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.

Fatty acid composition of spermatozoa is associated with BMI and with semen quality.

High body mass index (BMI) is negatively associated with semen quality. In addition, the composition of fatty acids of spermatozoa has been shown to be important for their function. The aim of the study was to examine the association between BMI and the composition of spermatozoa fatty acids in men spanning a broad BMI range. We also analysed the relation between fatty acid composition of spermatozoa and semen characteristics, and the relationship between serum fatty acids and spermatozoa fatty acids. One hundred forty-four men with unknown fertility status were recruited from the general population, from couples with identified female infertility and from morbid obesity centres. Standard semen analysis (WHO) and sperm DNA integrity (DFI) analysis were performed. Fatty acid compositions were assessed by gas chromatography. When adjusted for possible confounders, BMI was negatively associated with levels of sperm docosahexaenoic acid (DHA) (p < 0.001) and palmitic acid (p < 0.001). The amount of sperm DHA correlated positively with total sperm count (r = 0.482), sperm concentration (r = 0.469), sperm vitality (r = 0.354), progressive sperm motility (r = 0.431) and normal sperm morphology (r = 0.265). A negative association was seen between DHA levels and DNA fragmentation index (r = -0.247). Levels of spermatozoa palmitic acid correlated positively with total sperm count (r = 0.227), while levels of linoleic acid correlated negatively (r = -0.254). When adjusted for possible confounders, only the levels of arachidonic acid showed positive correlation between spermatozoa and serum phospholipids (r = 0.262). Changes in the fatty acid composition of spermatozoa could be one of the mechanisms underlying the negative association between BMI and semen quality. The relationship between fatty acids of spermatozoa and serum phospholipids was minor, which indicates that BMI affects fatty acid composition of spermatozoa through regulation of fatty acid metabolism in the testis. The role of dietary intake of fatty acids on the spermatozoa fatty acid composition remains to be elucidated.

Anti-Müllerian hormone in seminal plasma and serum: association with sperm count and sperm motility.

STUDY QUESTION: Is anti-Müllerian hormone (AMH) in seminal plasma and serum associated with sperm count and sperm motility? SUMMARY ANSWER: AMH in seminal plasma is positively associated with sperm concentration, total sperm count, and progressive sperm motility, while no association was found between serum AMH levels and semen characteristics. WHAT IS KNOWN ALREADY: AMH is secreted by the Sertoli cells and is detectable in both serum and seminal plasma in adult men. It has been suggested as a marker of spermatogenesis, however, its function in the adult male is largely unknown. STUDY DESIGN, SIZE, DURATION: Participants were recruited in between 2008 and 2013, from the general population (n = 94) and from couples with female factor infertility in a fertility clinic (n = 32). AMH data were available for 126 participants. PARTICIPANTS/MATERIALS, SETTING, METHODS: Mean age of the participants was 36 years, and BMI was between 19 and 39 kg/m(2). Semen quality was evaluated by semen analysis according to the World Health Organization, and AMH levels were measured in seminal plasma. Blood samples were analyzed for AMH, total testosterone, FSH, LH, and inhibin B. AMH analysis was performed using the improved Beckman Coulter method. MAIN RESULTS AND THE ROLE OF CHANCE: The central 95% intervals of AMH concentrations were 2-2812 pmol/l in seminal plasma and 15-134 pmol/l in serum. Total AMH (pmol/ejaculate) in seminal plasma was positively associated with sperm concentration (B = 0.177, P< 0.001) and total sperm count (B = 0.212, P< 0.001) when adjusted for age, BMI, time of abstinence, and positively associated with progressive sperm motility (B = 6.762, P = 0.001) when adjusted for age, BMI, time of abstinence, and site of sample collection. No association was found between serum AMH and semen characteristics. Serum levels of inhibin B were positively correlated with total AMH in seminal plasma (B = 18.52, P< 0.001) and concentration of AMH in serum (B = 0.507, P< 0.001). LIMITATIONS, REASONS FOR CAUTION: Participants were recruited both from the general population and from a fertility clinic. This may limit the applicability to men in the general population. WIDER IMPLICATIONS OF THE FINDINGS: The AMH levels found in this study show large inter-individual variation, especially in seminal plasma. AMH in seminal plasma may serve as a marker of sperm production, however, in the lower range the predictive value is low. STUDY FUNDING/COMPETING INTERESTS: All funding for this study was received from Oslo and Akershus University College of Applied Sciences. The authors have no conflicts of interest to declare.

Pharmacokinetic interactions between ethanol and heroin: a study on post-mortem cases.

