphocytes and an increased percentage of IL‐12, IL‐1β and tumour necrosis factor (TNF)‐α‐producing monocytes in males compared with females. In the present study, we investigated whether testosterone may explain these differences.

Good Clinical Teachers Likely to be Specialist Role Models: Results from a Multicenter Cross-Sectional Survey

Context Medical educational reform includes enhancing role modelling of clinical teachers. This requires faculty being aware of their role model status and performance. We developed the System for Evaluation of Teaching Qualities (SETQ) to generate individualized feedback on previously defined teaching qualities and role model status for faculty in (non) academic hospitals. Objectives (i) To examine whether teaching qualities of faculty were associated with their being seen as a specialist role model by residents, and (ii) to investigate whether those associations differed across residency years and specialties. Methods & Materials Cross-sectional questionnaire survey amongst 549 Residents of 36 teaching programs in 15 hospitals in the Netherlands. The main outcome measure was faculty being seen as specialist role models by residents. Statistical analyses included (i) Pearsons correlation coefficients and (ii) multivariable logistic generalized estimating equations to assess the (adjusted) associations between each of five teaching qualities and ‘being seen as a role model’. Results 407 residents completed a total of 4123 evaluations of 662 faculty. All teaching qualities were positively correlated with ‘being seen as a role model’ with correlation coefficients ranging from 0.49 for ‘evaluation of residents’ to 0.64 for ‘learning climate’ (P<0.001). Faculty most likely to be seen as good role models were those rated highly on ‘feedback’ (odds ratio 2.91, 95% CI: 2.41–3.51), ‘a professional attitude towards residents’ (OR 2.70, 95% CI: 2.34–3.10) and ‘creating a positive learning climate’ (OR 2.45, 95% CI: 1.97–3.04). Results did not seem to vary much across residency years. The relative strength of associations between teaching qualities and being seen as a role model were more distinct when comparing specialties. Conclusions Good clinical educators are more likely to be seen as specialist role models for most residents.

Cytokine Production by Monocytes, NK Cells, and Lymphocytes Is Different in Preeclamptic Patients as Compared with Normal Pregnant Women

Objective. To measure cytokine production in ex vivo stimulated leukocyte populations of women with normal pregnancy and those with preeclampsia. Methods. Whole blood from preeclamptic and normal pregnant women was stimulated with LPS or PMA/Ca-ionophore. The percentages of IFNγ and IL-2, 4, and 10 producing lymphocytes and NK cells and the percentages of TNFα, IL-1β, and IL-12 producing monocytes were measured by flowcytometry. Results. In women with preeclampsia, there was a significantly increased percentage IL-4 producing cytotoxic T cells. Also, a significant decreased percentage IL-2 producing T helper cells and IL-12 producing monocytes was seen as compared with normal pregnancy. Conclusion. Th1 cytokine production of lymphocytes and monocytes appears to be decreased in our group of preeclamptic patients compared with normal pregnant women.

The predictive value of ovarian reserve tests for spontaneous pregnancy in subfertile ovulatory women

BACKGROUND The predictive value of ovarian reserve tests (ORTs) for spontaneous pregnancy is unclear. Our study aimed to determine whether ORTs have added value to previously identified prognostic factors for spontaneous pregnancy in subfertile ovulatory couples. METHODS A prospective cohort study was performed on 474 subfertile ovulatory couples in two hospitals in Groningen, The Netherlands. The ORTs performed were: antral follicle count (AFC), follicle-stimulating hormone (FSH), inhibin B (basal levels and after stimulation with clomiphene citrate) and the clomiphene citrate challenge test. For each couple, the probability of spontaneous pregnancy was retrospectively calculated using the validated Hunault prediction model which includes the main known prognostic factors for spontaneous pregnancy. Outcome measure was time to spontaneous pregnancy resulting in a live birth. RESULTS When added to the Hunault model, only basal FSH and AFC significantly improved the prediction of spontaneous pregnancy (P-values of 0.05 and 0.04). Absolute changes in predicted probabilities after adding basal FSH or AFC were small: the predicted probability of spontaneous pregnancy shifted >or=10% in only 3.8% and 7.9% of the couples, respectively. CONCLUSIONS Although basal FSH and AFC significantly improved the validated prediction model for spontaneous pregnancy, the clinical relevance of this finding is limited. We recommend that none of the ORTs studied should be used routinely in the subfertility evaluation of ovulatory couples to predict spontaneous pregnancy chances.

Feedback or biofeedback to augment pelvic floor muscle training for urinary incontinence in women: Shortened version of a Cochrane systematic review

Feedback and biofeedback (BF) are common adjuncts to pelvic floor muscle training (PFMT) for women with stress, urgency, and mixed urinary incontinence (UI). An up to date systematic review of adjunctive feedback or BF was needed to guide practice and further research.