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.

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.

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.

Plasma gastrointestinal hormones during spontaneous and induced menstrual cycles.

Plasma levels of secretin, vasoactive intestinal polypeptide (VIP), somatostatin (SRIH), motilin, and/or pancreatic polypeptide, as well as serum estradiol, progesterone, PRL, LH, FSH, and/or GH were measured during the follicular phase, midcycle, and luteal phase of a spontaneous menstrual cycle in eight women and during ovarian stimulation with clomiphene citrate/human menopausal gonadotropin and hCG for in vitro fertilization in nine women. Plasma SRIH concentrations were significantly (P less than 0.02) higher in the luteal phase of spontaneous menstrual cycles than in follicular phase and midcycle. Serum GH levels, however, did not change. Plasma motilin concentrations also were higher in the luteal phase than at mid-cycle (P less than 0.04). Plasma secretin, VIP, and pancreatic polypeptide concentrations did not change during the cycle. Throughout the spontaneous menstrual cycle we found significant positive correlations between plasma SRIH and serum progesterone (P less than 0.007; r = 0.5869), plasma motilin and serum progesterone (P less than 0.02; r = 0.5331), plasma secretin and serum estradiol (P less than 0.04; r = 0.4711), and plasma secretin and serum PRL (P less than 0.02; r = 0.5507). During ovarian stimulation both plasma secretin and VIP gradually increased to a peak on cycle days 0 and 1, respectively (day 0 = the day of hCG injection), whereas plasma SRIH did not change. Serum estradiol and PRL increased significantly, and both peaked on cycle day 1. During ovarian stimulation plasma secretin correlated significantly with serum estradiol (P less than 0.00001; r = 0.9333), serum PRL (P less than 0.03; r = 0.6521), and plasma VIP (P less than 0.03; r = 0.6534). In addition, plasma VIP and serum PRL both correlated significantly with serum estradiol (P less than 0.05; r = 0.6024 and P less than 0.04; r = 0.6384, respectively). These results indicate 1) a possible effect of progesterone on the release of SRIH and motilin during the spontaneous menstrual cycle; 2) the unaltered serum GH concentrations in the luteal phase of the spontaneous menstrual cycle despite elevated plasma SRIH levels are probably due to a stimulatory effect of both progesterone and motilin on GH release; and 3) the increase in plasma secretin and VIP concentrations during ovarian stimulation is probably secondary to the concomitant increase in serum estradiol and/or PRL. We suggest that estradiol and/or PRL beyond a certain threshold level stimulate the release of secretin, and possibly also VIP, into plasma.

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.

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).

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.

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.

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.

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.

Transvaginal sperm intra-fallopian transfer (SIFT). A new treatment for unexplained infertility.

We describe a technique for the blind catheterisation of the fallopian tubes from the vagina using a specially designed device. This procedure was applied to the treatment of ten women with unexplained infertility by transvaginal sperm intrafallopian transfer, and has resulted in four normal ongoing singleton pregnancies.

Precancerous lesions of the cervix uteri in infertile women.

A study of 318 patients with tubal infertility and a control group of 200 unselected infertile women yielded 14 (4.4%) and 1 (0.5%), respectively, with precancerous lesions of the cervix uteri. The one patient in the control group with severe dysplasia was later shown to have tubal infertility. The overall incidence of premalignant lesions of the cervix uteri as reported to the National Cancer Registry of Norway was 0.1% for the age group and period studied. Women with tubal infertility represent a small but comparatively high risk group for the development of precancerous lesions of the cervix uteri.

Pregnancy rates after tubal surgery in different etiological groups of infertility.

An analysis was made of the history of 302 patients who underwent laparotomy for tubal infertility. The following potential risk factors and their relationship to the pregnancy rate and outcome of pregnancy were studied: various groups of gynecological laparotomy, salpingitis, gonorrhoea, complicated and uncomplicated appendicitis, induced and spontaneous abortion and IUD-usage. 234 of the 302 patients (77.5 per cent) had one or more of the potential risk factors in their history. Salpingitis was the most frequent risk factor (36.1 per cent). Regarding pregnancy rate after tubal surgery the most serious risk factor was a previously performed gynecological laparotomy, followed by salpingitis, gonorrhea and complicated appendicitis. We found a gradual decrease in the pregnancy rate with increasing number of risk factors.

