Artificial intelligence in the fertility clinic: status, pitfalls and possibilities.

In recent years, the amount of data produced in the field of ART has increased exponentially. The diversity of data is large, ranging from videos to tabular data. At the same time, artificial intelligence (AI) is progressively used in medical practice and may become a promising tool to improve success rates with ART. AI models may compensate for the lack of objectivity in several critical procedures in fertility clinics, especially embryo and sperm assessments. Various models have been developed, and even though several of them show promising performance, there are still many challenges to overcome. In this review, we present recent research on AI in the context of ART. We discuss the strengths and weaknesses of the presented methods, especially regarding clinical relevance. We also address the pitfalls hampering successful use of AI in the clinic and discuss future possibilities and important aspects to make AI truly useful for ART.

Combining a weed traits database with a population dynamics model predicts shifts in weed communities.

A functional approach to predicting shifts in weed floras in response to management or environmental change requires the combination of data on weed traits with analytical frameworks that capture the filtering effect of selection pressures on traits. A weed traits database (WTDB) was designed, populated and analysed, initially using data for 19 common European weeds, to begin to consolidate trait data in a single repository. The initial choice of traits was driven by the requirements of empirical models of weed population dynamics to identify correlations between traits and model parameters. These relationships were used to build a generic model, operating at the level of functional traits, to simulate the impact of increasing herbicide and fertiliser use on virtual weeds along gradients of seed weight and maximum height. The model generated 'fitness contours' (defined as population growth rates) within this trait space in different scenarios, onto which two sets of weed species, defined as common or declining in the UK, were mapped. The effect of increasing inputs on the weed flora was successfully simulated; 77% of common species were predicted to have stable or increasing populations under high fertiliser and herbicide use, in contrast with only 29% of the species that have declined. Future development of the WTDB will aim to increase the number of species covered, incorporate a wider range of traits and analyse intraspecific variability under contrasting management and environments.

Duration and spread of an entomopathogenic fungus, Beauveria bassiana (Deuteromycota: Hyphomycetes), used to treat varroa mites (Acari: Varroidae) in honey bee (Hymenoptera: Apidae) hives.

A strain of the fungus Beauveria bassiana (Balsamo) Vuillemin (Deuteromycota: Hyphomycetes) isolated from varroa mites, Varroa destructor Anderson & Trueman (Acari: Varroidae), was used to treat honey bees, Apis mellifera L. (Hymenoptera: Apidae), against varroa mites in southern France. Fungal treatment caused a significant increase in the percentage of infected varroa mites compared with control treatments in two field experiments. In the first experiment, hives were treated with a formulation containing 0.37 g of B. bassiana conidia per hive and in the second experiment with a dose of 1.0 g of conidia per hive. The percentage of infected varroa mites also increased in the nontreated (control) hives, suggesting a movement of conidia, probably via bee drift, among the hives. Mite fall was significantly higher among treated hives compared with control hives on the sixth and eighth days after treatment in the first experiment. These days correspond to previously published data on the median survivorship of mites exposed to that fungal solate. The interaction of treatment and date was significant in the second experiment with respect to mite fall. Increases in colony-forming unit (cfu) density per bee were observed in all treatments but were significantly higher among bees from treated hives than control hives for at least a week after treatment. The relationship between cfu density per bee and proportion infected was modeled using a sigmoid curve. High levels of infection (>80%) were observed for cfu density per bee as low as 5 x 102 per bee, but the cfu density in hives treated with 0.37 g generally dropped below this level less than a week after treatment.

Pest management in traditional maize stores in West Africa: a farmer's perspective.

