Great expectations of IVF patients: the role of gender, dispositional optimism and shared IVF prognoses.

STUDY QUESTION: Which success rates do female and male IVF patients expect, what determines their expectations and do patients reconsider their expectations after receiving a personal IVF prognosis at the expense of anxious reactions? SUMMARY ANSWER: Female and male IVF patients have unrealistic high expectations which are positively associated with their dispositional optimism, and which are only reconsidered by patients receiving a less than average IVF prognosis, which leads to more anxious reactions in females. WHAT IS KNOWN ALREADY: Female patients undergoing IVF are known to have unrealistic expectations of the success of their own IVF cycle. The available evidence suggests women expect above average performance of their fertility clinic and (family) reproductive systems. The association of gender and personality trait dispositional optimism, with expectations of IVF success and the impact of providing couples with their IVF prognosis have not been studied previously. STUDY DESIGN, SIZE, DURATION: A total of 148 partnered individuals participated in this prospective survey at two separate points in treatment: following oocyte aspiration (T1) and embryo transfer (T2) (2019-2020, participation rate = 85%). At the time of embryo transfer, gynaecologists provided couples with their IVF prognosis, calculated with the Adapted van Loendersloot model. Women and their male partners completed questionnaires independently and immediately following oocyte aspiration and embryo transfer. PARTICIPANTS/MATERIALS, SETTING, METHODS: Dispositional optimism ('LOT-R' questionnaire) and expectations of IVF success (numerical rating scale) were assessed in eligible couples commencing a 2nd-6th IVF cycle on T1. Expectations of IVF success and anxiety ('Spielberger State-Anxiety Inventory') were (re)assessed on T2. The inter-partner correlation of expectations of IVF success was examined. Linear mixed models examined hypothesized determinants of expectations of IVF success (T1) and explored (determinants of) whether participants reconsidered their expectations after receiving their IVF prognosis (T1-T2) and whether couple's IVF prognosis was associated with anxious reactions (T2). MAIN RESULTS AND THE ROLE OF CHANCE: The mean of the IVF success rates expected by patients immediately after oocyte aspiration was 59.1% (±20.0), irrespective of gender (P = 0.077). Partners expectations of IVF success were moderately correlated (r = 0.483; P < 0.001). Expectations of IVF success were positively associated with the participant's dispositional optimism (P < 0.001) but were not associated with their partner's dispositional optimism, women's age and their previous (un)successful IVF experiences. Gynaecologists gave couples their calculated IVF prognosis ranging from 4.8% to 69.2% (mean = 30.9%) at the time of embryo transfer. Gender did not influence whether participants reconsidered their expectations after receiving their prognosis. In contrast to the subgroup (n = 78), who received at least an average IVF prognosis and that did not reconsider their expectations of IVF success, the subgroup (n = 70) receiving a below average IVF prognosis lowered their expectations of IVF success (interaction effect: P < 0.001) from 55% to 46%. A below average IVF prognosis was associated with anxious reactions in women but not in men (interaction effect: P = 0.011). LIMITATIONS, REASONS FOR CAUTION: The study design and sample size were more optimal for examining hypothesized determinants of patient's expectations of IVF success than for studying the impact of sharing prognoses with patients. Whether (reconsidering) expectations influences IVF discontinuation rates and achieved live birth rates has yet to be followed-up. WIDER IMPLICATIONS OF THE FINDINGS: Clinics are advised to offer patients the opportunity of receiving their IVF prognosis. Providing prognoses is in line with patient preferences and tempers the unrealistic high expectations of both partners in couples with a less than average prognosis. A sensitive communication style is indicated, as lower prognoses are associated with mild anxious reactions in women. STUDY FUNDING/COMPETING INTEREST(S): E.A.F.D. holds a postdoctoral fellowship of the Research Foundation-Flanders (12H9819N) and this study was funded by the Research Council of the KU Leuven (C14/18/106; project of J.V., K.P. and E.A.F.D.) and as an investigator sponsored study of K.P. and E.A.F.D. by Merck nv/sa Belgium, an affiliate of Merck KGaA, Darmstadt, Germany. The authors declare no conflict of interest related to this study. TRIAL REGISTRATION NUMBER: N/A.