Hysterosalpingography in the evaluation of infertility.

Hysterosalpinography (HSG) was performed in 220 women for evaluation of infertility. Laparoscopy or laparotomy for final assessment of tubal patency were carried out in 110. HSG revealed a normal tubal patency in 66.8 per cent, whereas abnormal patency was found in 24.1 per cent. At operation, 85.7 per cent of the HSG diagnoses were confirmed. A clear correlation existed between previous lesions in the genital tract and pathologic findings at HSG and operation. The pregnancy rate following HSG was 15.4 per cent. It is concluded that HSG is of great value in the initial evaluation of infertility. The findings facilitate the decision regarding the final operative procedure: laparoscopy or laparotomy.

Pregnancy rate after diagnostic curettage in the evaluation of infertility.

The Authors present a series of 200 infertile women, who underwent a diagnostic curettage as part of the evaluation of infertility. 18.6 per cent of the patients became pregnant after this procedure after correction for other causes of infertility. Most of the pregnancies were achieved within four cycles after the curettage. From this study, it seems that the removal of a pathological endometrium is not followed by pregnancy. To utilize the therapeutic potential of a diagnostic curettage in infertile women, it is suggested that regularly menstruating women with no history or clinical findings suggestive of tubal disease or endometriosis and without pathological lesions of the endometrium, should wait at least four cycles before the next invasive procedure (HSG or laparoscopy) is performed.

[Surgical treatment of tubal infertility]. / Kirurgisk behandling av tubarinfertilitet.

PIP: A follow-up study of 308 patients operated on for tubal infertility is presented. 119 patients (39%) became pregnant after tubal surgery, resulting in 79 births (26%), 16 spontaneous abortions (5%), and 24 ectopic pregnancies (8%). Gynecological laparotomy had been previously performed on 79 patients; 20% of these achieved term pregnancies, 27 were reoperated after previous tubal surgery, and 11% gave birth to a liveborn infant. 229 patients had their 1st laparotomy because of tubal infertility. This resulted in 30% of full-term pregnancies, 10% ectopic pregnancies, and 5% spontaneous abortions. The best prognosis was after salpingostomy among the unilateral operations (2/3 of the births) and salpingolysis among the bilateral salpingostomies (46% of the births); the poorest prognosis followed bilateral salpingostomy (18% of the births). Most pregnancies occurred within 3 years after tubal surgery. After this time, the possibility of a full-term pregnancy is minimal. (author's modified)^ieng

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.

A new cell culture assay for quality control in IVF.

A new, simple and sensitive bioassay for quality testing in IVF is described. This bioassay (Medi-Cult Hybritest, GEA Ltd, Biotech Division, Hvidovre, Denmark) is based on the culture of the rapidly growing mouse hybridoma cell line 1E6 in a defined serum-free culture medium. The use of serum-free conditions greatly increases the sensitivity to toxic substances, due to the absence of binding proteins. The testing of known toxic agents showed that this assay disclosed cytotoxicity with a high sensitivity. The Hybritest thus provides a simple yet sensitive and reproducible bioassay for quality control of culture media, water, chemical compounds and equipment in an IVF programme. Tests of different batches of culture media showed that media for IVF should be processed from powder and high-quality sterile water. It is important not only to test the single components of the culture media, but also the final product in a sensitive test system.

A characterization of immunoreactive somatostatin in human milk.

In the present work, somatostatin-like immunoreactivity (SLI) in human milk was characterized. In the early postpartum period, SLI levels were highest on the first day after delivery, and then gradually declined. From the fifth day postpartum, SLI levels in milk seemed unchanged. On the fifth day after delivery, milk SLI was significantly (p less than 0.01) higher than plasma SLI (126.3 +/- 11.7 vs. 17.6 +/- 1.1 pmol/L). The results indicate an active transport from blood or synthesis of somatostatin within the mammary gland. Gel filtration studies of skimmed milk, as well as milk exposed to urea and HCl, and aspirated milk from the human premature newborn, revealed that the main portion of milk SLI either represents somatostatin covalently bound to a larger protein, or more likely, a high molecular weight variant of somatostatin.

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.