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PubMed1998

Maternal serum androgens in human pregnancy: early increases within the cycle of conception.

Previous studies have demonstrated elevations in testosterone and androstenedione initiated within the cycle of conception in pregnant non-human primates, and minimal data in the human support the same picture. In the present study we have investigated a group of patients scheduled for artificial insemination with regular menstrual cycles. For this study all patients provided blood samples at 5 days after the luteinizing hormone (LH) surges and daily through the luteal phase and into early pregnancy (n = 12). Patients who did not become pregnant served as normal controls (n = 9). We have measured 17-hydroxyprogesterone (17-OHP) as a marker of luteal activity not obscured by progesterone within the cycle of conception and testosterone and androstenedione as the major androgens. There were no significant changes in testosterone and androstenedione in the non-pregnant controls, but both testosterone and androstenedione were significantly elevated in the pregnant luteal phase, with the first increases occurring at 15 and 14 days respectively after the LH surge. Three of 12 pregnant patients did not demonstrate a dramatic increase in either testosterone or androstenedione and when examined more carefully a corresponding lack of increase in 17-OHP in those same subjects indicated less than optimal luteal activity, suggesting that these androgens were products of the corpus luteum. In three subjects in which consecutive non-pregnant and pregnant cycles were followed there was a dramatic increase from the non-pregnant luteal phase to the pregnant luteal phase indicating that the more important observation may be the concentrations of androgens in the conceptive luteal phase compared to some baseline, either previous luteal phase or even follicular phase. We have also studied changes in dehydroepiandrosterone sulphate and found that there was no significant contribution to this increase in androgens in early conception. These studies demonstrate a significant increase in both testosterone and androstenedione presumably of ovarian, specifically luteal, origin and that adrenal androgen production is not a factor in these changes.

17-alpha-Hydroxyprogesterone↗
PubMed2000

The prognostic power of the post-coital test for natural conception depends on duration of infertility.

Controversy about the value of the post-coital test (PCT) has prompted us to re-analyse data from 207 couples, originally studied between 1982 and 1983, with at least 12 months' infertility at presentation, complete diagnostic information and exclusion of female factors, to clarify the effect of duration of infertility on the prediction of conception. In couples with less than 3 years infertility and a positive PCT, 68% conceived within 2 years compared with 17% of those with a negative result. After 3 years, corresponding rates were 14% and 11%. The relative risks of conception [95% confidence interval (CI)] calculated using the Cox's proportional hazards model were 0.23 (0.12-0.43) for a negative PCT (reference positive PCT) and 0.25 (0.13-0.51) for more than 36 months infertility (reference 12-23 months). Semen analysis had no extra predictive power given the duration of infertility and the PCT. The PCT is an effective predictor of conception where defined female causes of infertility are absent and duration of infertility is less than 3 years. Once infertility is prolonged (beyond 3 years) the conception rate is low even with a positive test because a large proportion of couples remaining childless so long have true unexplained infertility. Use of the PCT will enable clinicians to allocate scarce, expensive and invasive resources effectively.

Adult↗
PubMed2002

Prolonged use of oral contraception before a planned pregnancy is associated with a decreased risk of delayed conception.

BACKGROUND: The aim of this study was to investigate the association of total duration of oral contraceptive usage with time to conception. METHODS: This was a prospective study of 8497 planned pregnancies drawn from a population that recruited 85% of eligible couples in South-West England who were expecting a baby in a 21 month period. Self-completion questionnaires were administered at 18 weeks gestation to ascertain parity, paternity, co-habitation, use of the contraceptive pill, smoking and alcohol status, educational achievement, height, weight and time taken to conceive. Logistic regression was used to identify factors independently related to conception in < or =12 months. RESULTS: Of the participants, 74% conceived in < or =6 months, 14% in 6-12 months and 12% after 1 year. Previous prolonged oral contraceptive usage was statistically significantly associated with a decreased risk of delayed conception. Prolonged use of oral contraception was also associated with improved fecundity independent of other factors. Selection bias due to particularly fertile women using oral contraceptives is unlikely because similar odds ratios were calculated for nulligravid women. CONCLUSIONS: Women who have prolonged use of oral contraceptives might be reassured that they will not be disadvantaged in terms of time taken to achieve conception.

Adult↗
PubMed2003

Successful conception following Fallopian tube recanalization in infertile patients with a unilateral proximally occluded tube and a contralateral patent tube.