TRPV1 dysfunction in cystinosis patients harboring the homozygous 57 kb deletion.

Cystinosis is a rare autosomal recessive disorder characterized by lysosomal cystine accumulation due to loss of function of the lysosomal cystine transporter (CTNS). The most common mutation in cystinosis patients of Northern Europe consists of a 57-kb deletion. This deletion not only inactivates the CTNS gene but also extends into the non-coding region upstream of the start codon of the TRPV1 gene, encoding the capsaicin- and heat-sensitive ion channel TRPV1. To evaluate the consequences of the 57-kb deletion on functional TRPV1 expression, we compared thermal, mechanical and chemical sensitivity of cystinosis patients with matched healthy controls. Whereas patients heterozygous for the 57-kb deletion showed normal sensory responses, homozygous subjects exhibited a 60% reduction in vasodilation and pain evoked by capsaicin, as well as an increase in heat detection threshold. Responses to cold, mechanical stimuli or cinnamaldehyde, an agonist of the related nociceptor channel TRPA1, were unaltered. We conclude that cystinosis patients homozygous for the 57-kb deletion exhibit a strong reduction of TRPV1 function, leading to sensory deficiencies akin to the phenotype of TRPV1-deficient mice. These deficits may account for the reported sensory alterations and thermoregulatory deficits in these patients, and provide a paradigm for life-long TRPV1 deficiency in humans.

Psychometric functions for efficient and effective psychophysical testing of sensory function.

An efficient test for sensory function has been reported using random order pairs of real and sham stimuli. The constant magnitude of the real stimulus is chosen such that the first error in a patient's forced-choice report on the order of real and sham stimulation, immediately indicates abnormal sensory function. This magnitude just exceeds a critical large percentile of the psychometric function (i.e. the relationship between percentage of detection and stimulus magnitude in healthy subjects). The aim was to determine psychometric functions for one tongue site and six facial sites for adjusting three variants of the real/sham stimulus method (i.e. for light touch, cold sensation and for two-point discrimination). All 150 healthy subjects participated in testing for light touch sensation, 100 subjects additionally participated in testing two-point discrimination and 50 subjects participated additionally in testing cold sensation. The stimulus magnitude was varied using a staircase-limits procedure. Following curve fitting with a Boltzmann function, 90th, 95th or 99th percentiles of the psychometric functions were determined. A set of at least two real/sham tests, one testing the function of large nerve fibres and one for small fibres, allows quick assessment of a patient's disturbed sensory function including its fibre pathology.

Extension of normal values on sensory function for facial areas using clinical tests on touch and two-point discrimination.

The threshold value of a sensory test provides a numerical measure of the sensory function. In order to decide whether a threshold value from an affected site indicates 'abnormal' sensory function, it can be compared with normal values from a healthy control population. The aim of this study was to extend current information on normal values for static light touch and static two-point discrimination for facial sites. Using simple hand-held devices, 95% upper limits of confidence intervals of threshold values were determined for facial sites other than those studied previously and for a large sample of 100 healthy subjects. The MacKinnon-Dellon Disk-Criminator and the Aesthesiometer were used to measure novel normal values of two-point discrimination. As threshold values for two-point discrimination from the Aesthesiometer were similar to those obtained using the Disk-Criminator, the use of the Aesthesiometer might not be indicated. Apart from the Pressure Specified Sensory Device (a device with pressure control), Semmes-Weinstein nylon monofilaments and the Disk-Criminator are useful devices for studying sensory function, in particular under clinical test conditions in which easy and fast application are advantageous.

Role of caveolar compartmentation in endothelium-derived hyperpolarizing factor-mediated relaxation: Ca2+ signals and gap junction function are regulated by caveolin in endothelial cells.