INTRODUCTION: Ethanol and heroin are both depressant drugs on the central nervous system, and combined use is known to be dangerous due to pharmacodynamic interactions, leading to an even higher risk of respiratory depression and death. In addition, previous studies have suggested a pharmacokinetic interaction between ethanol and the metabolism of heroin. The aim of the present study was to investigate if there was a pharmacokinetic interaction between heroin and ethanol, by comparing concentrations of heroin metabolites in cases with and without ethanol, as detected in blood samples collected from a large material of forensic autopsy cases. METHODS: The material consisted of 1583 forensic autopsy cases, all containing 6-monoacetylmorphine (6-MAM), as evidence of heroin intake, in either blood or urine samples, from the time period between the 1st of January 2000 and the 31st of December 2012. Due to the high risk of post-mortem ethanol formation in cases revealing blood ethanol concentrations between 0.1 and 0.3‰, these cases were excluded from the study, along with cases where the analysis for ethanol was missing. After this exclusion of cases, the material (n=1474) was divided into two groups; one group where ethanol was not detected in blood (n=1160), and another group where ethanol was detected in blood at or above the concentration of 0.4‰ (n=314). Furthermore, the material was also divided into two other subgroups; one group where 6-MAM was detected in blood samples, indicating a very recent intake of heroin, and another group where 6-MAM was detected in the urine, but not in blood, indicating a less recent heroin intake. RESULTS: The concentration ratios of morphine/6-MAM, morphine-3-glucuronide (M3G)/morphine, and morphine-6-glucuronide (M6G)/morphine in blood samples, were all significantly lower in the ethanol positive cases compared with that of the ethanol negative cases. For the subgroup of cases revealing a very recent intake of heroin (n=645), only the morphine/6-MAM ratio was significantly lower in the ethanol positive cases than in the ethanol negative cases. For the subgroup of cases with a less recent heroin intake (n=817), lower M3G/morphine and M6G/morphine ratios were found among the ethanol positive cases. CONCLUSIONS: The results indicate that ethanol inhibits two steps in the heroin metabolism; the hydrolysis of 6-MAM to morphine, and the glucuronidation of morphine to M3G and M6G. This pharmacokinetic interaction could further complicate the outcome after combined use of heroin and ethanol, in addition to the already well-known pharmacodynamic interactions.

Variations in testosterone pathway genes and susceptibility to testicular cancer in Norwegian men.

Imbalance between the oestrogen and androgen levels in utero is hypothesized to influence testicular cancer (TC) risk. Thus, variation in genes involved in the action of sex hormones may contribute to variability of an individual's susceptibility to TC. Mutations in testosterone pathway genes may alter the level of testosterone in vivo and hypothetically the risk of developing TC. Luteinizing hormone receptor (LHR), 5α-reductase II (SRD5A2) and androgen receptor (AR) are key elements in androgen action. A case-control study comprising 651 TC cases and 313 controls in a Norwegian population was conducted for investigation of polymorphisms in the LHR, SRD5A and AR genes and their possible association with TC. A statistical significant difference was observed in patients being heterozygous for the LHR Asn312Ser polymorphism when comparing genotypes between all TC cases and controls (OR = 0.66, 95% CI = 0.48-0.89, p(adj) = 0.049). No statistically significant difference between the histological subtypes seminoma and non-seminoma was observed. Our results may suggest a possible association between genetic variation in the LHR gene and the risk of developing TC.

CYP1A1, CYP3A5 and CYP3A7 polymorphisms and testicular cancer susceptibility.

Testicular cancer (TC) incidence is increasing worldwide, but the aetiology remains largely unknown. An unbalanced level of oestrogens and androgens in utero is hypothesized to influence TC risk. Polymorphisms in genes encoding cytochrome P450 (CYP) enzymes involved in metabolism of reproductive hormones, such as CYP1A1, CYP3A5 and CYP3A7, may contribute to variability of an individual's susceptibility to TC. The aim of this case-control study was to investigate possible associations between different CYP genotypes and TC, as well as histological type of TC. The study comprised 652 TC cases and 199 controls of Norwegian Caucasian origin. Genotyping of the CYP1A1*2A (MspI), CYP1A1*2C (I462V), CYP1A1*4 (T461N), CYP3A5*3C (A6986G) and CYP3A7*2 (T409R) polymorphisms was performed using TaqMan allelic discrimination or sequencing. The CYP1A1*2A allele was associated with 44% reduced risk of TC with each polymorphic allele [odds ratio (OR) = 0.56, 95% confidence interval (CI) = 0.40-0.78, p(trend) = 0.001], whereas the CYP1A1*2C allele was associated with 56% reduced risk of TC with each polymorphic allele (OR = 0.44, 95% CI = 0.25-0.75, p(trend) = 0.003). The decreased risk per allele was significant for seminomas (OR = 0.46, 95% CI, 0.31-0.70, p(trend) < 0.001 and OR = 0.31, 95% CI = 0.14-0.66, p(trend) = 0.002, respectively), but only borderline significant for non-seminomas (OR = 0.65, 95% CI = 0.45-0.95, p(trend) = 0.027 and OR = 0.55, 95% CI = 0.30-1.01, p(trend) = 0.052, respectively). There were no statistically significant differences in the distribution of the CYP3A5*3C and CYP3A7*2 polymorphic alleles between TC cases and controls. This study suggests that polymorphisms in the CYP1A1 gene may contribute to variability of individual susceptibility to TC.