Farmers in the Republic of Benin have few resources to invest in protection of stored maize, and prophylactic pesticide application is often recommended by extension and development agencies. Neither the efficacy nor profitability of such an application in traditional maize storage facilities has been addressed quantitatively. In this study, existing management options for stored maize were evaluated monthly over 6 mo in central and southern Benin with respect to their effects on grain injury and on densities of Prostephanus truncatus (Horn) and Sitophilus zeamais Motschulsky. P. truncatus infested 54% of the experimental stores in the study even though Teretrius nigrescens (Lewis), a natural enemy introduced against P. truncatus, was well established in the region. S. zeamais was the most common pest, found in 85% of the experimental storage facilities. Prophylactically treated maize was, on average, worth more than untreated maize for month 1 through 5 in southern Benin, after taking into account market price, pesticide costs, percentage grain damage and weight loss, but maize storage was not profitable overall. No difference was observed between treatments in central Benin. After 6 mo treated storage facilities were not significantly different from untreated storage facilities in terms of either percentage damage or profit in either region. A rapid scouting plan intended to provide farmers with a means for identifying storage facilities at greatest risk of severe P. truncatus infestation was field validated. Given that unsafe pesticide use is prevalent in Benin, research and extension services should clearly state the limitations to prophylactic treatment and increase the effort to educate farmers on appropriate pesticide use, store monitoring and marketing.

The Effects of an entomopathogenic fungus, Beauveria bassiana (balsamo) vuillemin (hyphomycetes), on Prostephanus truncatus (horn) (Col.: Bostrichidae), Sitophilus zeamais motschulsky (Col.: Curculionidae), and grain losses in stored maize in the Benin Republic.

A fungal entomopathogen, Beauveria bassiana, was used to treat maize ears placed in traditional grain stores against Prostephanus truncatus in a field experiment conducted from September 1997 to March 1998 in the Benin Republic, West Africa. Treatments included oil-based spray with and without conidia, maize stored with and without the husk, and stores with and without artificial infestation. Additional treated ears kept in insect-proof cages under field conditions were sampled weekly and exposed to insects to estimate the virulence and persistence of the pathogen during the storage season. P. truncatus densities were significantly lower in treatments that included conidia, although densities were high in all artificially infested treatments and grain losses were severe. The effect of the pathogen was modeled with an exponential decay function and incorporated in a published P. truncatus simulation model. The effects of hypothetical pathogens with different virulence and persistence characteristics were evaluated in terms of insect density and percentage grain loss.

Grain injury models for Prostephanus truncatus (Coleoptera: Bostrichidae) and Sitophilus zeamais (Coleoptera: Curculionidae) in rural maize stores in West Africa.

Prostephanus truncatus (Horn) and Sitophilus zeamais Motschulsky have been reported as the two most serious pests of stored maize in sub-Saharan Africa and smallholder farmers are in urgent need of guidelines for their proper management. In this article we investigate the injury rates attributable to these two species in terms of percentage weight loss and percentage grain damage, and we derive functional response models for the two species on maize. The models successfully described the progression of grain injury in an extensive data set compiled from previously published studies, comprising 46 time series of data relating maize injury and insect pest density. The grain injury models can be used in conjunction with predictive models of pest population dynamics to guide the development of integrated management strategies for postharvest maize pests in West Africa and comparable regions elsewhere.

CD34+ selection of autologous peripheral blood stem cells for transplantation following sequential cycles of high-dose therapy and mobilization in multiple myeloma.

A potential problem of autologous transplantation in the treatment of multiple myeloma (MM) is the infusion of tumor cells. CD34+ selection has been used to purge autografts in MM and it is also possible to reduce tumour cell contamination of autografts by cytotoxic drug therapy prior to peripheral blood stem cell (PBSC) collection. To evaluate the effectiveness of a protocol combining multiple cycles of high-dose therapy and CD34+ selection to reduce tumour contamination of PBSC autografts, 34 MM patients were entered on a treatment schedule comprising two sequential cycles of mobilisation, CD34+ selection, and transplantation following high-dose therapy. In the second cycle of mobilisation there was a five-fold reduction in tumour contamination of the stem cell harvest (0.5 x 106/kg) compared with the first cycle (2.5 x 106/kg). In the 97 CD34+ selection procedures performed a median of 185 x 108 mononuclear cells (MNC) were processed yielding a median of 0.98 x 108 CD34+-enriched cells. CD34+ cells were enriched 68-fold from 1. 3% to 88.6%. The median yield of CD34+ cells was 42.2%. Following CD34+ selection the tumour cell contamination of the leukapheresis product was reduced by a median of 2.7 logs. This study demonstrates that in multiple myeloma a significant reduction in the malignant contamination of stem cell autografts can be achieved by combining the in vivo purging effect of cytotoxic therapy with in vitro purging by CD34+ selection.

