Optimization of laboratory procedures for intrauterine insemination: survey of methods in relation to clinical outcome.

BACKGROUND: There is a wide practice variation of used methods and outcomes in IUI in fertility laboratories. Standardization of the IUI procedure is important for reducing inconsistency among laboratories in counseling infertile couples and in pregnancy results. The aim of the study was to evaluate the currently used laboratory procedures of IUI in Dutch fertility laboratories and their effect on IUI pregnancy results. Additionally, the methods for semen analysis (SA) were evaluated, as SA is related to IUI in terms of inseminated sperm number and IUI counseling. MATERIAL AND METHODS: This questionnaire survey study was sent to laboratories participating in the Dutch external quality control program for semen analysis (SKML) and consisted of 46 questions concerning laboratory management, methods for semen analysis and IUI, and clinical results. The results were analyzed using univariable and multivariable logistic regression models. RESULTS: A total of 52 laboratories (out of 99) provided information on used methodologies for SA or laboratory procedures of IUI and the organization of the laboratory. A wide variability was confirmed in used methods for both SA and IUI. Evaluation of pregnancy results obtained during 3 years (2013-2015) showed that specific used laboratory methods have a significant effect on the probability of becoming pregnant. DISCUSSION AND CONCLUSION: Important to remark is that in this survey study cycle-specific data, including variables of the individual couples (age, stimulation protocol, etc), were not included and may have effects on the results. The reported results provide an overview of the current practice performance; however, the organization of fertility laboratories is changing rapidly. The use of standardized methods in IUI is important for optimizing the performance of care and improving pregnancy results. The knowledge on used procedures, however, is limited, and further research on factors involving SA and the IUI procedure is necessary.

Techniques used for IUI: is it time for a change?

STUDY QUESTION: Are the guidelines for the technical aspects of IUI (WHO, 2010) still in accordance with the current literature? SUMMARY ANSWER: In general, the laboratory guidelines of the World Health Organization (WHO) are a suitable protocol, although the evidence is not always conclusive and some changes are advisable. WHAT IS KNOWN ALREADY: Lack of standardization of the technical procedures required for IUI might result in inter-laboratory variation in pregnancy rates. Most centers still use their own materials and methods even though some guidelines are available. STUDY DESIGN, SIZE, DURATION: A structural review focusing on the association between pregnancy rates and the procedures of semen collection (e.g. ejaculatory abstinence, collection place), semen processing (e.g. preparation method, temperature during centrifugation/storage), insemination (e.g. timing of IUI, bed rest after IUI) and the equipment used. PARTICIPANTS/MATERIALS, SETTING, METHODS: A literature search was performed in Medline and the Cochrane library. When no adequate studies of the impact of a parameter on pregnancy results were found, its association with sperm parameters was reviewed. MAIN RESULTS AND THE ROLE OF CHANCE: For most variables, the literature review revealed a low level of evidence, a limited number of studies and/or an inadequate outcome measure. Moreover, the comparison of procedures (i.e. semen preparation technique, time interval between semen, collection, processing and IUI) revealed no consensus about their results. It was not possible to develop an evidence-based, optimal IUI treatment protocol. LIMITATIONS, REASONS FOR CAUTION: The included studies exhibited a lack of standardization in inclusion criteria and methods used. WIDER IMPLICATIONS OF THE FINDINGS: This review emphasizes the need for more knowledge about and standardization of assisted reproduction technologies. Our literature search indicates that some of the recommendations in the laboratory guidelines could be adapted to improve standardization, comfort, quality control and to cut costs. STUDY FUNDING/COMPETING INTEREST(S): The Dutch Foundation for Quality Assessment in Medical Laboratories (SKML), Nijmegen, The Netherlands. S.K. and W.N. have no conflicts of interest to disclose. C.B. and A.W. are members of the board of the SKML. With a grant from SKML, L.L. was paid for her time to perform the research and write the publication. D.B. received grants from Merck Serono, Ferring and MSD, outside the submitted work. REGISTRATION NUMBER: N/A.

Few adverse effects of long-term creatine supplementation in a placebo-controlled trial.