BACKGROUND: In endothelial cells, caveolin-1, the structural protein of caveolae, acts as a scaffolding protein to cluster lipids and signaling molecules within caveolae and, in some instances, regulates the activity of proteins targeted to caveolae. Specifically, different putative mediators of the endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation are located in caveolae and/or regulated by the structural protein caveolin-1, such as potassium channels, calcium regulatory proteins, and connexin 43, a molecular component of gap junctions. METHODS AND RESULTS: Comparing relaxation in vessels from caveolin-1 knockout mice and their wild-type littermates, we observed a complete absence of EDHF-mediated vasodilation in isolated mesenteric arteries from caveolin-1 knockout mice. The absence of caveolin-1 is associated with an impairment of calcium homeostasis in endothelial cells, notably, a decreased activity of Ca2+-permeable TRPV4 cation channels that participate in nitric oxide- and EDHF-mediated relaxation. Moreover, morphological characterization of caveolin-1 knockout and wild-type arteries showed fewer gap junctions in vessels from knockout animals associated with a lower expression of connexins 37, 40, and 43 and altered myoendothelial communication. Finally, we showed that TRPV4 channels and connexins colocalize with caveolin-1 in the caveolar compartment of the plasma membrane. CONCLUSIONS: We demonstrated that expression of caveolin-1 is required for EDHF-related relaxation by modulating membrane location and activity of TRPV4 channels and connexins, which are both implicated at different steps in the EDHF-signaling pathway.

Testing of iatrogenic lingual nerve injury using a novel psychophysical method and oral reflexes.

In a case of long-term sensory loss in the tongue following third molar extraction, a novel, efficient and effective psychophysical test was used. This initial test, which includes the presentation of pairs of a real and fake stimulus, and a forced-choice response, was applied to determine whether relatively thick or thin afferent fibres of the lingual nerve were affected. The results suggested that thick fibres on the right tongue side were mainly affected. Sensory loss was confirmed and its extent assessed by a standard test determining thresholds of light touch. Furthermore, sensory function was determined by an objective test based on inhibitory reflexes in masseteric electromyographic activity following electrical stimulation of oral tissue. Reflex features that are important for within-patient diagnosis are a difference between the injured and control sides in latency of the first reflex, and also in depth-contrast in signal amplitude between both sides at the post-stimulus time of the trough of an inhibition on the uninjured side. In agreement with the findings from the psychophysical tests, the finding of the absence of an early component of both inhibitions suggested sensory loss related to dysfunction of fast-conducting, relatively thick afferent fibres of the lingual nerve. Apart from being used for medicolegal reasons, the objective reflex test may have conclusive prognostic value or may influence surgical therapeutic decisions.

A novel function of capsaicin-sensitive TRPV1 channels: involvement in cell migration.

Cell migration relies on a tight temporal and spatial regulation of the intracellular Ca2+ concentration ([Ca2+]i). [Ca2+]i in turn depends on Ca2+ influx via channels in the plasma membrane whose molecular nature is still largely unknown for migrating cells. A mechanosensitive component of the Ca2+ influx pathway was suggested. We show here that the capsaicin-sensitive transient receptor potential channel TRPV1, that plays an important role in pain transduction, is one of the Ca2+ influx channels involved in cell migration. Activating TRPV1 channels with capsaicin leads to an acceleration of human hepatoblastoma (HepG2) cells pretreated with hepatocyte growth factor (HGF). The speed rises by up to 50% and the displacement is doubled. Patch clamp experiments revealed the presence of capsaicin and resiniferatoxin (RTX)-sensitive currents. In contrast, HepG2 cells kept in the absence of HGF are not accelerated by capsaicin and express no capsaicin- or RTX-sensitive current. The TRPV1 antagonist capsazepine prevents the stimulation of migration and inhibits capsaicin-sensitive currents. Finally, we compared the contribution of capsaicin-sensitive TRPV1 channels to cell migration with that of mechanosensitive TRPV4 channels that are also expressed in HepG2 cells. A specific TRPV4 agonist, 4alpha-phorbol 12,13-didecanoate, does not increase the displacement. In summary, we assigned a novel role to capsaicin-sensitive TRPV1 channels. They are important Ca2+ influx channels required for cell migration.

Modulation of the Ca2 permeable cation channel TRPV4 by cytochrome P450 epoxygenases in vascular endothelium.