Evaluation of sequential sampling plans for the larger grain borer (Coleoptera: Bostrichidae) and the maize weevil (Coleoptera: Curculionidae) and of visual grain assessment in West Africa.

Repeated sampling of rural maize stores in Benin was conducted to evaluate published parameters of a sequential sampling plan for a negative binomial distribution to determine pest status for Prostephanus truncatus (Horn) and Sitophilus zeamais Motschulsky. A computer program was used to rerandomize the data and evaluate the effects, in terms of average sample number and error rates, of different sampling plan parameter values. With respect to P. truncatus, lower and upper thresholds of 0.2 and 1.0 insects per ear and parameter values of k = 0.2 and alpha = beta = 0.1 were found to be adequate. With respect to S. zeamais, lower and upper thresholds of 10 and 20 insects per ear and parameter values of k = 1.0 and i alpha = beta = 0.1 were found to be adequate. Simplified sampling rules were proposed in which 11 ears should be sampled and if no P. truncatus are found, the population is low; otherwise the Wald plan should be followed. Owing to the lower per capita rate of damage, effective simplified sampling rules for S. zeamais were difficult to construct. An evaluation of the visual assessment scale rising whole ears showed that a visual scale estimating percentage damage rather than percentage loss, might be easy to construct and preferable for traders. Further work is needed to improve the usefulness of the visual scale in pest management decision support.

Regulation of insulin-like growth factor-binding protein-1 and progesterone secretion from human granulosa-luteal cells: effects of octreotide and insulin.

OBJECTIVE: To examine the effects of the synthetic somatostatin-analogue octreotide and human recombinant insulin on the release of insulin-like growth factor binding protein-1 (IGFBP-1) and P from human granulosa-luteal cells. DESIGN: Primary culture of human granulosa-luteal cells. SETTING: Academic research laboratory. PATIENT(S): Women undergoing oocyte retrieval for IVF-ET because of tubal infertility. INTERVENTION(S): Octreotide or insulin were added to the cultures; sampling of culture medium was performed after 48 hours. MAIN OUTCOME MEASURE(S): Insulin-like growth factor binding protein-1 and P. RESULT(S): Octreotide significantly inhibited IGFBP-1 (58.8% compared with controls) and P release (66.1% compared with controls). Insulin abolished IGFBP-1 release while stimulating P release (200.7% compared with controls). There was a significant and positive correlation between IGFBP-1 and P levels. CONCLUSION(S): Octreotide and insulin have a significant effect on human granulosa-luteal cell function in terms of IGFBP-1 and P release. Our results suggest a local ovarian mechanism for the recently observed effects of octreotide in the treatment of women with polycystic ovary syndrome.

Somatostatin in physiological concentrations inhibits basal and enhances luteinizing hormone-stimulated progesterone release from human granulosa-luteal cells.

To study the effect of somatostatin on ovarian function, we investigated the action of physiological concentrations of somatostatin (5.0 x 10(-12)-1.0 x 10(-10) M) on the basal and luteinizing hormone (LH)-stimulated progesterone release from cultured human granulosa-luteal cells obtained from in-vitro fertilization patients. Somatostatin exerted a significant and inhibitory effect on basal progesterone release from the granulosa-luteal cells, whereas it was unable to inhibit LH-stimulated progesterone release. Instead, a significant increase in progesterone release was observed after concomitant incubation with LH and somatostatin compared with the untreated controls. We suggest that somatostatin may serve as a regulator of ovarian functions under physiological conditions.

Somatostatin in human follicular fluid.