Interference with visual memory in rats following infusion of the functional NMDA receptor antagonist, HA-966, into temporal regions.

Results from lesion studies show that selective damage to the temporal cortex or lateral entorhinal cortex impairs visual memory, whereas damage to the hippocampal region does not affect retention of a visual discrimination task. Major input pathways of the above structures use glutamate as neurotransmitter. The glutamate NMDA receptor appears to play an important role for cognitive functions. The objective of the present study was to examine whether microinjections of the functional NMDA receptor antagonist, 3-amino-1-hydroxy-2-pyrrolidinone ((+)-HA-966), might result in effects mimicking those seen in lesion studies. The results show that infusion of HA-966 into the temporal cortex or lateral entorhinal cortex 1.5-3 h after the learning criterion had been obtained led to an impeded visual memory when tested 13 days later, whereas HA-966 infused into the hippocampal region did not affect memory. A similar retention deficit with HA-966 infusions in the temporal cortex or lateral entorhinal cortex was seen when testing took place 23 days later, whereas a markedly weaker effect was observed when the retention period was reduced to 3 days. It is suggested that the hippocampal region is a temporary storing site for nonspatial memory engrams, and later posttraining memory consolidation involves the temporal and lateral entorhinal cortices. Furthermore, the degree of the effect of HA-966 is related to the length of the retention period.

Chronic subcutaneous octreotide decreases gastrointestinal blood loss in blue rubber-bleb nevus syndrome.

BACKGROUND: A patient affected by blue rubber-bleb nevus syndrome had chronic gastrointestinal bleeding requiring weekly blood transfusions. Despite multiple surgical and endoscopic procedures to treat the venous malformations, the patient continued to bleed primarily from lesions in the small bowel. Therefore, this patient was treated with octreotide, a somatostatin analog known to decrease splanchnic blood flow and that is used for acute and chronic gastrointestinal bleeding. METHODS: Octreotide therapy, 5.7 microg/kg subcutaneously twice daily, was initiated, and the patient was followed up clinically. Complete blood counts, blood glucose concentration, pancreatic enzyme concentration, liver function tests, and growth hormone concentration were monitored during treatments. RESULTS: During the 4 weeks after initiation of octreotide therapy, hemoglobin concentration was maintained without the need for transfusions. Octreotide decreased the patient's monthly need for blood transfusion from 52 +/- 7 mL. kg-1. mo-1 of packed red blood cells to 23 +/- 7 mL. kg-1. mo-1. She had no detectable side effects or growth inhibition. Other medical interventions including -epsilonaminocaproic acid, nadolol, and total parenteral nutrition with bowel rest were not as effective as octreotide alone. CONCLUSION: Octreotide decreased the patient's need for blood transfusions. Possible mechanisms include altering blood flow to the gastrointestinal tract and direct effects on the venous malformations.

The ratio of trypsin-2-alpha(1)-antitrypsin to trypsinogen-1 discriminates biliary and alcohol-induced acute pancreatitis.

BACKGROUND: Rapid determination of the etiology of acute pancreatitis (AP) enables institution of appropriate treatment. We evaluated the ability of trypsinogen-1, trypsinogen-2, trypsin-1-alpha(1)-antitrypsin (AAT), and trypsin-2-AAT in serum to identify the etiology of AP. METHODS: The study consisted of 67 consecutive patients with AP admitted to Helsinki University Central Hospital. Forty-two had alcohol-induced AP, 16 had biliary AP, and 9 had unexplained etiology. Serum samples were drawn within 12 h after admission. Trypsinogen-1, trypsinogen-2, trypsin-1-AAT, and trypsin-2-AAT were determined by time-resolved immunofluorometric assays. Logistic regression was used to estimate the ability of the serum analytes to discriminate between alcohol-induced and biliary AP. The validity of the tests was evaluated by ROC curve analysis. RESULTS: Patients with alcohol-induced AP had higher median values of trypsin-1-AAT (P = 0.065), trypsinogen-2 (P = 0.034), and trypsin-2-AAT (P <0.001) than those with biliary AP, who had higher values of amylase (P = 0.002), lipase (P = 0.012), and alanine aminotransferase (P = 0.036). The ratios of trypsin-2-AAT to trypsinogen-1, lipase, or amylase efficiently discriminated between biliary and alcohol-induced AP (areas under ROC curves, 0.92-0.96). CONCLUSIONS: Trypsinogen-2 and trypsin-2-AAT are markedly increased in AP of all etiologies, whereas trypsinogen-1 is increased preferentially in biliary AP. The trypsin-2-AAT/trypsinogen-1 ratio is a promising new marker for discrimination between biliary and alcohol-induced AP.