TRPV4 is a broadly expressed Ca2+-permeable cation channel in the vanilloid subfamily of transient receptor potential channels. TRPV4 gates in response to a large variety of stimuli, including cell swelling, warm temperatures, the synthetic phorbol ester 4alpha-phorbol 12,13-didecanoate (4alpha-PDD), and the endogenous lipid arachidonic acid (AA). Activation by cell swelling and AA requires cytochrome P450 (CYP) epoxygenase activity to convert AA to epoxyeicosatrienoic acids (EETs) such as 5,6-EET, 8,9-EET, which both act as direct TRPV4 agonists. To evaluate the role of TRPV4 and its modulation by the CYP pathway in vascular endothelial cells, we performed Ca2+ imaging and patch-clamp measurements on mouse aortic endothelial cells (MAECs) isolated from wild-type and TRPV4(-/-) mice. All TRPV4-activating stimuli induced robust Ca2+ responses in wild-type MAECs but not in MAECs isolated from TRPV4(-/-) mice. Upregulation of CYP2C expression by preincubation with nifedipine enhanced the responses to AA and cell swelling in wild-type MAECs, whereas responses to other stimuli remained unaffected. Conversely, inhibition of CYP2C9 activity with sulfaphenazole abolished the responses to AA and hypotonic solution (HTS). Moreover, suppression of EET hydrolysis using 1-adamantyl-3-cyclo-hexylurea or indomethacin, inhibitors of soluble epoxide hydrolases (sEHs), and cyclooxygenases, respectively, enhanced the TRPV4-dependent responses to AA, HTS, and EETs but not those to 4alpha-PDD or heat. Together, our data establish that CYP-derived EETs modulate the activity of TRPV4 channels in endothelial cells and shows the unraveling of novel modulatory pathways via CYP2C modulation and sEH inhibition.

Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4.

TRPV4 is a Ca(2+)- and Mg(2+)-permeable cation channel within the vanilloid receptor subgroup of the transient receptor potential (TRP) family, and it has been implicated in Ca(2+)-dependent signal transduction in several tissues, including brain and vascular endothelium. TRPV4-activating stimuli include osmotic cell swelling, heat, phorbol ester compounds, and 5',6'-epoxyeicosatrienoic acid, a cytochrome p450 epoxygenase metabolite of arachidonic acid (AA). It is presently unknown how these distinct activators converge on opening of the channel. Here, we demonstrate that blockers of phospholipase A(2) (PLA(2)) and cytochrome p450 epoxygenase inhibit activation of TRPV4 by osmotic cell swelling but not by heat and 4alpha-phorbol 12,13-didecanoate. Mutating a tyrosine residue (Tyr-555) in the N-terminal part of the third transmembrane domain to an alanine strongly impairs activation of TRPV4 by 4alpha-phorbol 12,13-didecanoate and heat but has no effect on activation by cell swelling or AA. We conclude that TRPV4-activating stimuli promote channel opening by means of distinct pathways. Cell swelling activates TRPV4 by means of the PLA(2)-dependent formation of AA, and its subsequent metabolization to 5',6'-epoxyeicosatrienoic acid by means of a cytochrome p450 epoxygenase-dependent pathway. Phorbol esters and heat operate by means of a distinct, PLA(2)- and cytochrome p450 epoxygenase-independent pathway, which critically depends on an aromatic residue at the N terminus of the third transmembrane domain.

[Repair and revision 9. Peripheral trigeminal nerve injury]. / Reparatie en revisie 9. Perifeer trigeminaal zenuwletsel.

A review is given about long-term incidence of sensory disturbance in the areas of innervation of the n. trigeminus for different types of trauma and/or treatment. Diagnosis, clinical course and possible types of treatment are in addition reviewed. Regarding diagnosis, the outcome of a test on sensory function is not always related to the degree of nerve damage because methods differ in the type of afferent nerve fibers of which function is tested, and some specificity might occur in nerve damage, i.e. either thick or thin afferent fibers might be predominantly affected at a particular time. An initial quick testing of sensory function is recommended. This testing includes examining two sensory modalities, which are related to functioning of thick and thin afferent fibers respectively and which have a dichotomous yes/no outcome on the incidence of a pronounced sensory disturbance.