To demonstrate the presence of somatostatin in human pre-ovulatory follicular fluid, and to assess the role of this peptide in follicular maturation, a total of 66 follicular fluid samples were obtained from 26 patients at the time of oocyte recovery for in-vitro fertilization. Follicular fluid concentrations of somatostatin, oestradiol, progesterone and androstenedione were measured by immunoassay. Somatostatin concentrations in concomitantly obtained plasma samples were also analysed. Follicular fluid somatostatin concentrations ranged from undetectable (< 1.5 pmol/l) to 109.4 pmol/l. The mean +/- SE somatostatin concentrations in follicular fluid (12.8 +/- 1.8 pmol/l) were significantly (P < 0.0001) increased compared to corresponding plasma concentrations of somatostatin (6.5 +/- 0.2 pmol/l). A significant and positive correlation existed between follicular fluid and plasma somatostatin concentrations (r = 0.27; P < 0.03). No differences in either follicular fluid or plasma somatostatin concentrations were found between different stimulation protocols or diagnostic groups. Neither did follicular fluid somatostatin concentration vary with follicular size. Similarly, no differences in somatostatin concentrations were found between follicular fluids associated with fertilized (13.2 +/- 2.1 pmol/l) or non-fertilized oocytes (10.5 +/- 1.6 pmol/l). Follicular fluid concentrations of somatostatin correlated positively with those of progesterone (r = 0.30; P = < 0.04), but not with those of oestradiol or androstenedione or with the androstenedione/oestradiol ratio. The relationship between follicular fluid somatostatin and progesterone concentrations suggests that follicular fluid somatostatin may have a physiological role in follicular maturation and the luteinization process.

Effects of ovarian stimulation on blood pressure and plasma catecholamine levels.

Effects of ovarian stimulation for in vitro fertilization on blood pressure and plasma catecholamine levels were studied in 10 women. The examinations were carried out before hormonal treatment with human menopausal gonadotropin (day three of the menstrual cycle, mean serum oestradiol concentration 0.2 nmol l-1, and on the day after ovulation induction with human chorionic gonadotropin (cycle days 10-12, mean serum oestradiol concentration 7.4 nmol l-1). Systolic and diastolic blood pressures (mean +/- SD) decreased 6.7 +/- 8.6 mm Hg, p = 0.049, and 5.3 +/- 4.7 mm Hg, p = 0.009, respectively), and venous plasma noradrenaline increased (42 +/- 44 pg ml-1, p = 0.02) during ovarian stimulation. No significant change was observed in either arterial noradrenaline, arterial adrenaline or venous adrenaline. After stimulation a positive correlation was observed between systolic blood pressure and arterial adrenaline (r = 0.73, p = 0.027), and between systolic blood pressure and the arterial-venous difference for adrenaline (r = 0.81, p = 0.007). The increased venous noradrenaline levels may be a reflex-mediated activation of the sympathetic nervous tone due to a decrease in blood pressure, or may indicate reduced neuronal re-uptake of released noradrenaline. The mechanisms behind the strong correlation between adrenaline and blood pressure are unclear, but may be induced by the supraphysiological oestradiol levels. Thus, adrenaline seems to be more important for blood pressure control in this particular setting.

Plasma concentrations of motilin and somatostatin are increased in late pregnancy and postpartum.

OBJECTIVE: To examine plasma levels of motilin and somatostatin throughout pregnancy. DESIGN: Prospective observational study. SETTING: University Hospital, Norway. SUBJECTS: Eight healthy pregnant women (aged 24-38 years) six of them primigravidae and eight healthy non-pregnant women of similar age with ovulatory menstrual cycles. INTERVENTIONS: In the pregnant women blood samples were obtained at 4-week intervals from 8 weeks gestation throughout pregnancy and again at 5 days and 28 days postpartum. In the non-pregnant controls blood samples were obtained on cycle days 4, 7, 10, 13, 14, 15, 18, 21 and 24. MAIN OUTCOME MEASURES: Plasma levels of motilin and somatostatin. RESULTS: Plasma concentrations of both motilin and somatostatin rose continuously during pregnancy, and motilin levels increased still further to a peak of 165.1 (SE 35.8) pmol/l at 5 days postpartum. Plasma motilin levels were significantly higher during the third trimester and at 5 days postpartum compared with non-pregnant controls (P less than 0.0001). The highest plasma somatostatin levels were found at 40 weeks gestation and at 5 days postpartum (mean 32.1 SE 1.1 pmol/l). Somatostatin levels were significantly higher during the second and third trimester and the postpartum period compared with levels in the follicular phase of the non-pregnant controls (P less than 0.0001). CONCLUSIONS: Circulating levels of motilin cannot play a major role in the relaxation of the gut in pregnancy, but somatostatin may play a part in regulating motility.