BACKGROUND: There are many published case reports of successful conception following transcervical Fallopian tube recanalization (T-FTR) in patients with bilateral proximally occluded Fallopian tubes. However, no serial trials have been published with respect to successful conception following unilateral tubal recanalization in infertile patients with a unilateral proximally occluded tube and a contralateral patent tube. This study was designated to analyse the success rate of T-FTR and the pregnancy rate due to natural fertilization in the lumen of the recanalized tube in these patients. METHODS: We have encountered only 11 patients with this abnormality in our department in the past 10 years. T-FTR with fluoroscopic guidance was performed in these patients, confirmed by at least two hysterosalpingographies to exclude tubal spasm. The uterine catheter devised by us was used during the procedure. RESULTS: All 11 Fallopian tubes were successfully opened by T-FTR. In the six patients who conceived, a preovulatory follicle was demonstrated on the side of the cannulated tube during the conception. The success rate of recanalization, the pregnancy rate due to fertilization in the lumen of the recanalized tube and the successful delivery rate were 100, 55 and 36% respectively. CONCLUSIONS: Our findings suggest that a functional and/or organic disorder in the patent tube resulted in infertility in patients with unilateral proximal tubal obstruction. Our results further show that recanalization of occluded tubes is an effective treatment. Thus, recognition of successful conception following T-FTR in these patients will be beneficial to our clinical approach to this infertile condition.

Adult↗
PubMed2003

The male disadvantage and the seasonal rhythm of sex ratio at the time of conception.

BACKGROUND: In accordance with a presumed greater fragility of male versus female pregnancies, we tested whether sex ratio (male/female ratio) of vital pregnancies is higher in seasons more favourable for reproduction. METHODS: A retrospective study was performed on 14,310 births which had occurred in our institute between 1995-2001. For each single pregnancy the time of conception was calculated by the last menstrual period recall and confirmed or redefined by ultrasound in 95.8% of cases. The sex ratio of 199,454 pregnancies which had occurred in the Modena County between 1936-1998 was also stratified according to the month of birth. RESULTS: Sex ratio of institutional deliveries was 0.511 and was identical to that obtained from the County registry. Sex ratio at birth did not show a significant seasonal variation. By contrast, sex ratio calculated at time of conception showed a seasonal rhythm, with amplitude of 2.4% and peak values in October (confidence interval: +/-43 days). The rhythm was in phase with the rhythm of conception that showed peak values in September (confidence interval: +/-37 days) and an amplitude of 7%. CONCLUSIONS: The superimposition of the phase of sex ratio and conception rhythms supports the contention that more males than females are conceived in seasons with more favourable reproductive conditions.

Female↗
PubMed2004

Mucus observations in the fertile window: a better predictor of conception than timing of intercourse.

BACKGROUND: Intercourse results in a pregnancy essentially only if it occurs during the 6-day fertile interval ending on the day of ovulation. The strong association between timing of intercourse within this interval and the probability of conception typically is attributed to limited sperm and egg life times. METHODS: A total of 782 women recruited from natural family planning centres in Europe contributed prospective data on 7288 menstrual cycles. Daily records of intercourse, basal body temperature and vaginal discharge of cervical mucus were collected. Probabilities of conception were estimated according to the timing of intercourse relative to ovulation and a 1-4 score of mucus quality. RESULTS: There was a strong increasing trend in the day-specific probabilities of pregnancy with increases in the mucus score. Adjusting for the mucus score, the day-specific probabilities had limited variability across the fertile interval. CONCLUSIONS: Changes in mucus quality across the fertile interval predict the observed pattern in the day-specific probabilities of conception. To maximize the likelihood of conception, intercourse should occur on days with optimal mucus quality, as observed in vaginal discharge, regardless of the exact timing relative to ovulation.

Adult↗
PubMed2004

Follicular diameters in conception cycles with and without multiple pregnancy after stimulated ovulation induction.

BACKGROUND: Controlled ovulation induction and intrauterine insemination (OI-IUI) is associated with multiple pregnancies, which are a cause of much concern. No reliable datasets have shown clear criteria for predicting multiple pregnancy. The aim of this study was to eliminate a number of variables by examining only conception cycles to determine ultrasound criteria posing risks of multiple pregnancy. METHODS: 112 OI-IUI conception cycles (multiple pregnancy rate 19.6%) were analysed retrospectively to identify factors that may be used to evaluate multiple pregnancy risk. Analyses of ultrasound data on the day of hCG administration allowed study of the role of primary, secondary and tertiary follicle diameters (FD). RESULTS: There were no multiple pregnancies in cases where there was a single FD > or = 14 mm, and no higher-order pregnancies where the tertiary follicle measured <14 mm. Follicles with an FD of 15 mm showed an 8% attributable implantation rate. CONCLUSIONS: Revision of the criteria for administration of the ovulatory dose of hCG should include the concept that follicles of 15 mm diameter may yield a pregnancy. We suggest that rigorous application of such criteria (critical FD of 16 mm combined with secondary FD evidence) will not reduce the programme pregnancy rate, but will reduce the incidence of multiple conceptions.