Although oral creatine supplementation is very popular among athletes, no prospective placebo-controlled studies on the adverse effects of long-term supplementation have yet been conducted. We performed a double-blind, placebo-controlled trial of creatine monohydrate in patients with the neurodegenerative disease amyotrophic lateral sclerosis, because of the neuroprotective effects it was shown to have in animal experiments. The purpose of this paper is to compare the adverse effects, and to describe the effects on indirect markers of renal function of long-term creatine supplementation. 175 subjects (age = 57.7 +/- 11.1 y) were randomly assigned to receive creatine monohydrate 10 g daily or placebo during an average period of 310 days. After one month, two months and from then on every fourth month, adverse effects were scored using dichotomous questionnaires, plasma urea concentrations were measured, and urinary creatine and albumin concentrations were determined. No significant differences in the occurrence at any time of adverse effects due to creatine supplementation were found (23 % nausea in the creatine group, vs. 24 % in the placebo group, 19 % gastro-intestinal discomfort in the creatine group, vs. 18 % in the placebo group, 35 % diarrhoea in the creatine group, vs. 24 % in the placebo group). After two months of treatment, oedematous limbs were seen more often in subjects using creatine, probably due to water retention. Severe diarrhoea (n = 2) and severe nausea (n = 1) caused 3 subjects in the creatine group to stop intake of creatine, after which these adverse effects subsided. Long-term supplementation of creatine did not lead to an increase of plasma urea levels (5.69 +/- 1.47 before treatment vs. 5.26 +/- 1.44 at the end of treatment) or to a higher prevalence of micro-albuminuria (5.4 % before treatment vs. 1.8 % at the end of treatment).

[High levels of carcinoembryonic antigen in a woman with hypothyroidism]. / Hoge concentratie van carcino-embryonaal antigeen bij een vrouw met hypothyreoïdie.

A 53-year-old woman was referred to the outpatient clinic for Internal Medicine, due to an elevated serum concentration of carcinoembryonic antigen (CEA). Hypothyroidism was diagnosed. Following replacement therapy with levothyroxin, the serum concentrations of thyroid stimulating hormone (TSH) and CEA decreased to near-normal levels. No malignancy was found during the remainder of the treatment period. A decreased hepatic clearance of CEA seemed to be the most likely explanation for the observed high CEA concentration in this patient with hypothyroidism. An increased CEA concentration may occur in association with certain malignancies, as well as with non-neoplastic disorders, such as hypothyroidism. As CEA has a low tumour specificity, routine assessment of CEA is not advocated for diagnostic evaluation.

[Hypercalcemia due to chronic vitamin A use by an elderly patient with renal insufficiency]. / Hypercalciëmie door chronisch vitamine-A-gebruik bij een bejaarde patiënte met nierinsufficiëntie.

An 86-year-old woman presented with anorexia, thirst and nycturia. Laboratory results revealed a hypercalcaemia with renal failure. The patient used 1-6 vitamin A-D tablets daily (1 tablet contains 600 IU retinol palmitate and 200 IU cholecalciferol). The diagnosis was: hypercalcaemia due to chronic vitamin A ingestion. This diagnosis was supported by the finding of the elevated vitamin A concentration in the patient's serum and the exclusion of other causes of hypercalcaemia. In chronic vitamin A ingestion risk factors for vitamin A toxicity are age, body weight and renal insufficiency. The hypercalcaemia caused by chronic vitamin A ingestion is explained through the up-regulation of osteoclasts by retinol metabolites.

An assessment of intraocular pressure rise in patients with gas-filled eyes during simulated air flight.