Medium-associated luteinization expressed as progesterone release in granulosa-luteal cells isolated from patients undergoing in-vitro fertilization.

The present study describes the effect of culture medium components on progesterone release from human granulosa-luteal cells isolated from patients undergoing in-vitro fertilization (IVF). Progesterone release was selectively measured as a central parameter of in-vitro luteinization, a process believed to decrease the success rate of IVF treatments. Ten different media of relevance to embryo culture were investigated for their effect on progesterone release in unstimulated granulosa cell cultures and in cultures stimulated with human chorionic gonadotrophin (HCG) (1 IU/ml) during 4 days in vitro. Culture media supplemented with human serum yielded the greatest secretion of progesterone. Supplementation with fetal calf serum caused an intermediate pattern of progesterone release. Substitution of serum with a synthetic replacement (Medi-CultR SSR 1 and 2), lacking hormones, cholesterol and growth factors, led to a minimal output of progesterone from granulosa-luteal cells. Complex media (RPMI 1640 and Ham's F10) generally caused a greater progesterone release than simple salt solution (EBSS). No effect of insulin was detected when added to serum-free media.

Increased plasma levels of vasoactive intestinal polypeptide in pre-eclampsia.

OBJECTIVE: To investigate the plasma vasoactive peptide (VIP) levels in pregnancies complicated by pre-eclampsia. DESIGN: A prospective clinical study. SETTING: University Department of Obstetrics, Tromsø, Norway. SUBJECTS: 18 women with untreated gestational proteinuric hypertension between 32 and 40 weeks gestation (13 primigravid) and 8 women with normal pregnancies of similar gestational age. INTERVENTIONS: Fasting blood samples on two occasions, 10 min apart. MAIN OUTCOME MEASURES: Plasma VIP measured by radioimmunoassay. RESULTS: Mean maternal plasma VIP was 13.9 (SEM 1.7) pmol/l in those with pre-eclampsia and 4.4 (SEM 0.5) pmol/l in normal pregnancies (P less than 0.0001). CONCLUSION: The increased levels of VIP in pre-eclampsia may represent a powerful compensatory mechanism to restore vascular perfusion of various organs, including the uterus and placenta.

Does ovarian stimulation for in-vitro fertilization induce a hypercoagulable state?

Effects on blood coagulation and fibrinolytic activity during ovarian stimulation for in-vitro fertilization (IVF) were examined in 12 women. Blood samples were taken prior to hormonal stimulation (days 2-3 of the menstrual cycle, mean serum oestradiol concentration 0.16 nmol/l) and the day after ovulation induction with human chorionic gonadotrophin (HCG) (days 10-12, mean serum oestradiol concentration 5.35 nmol/l). We measured whole blood clotting time, whole blood clot lysis time, plasma fibrinogen, factor VII and antithrombin III. The whole blood clotting time was slightly, but not significantly shortened after ovarian stimulation. A significant rise in plasma fibrinogen (P less than 0.001) and reduction in antithrombin III (P less than 0.001) were observed, whereas no change in factor VII was found. The blood fibrinolytic activity was significantly reduced as evaluated by an increase in the clot lysis time (P less than 0.02). These results indicate that ovarian stimulation for IVF may create a state of hypercoagulability.

[Determination of intact parathyroid hormone in patients with calcium metabolism disorders]. / Måling av intakt parathormon hos pasienter med kalsiumforstyrrelser.