Adult↗
PubMed2005

Is controlled ovarian stimulation in intrauterine insemination an acceptable therapy in couples with unexplained non-conception in the perspective of multiple pregnancies?

BACKGROUND: Controlled ovarian stimulation (COS) with intrauterine insemination (IUI) is a common treatment in couples with unexplained non-conception. Induction of multifollicular growth is considered to improve pregnancy outcome, but it contains an increased risk of multiple pregnancies and ovarian hyperstimulation syndrome. In this study the impact of the number of follicles (>14 mm) on the ongoing pregnancy rate (PR) and multiple PR was evaluated in the first four treatment cycles. METHODS: A retrospective cohort study was performed in all couples with unexplained non-conception undergoing COS-IUI in the Academic Hospital of Maastricht. The main outcome measure was ongoing PR. Secondary outcomes were ongoing multiple PR, number of follicles of >or=14 mm, and order of treatment cycle. RESULTS: Three hundred couples were included. No significant difference was found in ongoing PR between women with one, two, three or four follicles respectively (P=0.54), but in women with two or more follicles 12/73 pregnancies were multiples. Ongoing PR was highest in the first treatment cycle and declined significantly with increasing cycle order (P=0.006), while multiple PR did not change. CONCLUSIONS: In COS-IUI for unexplained non-conception, induction of more than one follicle did not improve the ongoing PR, but increased the risk of multiple pregnancies. Multiple PR remained high in the first four cycles with multifollicular stimulation. Therefore, in order to reduce the number of multiple pregnancies, in all IUI cycles for unexplained non-conception monofollicular growth should be aimed at.

Cohort Studies↗
PubMed2006

Placental pathology of recurrent spontaneous abortion: the role of histopathological examination of products of conception in routine clinical practice: a mini review.

BACKGROUND: Histopathological examination of products of conception from miscarriages is part of routine clinical practice. The extent of additional clinically relevant information provided by this investigation in the setting of recurrent spontaneous abortion remains uncertain. METHODS: Review of the literature was performed to identify studies reporting on findings of histological examination of routinely obtained products of conception in the setting of recurrent spontaneous abortion. The initial search identified 312 potential references, but 300 were excluded on further examination due to lack of data on specific histopathological findings in routine products of conception specimens from patients with recurrent spontaneous abortion. The 12 included studies indicated that such examination may identify hydatidiform moles, villous dysmorphic features suggesting fetal aneuploidy, chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition and impaired trophoblast invasion. However, in most cases, morphological assessment cannot reliably determine the cause of the miscarriage or distinguish recurrent from sporadic miscarriage. Studies reporting on the use of additional immunohistochemical methods do not currently provide additional clinically useful diagnostic or prognostic information. CONCLUSION: Routine histological examination of products of conception in the setting of recurrent spontaneous abortion can provide important clinical information in a minority of cases.

Abortion, Habitual↗
PubMed1995

Health as an analogical concept.

This article examines the normative structure of the concept of health and tries to suggest an account of it in a phenomenological-hermeneutic framework. It is argued that the concept of health has a logical priority to illness, though the latter has an experiential priority. The fundamental feature of the concept of health as discussed in the literature is initially recognized in the notion of 'norm', in both the bio-statistical and normative-ideal sense. An analysis of this body of literature reveals some weaknesses in bio-statistical definitions of health as well as in those normative ones which endorse a value-relativity thesis. An approach based on the analogical structure of language is then advanced. In this framework, the notion of biological normativeness proposed by G. Canguilhem is connected with an analysis of the language of health through etymologies. It is argued that health can be characterized as an analogy of 'plenitude', which is the common ideal reference of the various health-concepts. The analogical structuring of language allows the recognition of different levels of meaning, and therefore of different kinds of normativeness (biological, mental, social, moral). Some hints of a theory of health deriving from this framework are then given.

Attitude to Health↗
PubMed2003

Investigations into the concept of a threshold for topoisomerase inhibitor-induced clastogenicity.