Information on infraorbital nerve damage from multitesting of sensory function.

Sensory disturbance following orbitozygomatic complex fractures was studied in 65 patients from 4 treatment groups which represented potentially varying degrees of sensory disturbance. The fracture-type-dependent treatments were: no surgical intervention (n = 20), closed reduction with or without wire fixation (n = 17), open reduction with miniplate fixation (n = 15) and/or reconstruction of the orbital floor (n = 13). In order to assess the sensory function of different classes of afferent fibres, several methods of sensory testing were applied. On average 6.3 months after treatment, the patient's report was obtained, and tests regarding touch, two methods of two-point discrimination, and cold were applied on the cheek and upper lip. The degree of sensory disturbance was method-dependent. In patients who underwent closed reduction, pronounced levels of positive correlation occurred between results from different tests or from both test sites. The levels of these correlations were, in general, low for all other treatments. These findings suggest that afferent fibres of both large and small diameter tended to be permanently damaged in the patient group with closed reduction. In contrast, the types of sensory afferent fibres that were involved in the trauma and/or their recovery were highly variable within patients and sites for all other treatment groups.

Infraorbital nerve function following treatment of orbitozygomatic complex fractures. A multitest approach.

Sensory disturbance following orbitozygomatic complex fractures was studied in 65 patients in relation to type of fracture and method of treatment. The fracture-type-dependent treatments were: no surgical intervention (n = 20), closed reduction with or without wire fixation (n = 17), open reduction with miniplate fixation (n = 15) and/or reconstruction of the orbital floor (n = 13). Several methods were applied to assess sensory function, on average 6.3 months after treatment, i.e. the patient's report and tests regarding touch, two methods of two-point discrimination, and cold, all applied on the cheek and upper lip. The various examinations indicated that, on average, the long-term sensory disturbance was most pronounced and severe in patients who underwent closed reduction without miniplate fixation. As the sensory disturbance of patients with open reduction and miniplate fixation approached the base-line level of patients for whom surgical intervention was not indicated, open reduction with miniplate fixation can be recommended as treatment for frontozygomatic suture fractures. The degree of sensory disturbance of patients who underwent orbital floor reconstruction was intermediate compared to patients with closed and open reduction respectively.

[Simple assessment of trigeminal nerve injury]. / Eenvoudig onderzoek naar letsel van de nervus trigeminus.

This paper describes a simple method to assess trigeminal nerve injury. An easy and feasible technique, in particular for the dental surgeon, is scanning the area with altered sensation as indicated by the patient. It is important to refer the eligible patient in time for microsurgical repair of the damaged nerve.

Recovery of sensation in the radial forearm free flap in oral reconstruction.

The purpose of this study was to find out to what extent sensory function recovers in a free radial forearm flap used for intraoral reconstruction after surgery for oral cancer. In 40 free radial forearm flaps we investigated the perception of light touch, two-point discrimination, pain, directional sensation, and temperature between 6 months and 11 years after flap transfer to the oral cavity. Four flaps (10 percent) were anesthetic, 21 flaps (52.5 percent) recovered partly, and 15 flaps (37.5 percent) had perception of all sensory modalities tested in at least two-thirds of the flap area. All patients with positive sensation in the surrounding area subsequently had good sensory recovery in the flap. This suggests that recovery of sensation in a nonreinnervated free flap is due to nerve ingrowth from the surrounding mucosa. The present results suggest that sensory function in intraoral free radial forearm flaps returns again. Further study is necessary to define the use of neurofasciocutaneous radial forearm flaps in reconstruction of the oral cavity.

Morbidity of the infraorbital nerve following orbitozygomatic complex fractures.