We have used an immunoradiometric assay (IRMA) to measure intact PTH. The serum-levels of PTH followed a log-normal distribution in a population of 85 healthy post-menopausal women, with a geometric mean of 1.9 pmol/l and a range of 0.8-6.1 pmol/l. The correlation between measurements performed using the IRMA and a radioimmunoassay which measured the C-terminal portion of the PTH molecule was 0.85. It was only the IRMA, however, that could measure subnormal values. Two of 27 patients with primary hyperparathyroidism had PTH-values in the upper reference interval. The rest of the patients had elevated levels. Patients with hypercalcemia due to malignancy had subnormal or low normal (less than 2.5 pmol/l) PTH values. Half of the patients with hypoparathyroidism had PTH below the limit of detection. Four subjects with familial hypercalciuric hypercalcemia had normal (3) or slightly elevated PTH-levels.

Handling of tubal infertility after introduction of in vitro fertilization: changes and consequences.

This study aimed at quantifying some important social and economic consequences of the altered handling of tubal infertility after the establishment of IVF treatment. The number of tubal operations was reduced by 50%. This had most important and positive implications on the availability of the operating theater for other elective operations, on the availability of hospital beds for other patient groups, and on the total duration of the certificate of illness. The calculated costs per live birth were $17,000 after tubal surgery, compared with $12,000 after IVF treatment. Life table analyses demonstrated a highly significant increased rate of deliveries after a complete IVF treatment (72.3% per patient) compared with tubal surgery (23.7%, P less than 0.001).

Experience with GnRH agonists in an in vitro fertilization (IVF) program.

The experience using pre-treatment with GnRH-agonists in an IVF-program are reported. 55 patients having a 'poor response', premature LH surge, or follicular luteinization in previous treatment cycles were treated for a total of 68 cycles. Therapy with GnRH agonists was initiated in the midluteal phase, and given by self-administration subcutaneously. Stimulation started with exogenous gonadotropins on a fixed day (Saturday) after pituitary desensitization had first been obtained, and resulted in all follicular punctures being performed on weekdays. Five treatment cycles (7.4%) were cancelled because of 'poor response'. Where the indication for GnRH-agonist therapy was previous 'poor response', a cancellation rate of 36.4% was observed, whereas a cancellation rate of only 1.8% was found in the other indication groups (p less than 0.001). Altogether 26 clinical pregnancies were achieved, five of these ending in a spontaneous abortion. The rate of deliveries was 33% per oocyte retrieval, and 40% per pre-embryo replacement.

Prolactin response to secretin during the spontaneous menstrual cycle in women.

The effect of an intravenous infusion of secretin (2.0 CU/kg/h) on serum prolactin (PRL) and estradiol levels and plasma levels of vasoactive intestinal polypeptide and somatostatin (SRIH) was studied in 8 healthy and normally cycling women during the midfollicular phase (cycle day 7), at midcycle (day 14), and during the midluteal phase (day 21) of the menstrual cycle. When compared to basal preinfusion levels, a significant decrease in serum PRL levels was observed at steady state concentrations of plasma secretion (+30 to +60 min) both during the follicular (p less than 0.03) and the luteal (p less than 0.0001) phases. At midcycle a nonsignificant decrease was observed. A significant and negative correlation existed between serum PRL and plasma secretin levels in the follicular phase (r = -0.33; p less than 0.05) and in the luteal phase (r = 0.73; p less than 0.0001). The plasma concentrations of SRIH increased significantly at steady state conditions of secretin at midcycle (p less than 0.02) and in the luteal phase (p less than 0.04), while no effect was found during the follicular phase. A significant and positive correlation between plasma levels of SRIH and secretin was observed at midcycle (r = 0.63; p less than 0.002) and in the luteal phase (r = 0.46; p less than 0.02). No effect of secretin on plasma vasoactive intestinal polypeptide and serum estradiol concentrations was demonstrated. These results suggest that the suppression of PRL in the follicular phase of the spontaneous menstrual cycle can be ascribed to an effect of secretin alone.(ABSTRACT TRUNCATED AT 250 WORDS)