PURPOSE: To investigate the safety of aircraft flight for patients with small volumes of residual postoperative intraocular gas. DESIGN: Nonrandomized comparative trial. PARTICIPANTS: Seventeen eyes (nine gas filled and eight control eyes) of nine patients and one eye of one control subject were tested. METHODS: Patients with postoperative intraocular gas and the control subject were tested in the controlled environment of a hypobaric chamber to simulate the cabin depressurization associated with a typical commercial aircraft flight. Before, during, and after a simulated flight, the intraocular pressure (IOP) in the gas-containing and contralateral eyes was tested using the Perkins (Edinburgh, UK) and Tono-Pen XL (Jacksonville, FL) tonometers. MAIN OUTCOME MEASURES: The absolute and percentage change in IOP with varied cabin pressurization. RESULTS: Of the nine patients with intraocular gas, seven had 10% to 15% gas volume and two had 20% gas volume. In the 10% to 15% gas volume group, the IOP rose by an average of 109% from baseline during ascent to an average cabin altitude of 7429 feet above sea level. The IOP dropped to an average of 30% above baseline IOP during the cruise phase and further decreased to an average of 38% below baseline IOP on return to baseline altitude. In the 20% gas volume group, the IOP rose by an average of 84% from baseline during ascent to an average cabin altitude of 3400 feet above sea level. The IOP dropped to an average of 42% below baseline IOP on return to baseline altitude. The IOP in the contralateral control eyes did not vary with altitude changes. No patient experienced pain or visual loss during the experiments. CONCLUSIONS: Our results demonstrate that IOP may rise significantly in gas-filled eyes during simulated air flight, supporting the current conservative recommendation against air travel for most patients with intraocular gas bubbles. Further testing is warranted to develop a more objective measure of intraocular gas volume estimation and to define better the tolerability of aircraft flight for patients with intraocular gas.

alpha-thalassaemia as a result of a novel splice donor site mutation of the alpha1-globin gene.

We describe the characterization of an alpha+-thalassaemia determinant as a result of a transition of G-->A of the donor splice consensus site sequence of the first intron of the alpha1-globin gene (alpha1IVS I-1). The mutation was found in combination with the South-East Asian alpha0-thalassaemia deletion in an haemoglobin (Hb)H patient and her sister, both of Thai origin. Sequencing of the abnormally spliced mRNA product revealed the presence of a cryptic splice site in exon 1 of the alpha1-globin gene. No normally spliced alpha1mRNA was detected. The abnormally spliced mRNA product from the alpha1-gene carrying the mutation does not lead to functional protein and causes a mild HbH-disease phenotype when in combination with the deletion type alpha0-thalassaemia.

Implementation of the national cervical cancer screening in general practice and feasibility of a general practice-based call system: the GP's opinion.

Thus far, the response to the nationwide screening programme for cervical cancer in The Netherlands, which was started in 1989, has been disappointing. One way to improve response is to involve general practitioners in the call system. A postal survey was conducted to review the implementation of the current screening programme in general practice and to examine the willingness of general practitioners to participate in a general practice-based call system. The response rate to the survey was 90%. The general practitioners were dissatisfied with follow-up, cost and time spent and compliance of women. Of all respondents 60% had already set up a call system within the practice or were willing to do so; another 31% were willing to participate in a regionally organized practice-based call system. On the basis of the results of this study a centralized general practice-based call system is recommended. The next step is to study the applicability of this system in a pilot programme.

[Combined alpha and beta thalassemia in a Chinese family in The Netherlands]. / Gecombineerde alpha- en beta-thalassemie bij een Chinese familie in Nederland.

In a Chinese family living in The Netherlands alpha 0- and beta-thalassaemia occur singly and in combined form. All members of the family are moderately anaemic and show the characteristic haematological abnormalities of thalassaemia carriers. The nature of the alpha 0-thalassaemia defect was shown at the molecular level to be a deletion of the South East Asian type, which removes about 20 kb of DNA spanning both alpha genes in cis. The chromosome carrying the beta-thalassaemia mutation was identified using RFLPs (restriction enzyme fragment length polymorphisms). The combined heterozygosity for alpha 0- and beta-thalassaemia results in a phenotype virtually indistinguishable from heterozygous beta-thalassaemia, except for the almost balanced globin chain synthesis.

Erythrocyte transketolase, a new semi-automated method.

This paper describes a method to determine transketolase activity in erythrocytes, with or without addition of thiamine-pyrophosphate, by quantitating the formation of glucose-6-phosphate forming during the incubation of hemolysed blood with ribose-5-phosphate. Glucose-6-phosphate is determined enzymatically, after deproteinisation of the sample, using a centrifugal fast analyser. The proposed method gave a correlation of r = 0.89 with an accepted colorimetric method. Reference values for blood are in the range 32--101 U/l.