Acute sensory disturbances in the distribution of the infraorbital nerve are recognised signs present in patients with orbitozygomatic complex fractures. Fifty consecutive patients with unilateral orbitozygomatic complex fractures were evaluated with regard to the long-term infraorbital nerve sensory function. The highest incidence of long-term neurosensory deficits occurred in fractures with an undistracted frontozygomatic suture. This is in complete agreement with the distribution of long-term neurosensory deficits regarding the method of treatment for orbitozygomatic complex fractures. In our series slightly more than one-third of the patients had third or fourth degree nerve injuries, according to Sunderland's classification, to the infraorbital nerve following orbitozygomatic complex fractures. This outcome should influence the management of orbitozygomatic complex fractures. With regard to fixation of unstable malar fractures in relation to sensory recovery of the infraorbital nerve, miniplate osteosynthesis is recommended as opposed to wire fixation in all unstable bone fractures when there is displacement. Furthermore, open reduction and fixation of an orbitozygomatic complex fracture offer a better prognosis for complete recovery of the infraorbital nerve function than elevation only with or without Kirschner wire fixation.

A reappraisal of the platysma myocutaneous island flap. A follow-up study of the functional outcome after reconstruction of the floor of the mouth.

The functional results of primary reconstruction of the floor of the mouth after ablative surgery for oral cancer using a platysma myocutaneous island flap are reviewed. Seventeen patients who had simultaneous neck dissection, tumor resection, and reconstruction were evaluated. It appears from this study that primary reconstruction of the floor of the mouth with a platysma flap is not ideal. This is believed to be due partly to the high occurrence of direct, postoperative complications.

Magnetic resonance assessment of microvascular patency in reimplanted rabbit ears.

RATIONALE AND OBJECTIVES: Magnetic resonance angiography (MRA) provides a means of noninvasive vascular imaging of microvascular vessels. Before conducting comparative studies and value assessments of a new method, it is necessary to evaluate the reproducibility and reliability of the technique. In an experimental study with five rabbits, we investigated the feasibility of MRA imaging of microsurgical vessels. We also attempted to demonstrate the reproducibility of the method. METHODS: We performed MRA imaging of the vascular tree of five New Zealand white rabbit ears, including normal ears, after microvascular reimplantation of the ear and in occlusion experiments on the ear. Scans of four reimplanted ears were performed after the microvascular procedure. In four occlusion experiments, the central vessels were totally occluded by a ligature, and scans were carried out prior to and immediately after occlusion. We used a fast imaging with steady-state precession (FISP) three-dimensional (3-D) rephased-dephased sequence (28-msec repetition time [TR], 18-msec echo time [TE], and a 20 degrees flip angle). RESULTS: In normal rabbit ears and in the reimplantation cases, MRA imaging was able to show the flow within the vascular tree. In the reimplanted ears, MRA images confirmed patency in all anastomosed vessels. The diagnosis of occlusion appeared to be secure in the fully completed experiments (two of four) when it was based on the absence of a signal in the occluded vessels. Because of poor image quality during preligation scanning, we prematurely canceled two experiments. CONCLUSIONS: This study demonstrates that MRA imaging could correctly identify 1-mm vascular channels. Because of the long acquisition time, motion could compromise the reliability of the technique in human subjects.

Autogenous transplantation of third molars in irradiated jaws--a preliminary report.

Our experience with third molar autotransplants in 2 patients, into an area irradiated at an early age, is described and discussed. It is shown that such autotransplantations are possible.

Assessment of trigeminal nerve function by means of short-latency somatosensory evoked potentials after microneurosurgical repair.

In order to evaluate accurately trigeminal nerve damage and the response to microneurosurgical treatment, a reproducible, objective test of trigeminal nerve function is required. This study investigates the use of somatosensory evoked potentials as an objective monitor of trigeminal nerve function after microneurosurgical repair. We examined 10 patients, all but 1 treated for gnathic disorders, in whom a severe iatrogenic injury to the inferior alveolar nerve occurred unilaterally. One patient underwent partial mandibulectomy with sacrifice of the nerve because of a malignant tumour. A significant difference in trigeminal somatosensory evoked potential latencies after stimulation of the normal side of the lower jaw compared with the response after stimulation of the affected side was to be expected. Immediate microneurosurgical repair was carried out in 7 patients. The trigeminal somatosensory evoked potential latencies after right and left sided stimulation of the mandible did not differ significantly after subjective successful microneurosurgical repair. Somatosensory evoked potential testing appears to represent an objective method of evaluating trigeminal nerve function, in particular in relation to microneurosurgical procedures. The results of trigeminal testing should improve after technical refinement.