Although the application of the concept of a threshold to risk assessment is widespread, there remains little experimental evidence for the existence of thresholds for genotoxic compounds, other than aneugens. The clastogenicity of topoisomerase inhibitors is believed to result from the transient stabilization of the topoisomerase enzyme with DNA during the catalytic cycle. This leads to the formation of a stabilized cleavage complex, which, in turn, may result in the formation of a DNA strand break. This indirect mechanism of clastogenicity is the basis for the concept of threshold for this class of drug. Using micronucleus induction in L5178Y mouse lymphoma cells as a genotoxic end-point, a three pronged approach was used to examine whether the concept of a threshold for clastogenicity could be demonstrated for topoisomerase type II inhibitors in vitro. This involved (i) the study of mechanism (TARDIS assay), (ii) hypothesis testing versus estimation (i.e. scoring up to 10,000 cells/treatment at concentrations immediately above and below the NOEL for micronucleus induction) and (iii) statistical modelling of the concentration-response curves for micronucleus induction. Several topoisomerase type II inhibitors were investigated with varying clastogenic potencies (etoposide = doxorubicin < genistein < ciprofloxacin). Pragmatic thresholds for clastogenicity in L5178Y cells were defined at 0.00236 microg/ml for etoposide, 0.00151 microg/ml for doxorubicin, 1 microg/ml for genistein and 50 microg/ml for ciprofloxacin. In addition, it was demonstrated that etoposide-induced clastogenicity was concentration and time dependent. These results, along with mechanistic data showing that all of the compounds induced concentration-dependent increases in the formation of topoisomerase II stabilized cleavage complexes, provide a weight of evidence to support a threshold concept for clastogenicity with topoisomerase II poisons.

Animals↗
PubMed1990

Outcome of pregnancies resulting from assisted conception.

With the increasing practice of assisted conception, the health of the resulting children is becoming an increasingly important issue. Experience with four thousand children conceived by IVF or GIFT indicates that multiple pregnancy, which frequently results from assisted conception, is the main determinant of complications during pregnancy and of the health of the children at the time of birth. Overall malformation rates are similar to those in the country as a whole. There are, however, still insufficient numbers of children studied to draw firm conclusions about the risk of specific types of malformations. This will require the continued monitoring of children resulting from assisted conception, and the continued co-operation of many individuals and centres practising assisted conception.

Adult↗
PubMed1996

Effects of a behavioural rhythm on conception probability and pregnancy outcome.

This paper concerns a behaviour-driven weekday rhythm in conception rates in a large natural human population. From 1978 to 1991, North Carolina normal live single births arose from menstrual cycles which began on Monday in clear excess over other weekdays. Cycles beginning on Friday were also in excess. Cycles starting on Saturday and Sunday, or Wednesday and Thursday, each represented significantly less than one in seven of weekly totals. The source of the observed synchrony was a Sunday morning peak of coital frequency. Average cycles which began on Monday had their most fertile day on the most likely day for intercourse, translating a weekly insemination rhythm into a weekly conception rate rhythm. The secondary conception peak in Friday-onset cycles increased with age, to become the major peak for mothers aged > 30 years. We interpret this to represent a previously unreported second type of cycle with a modal follicular phase length of 10 days, the frequency of which increases with age. Several large groups of anomalous human births depart significantly from the weekday rhythm of normal conceptions. These outcomes parallel results of experimental interference with fertilization timing in estruative mammals. We believe that this implicates anomalous fertilization timing in several of the most numerous anomalies of human prenatal development.

Behavior↗
PubMed1993

Effects of age, gravidity and male infertility status on cumulative conception rates following artificial insemination with cryopreserved donor semen: analysis of 2998 cycles of treatment in one centre over 10 years.

The effects of age, gravidity and male infertility status on cumulative conception rates after donor insemination were investigated in an analysis of 2998 treatment cycles undertaken on 443 patients. It was found that the cumulative conception rates after 3, 6 and 12 cycles of treatment were 21, 40 and 62% respectively for patients < 30 years of age compared with 17, 26 and 44% for those aged > or = 30 years (P = 0.008). There was also a significant difference (P < 0.001) in results depending on course of treatment and the cumulative conception rates were 19% after 3 cycles, 33% after 6 cycles and 54% after 12 cycles of treatment in the first course of treatment compared with 40, 67 and 79% respectively in those who returned for subsequent courses of treatment after having achieved a donor insemination pregnancy in the first treatment course. Gravidity and male infertility status (azoospermia or oligozoospermia/asthenozoospermia) did not significantly affect the cumulative conception rates.

Adult↗
PubMed2003

Proline versus charge concept for protein stabilization against proteolytic attack.

The virtue of the so-called 'proline concept' and the 'charge concept' for stabilizing protease-susceptible regions of a protein structure was compared on bovine pancreatic ribonuclease A. Alanine 20 and serine 21, both of which are located in a loop that is susceptible to the unspecific proteases subtilisin Carlsberg, subtilisin BPN', proteinase K and elastase, were replaced with proline or lysine by site-directed mutagenesis. The rate constant of proteolysis was decreased by up to three orders of magnitude for the proline mutants depending on the site of the mutation and the protease used. In contrast, substitution by lysine increased the proteolytic resistance by only one order of magnitude characterizing the 'proline concept' as superior to the 'charge concept'. Although the four applied proteases are considered to be unspecific, the degree of stabilization of the ribonuclease molecule varied considerably, indicating the impact of individual differences in their substrate specificity on the proteolytic resistance and degradation pathway of the target protein.

Amino Acid Substitution↗
PubMed1998

Therapists' conceptualization and characterization of the clinical concept of spinal stiffness.

BACKGROUND AND PURPOSE: The clinical concept of spinal stiffness provides one basis for applying spinal manipulation. Because the terms used to describe the perceptual results of manual spinal stiffness testing are poorly defined, the nature and number of attributes contained in the concept remain unclear. This study attempted to clarify the concept of spinal stiffness by examining the relationships among 31 published spinal stiffness descriptors using cluster analysis. SUBJECTS AND METHODS: Each stiffness descriptor was printed on a magnetized rubber strip. Physical therapists in Houston (Tex) and Sydney (New South Wales, Australia) judged the similarity of the stiffness descriptors by arranging them on a board. The squared Euclidean distance between words was calculated, and cluster analysis was performed using Ward's method. RESULTS: Cluster analysis reduced the 31 stiffness descriptors to three superclusters (limited mobility, increased mobility, and viscoelasticity) in both the Houston and Sydney data. CONCLUSION AND DISCUSSION: In a step toward improving the reliability of spinal stiffness judgments, this study has identified the fundamental characteristics of the clinical concept of spinal stiffness. Research is now needed to clearly define these characteristics and then develop protocols that will allow physical therapists to reliably rate these attributes.

Cluster Analysis↗
PubMed1989

The American concept of schizophrenia.

The American concept of schizophrenia is built primarily upon concepts advanced by Kraepelin, Bleuler, and Schneider. Because of the influence of major research studies such as the International Pilot Study of Schizophrenia and the U.S./U.K. study, emphasis has been placed on developing reliable descriptions of symptoms and a precise definition of the disorder. This research also led to a recognition that the American concept of schizophrenia was relatively broad in comparison with that used in the rest of the world. This led to a critical reappraisal of American diagnostic practices during the 1970's, culminating in the narrower definition of schizophrenia in the third edition of the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-III). This definition requires the presence of psychotic features, established chronicity, evidence of deterioration, and the exclusion of affective and "organic" features. In comparison with this definition, the Soviet concept appears to be much broader and to include non-psychotic forms. Treatment implications of these differences are discussed.

Cross-Cultural Comparison↗
PubMed1998

A combined surgical-endovascular device concept for giant aneurysm neck occlusion.

PURPOSE: In this report, we describe a new multimodality device concept for occluding giant aneurysms. The device is designed to exploit the advantages, and avoid the disadvantages, of conventional microneurosurgery and interventional neuroradiology methods. CONCEPT: Our device concept involves surgically placing small permanent magnets, incorporated into a partially occluded magnetic clip, about the extraluminal neck without mechanically compromising the perforating vessels. These magnets serve as optimally positioned anchor points for ferromagnetic materials subsequently introduced via the endovascular route. RATIONALE: Currently, neurosurgical extraluminal obliteration of giant aneurysms is achieved by mechanically closing the aneurysm neck with metal clip blades, which is a technique that risks inadvertent occlusion of critical perforating vessels. Perforating vessel strokes can largely be avoided using endovascular aneurysm occlusion methods. However, in the setting of the giant aneurysm, these endovascular techniques are associated with high rates of incomplete occlusion. DISCUSSION: Preliminary feasibility tests of this concept were conducted using a simple prototype constructed in our laboratories.

Aneurysm↗