Rectal prolapse in pediatrics.

Rectal prolapse in pediatrics has its highest incidence in infancy and is uncommonly seen in industrialized countries. The prolapse may involve only the mucosa (mucosal prolapse) or all layers of the rectum (complete prolapse or procidentia). It is usually detected by the child's parents and is brought urgently to medical attention; however, it is usually spontaneously reduced by the time they reach the practitioner's office. Rectal prolapse should be viewed as a symptom of an underlying condition rather than a discrete disease entity. Potential causes are increased intraabdominal pressure, diarrheal and neoplastic diseases, malnutrition, and conditions predisposing to pelvic floor weakness. Its strong association with cystic fibrosis makes the sweat test mandatory for infants and children with recurrent rectal prolapse. Of particular importance are three entities related to rectal prolapse that may easily escape diagnosis by practitioner: occult rectal prolapse, solitary ulcer of the rectum syndrome, and inflammatory cloacogenic polyps. The treatment of rectal prolapse is mainly conservative and is directed at the underlying conditions. Surgical intervention may be required for recurrent rectal prolapse refractory to conservative measures. The simplest, less invasive, yet highly effective approach, appears to be perirectal injection with a sclerosing agent. While the majority of children experience spontaneous resolution of the prolapse, the prognosis is worse when presentation occurs after the age of 4 years.

Effective prophylactic therapy for cyclic vomiting syndrome in children using amitriptyline or cyproheptadine.

OBJECTIVE: To evaluate our experience using the antimigraine prophylactic drugs, amitriptyline and cyproheptadine, for the prophylactic management of cyclic vomiting syndrome (CVS) in children. METHODS AND PATIENTS: Twenty-seven patients (16 males) ranging in age from 2 to 16 years at diagnosis, fulfilling the diagnostic criteria for CVS and treated prophylactically with either amitriptyline (22) or/and cyproheptadine (6) were identified through retrospective chart review. Individual patient data were corroborated by the attending physician and/or interviews with patients and families. Minimum follow-up time before entry into the study group was 5 months. Patients were stratified according to three treatment outcomes: 1) complete response-no attacks, 2) partial response-50% or greater reduction in frequency of attacks, and 3) no response-less than 50% decrease in frequency of attacks. RESULTS: Of the 22 patients treated with amitriptyline, 16 (73%) had a complete response while 4 (18%) had a partial response. Of the 6 patients treated with cyproheptadine, 4 (66%) had a complete response and 1 (17%) had a partial response. Thus, 91% of the amitriptyline group and 83% of the cyproheptadine group had at least a partial response to therapy. No patients experienced significant side effects to either medication. CONCLUSION: The antimigraine prophylactic drugs, amitriptyline and cyproheptadine, represent effective prophylactic agents for the management of CVS in the vast majority of patients fulfilling the diagnostic criteria for this syndrome.

Serum sickness associated with 6-mercaptopurine in a patient with Crohn's disease.

A 43-year-old man with a 19-year history of Crohn's disease experienced serum sickness with acute lobular panniculitis and vasculitis within 2 weeks of initiating 6-mercaptopurine therapy. He had no history of extraintestinal manifestations of Crohn's disease or drug allergy. Symptoms included disabling joint pain, proteinuria, fever, rash, and malaise. To our knowledge, this adverse drug reaction has not been described in association with 6-mercaptopurine.

Recognition and treatment of venous malformations of the rectum.

Venous malformations of the rectum are uncommon lesions that present complex management problems (1-6). The vast majority of these lesions present with rectal bleeding in infancy or childhood. Many cases have been treated as colitis for years before the correct diagnosis was made. The correct diagnosis has generally been based on gross appearance, confirmed subsequently by plain radiographs and angiography. Heroic surgical intervention has been the only repeatedly reported "cure" in the literature. One patient has been reported who did well for 20 years with sclerosis of the hemorrhoidal vein at surgery followed by intermittent transrectal sclerotherapy (7,8). Another patient would appear to have had longterm success with radiation therapy (9-11). We report four new cases of venous malformations of the rectum and results to date of a new therapeutic option with transcutaneous ethanol sclerotherapy in two of these patients. A discussion of alternate methods of treatment is included.

Platelet alpha-2 adrenoreceptor activity pre-treatment and post-treatment in major depressive disorder with melancholia.

Changes in alpha-2 adrenoreceptor density and affinity during antidepressant treatment were studied using 3H-yohimbine binding to human platelet membranes. Baseline measurements were conducted in 21 patients diagnosed as having major depressive disorder with melancholia, and an equal number of age and sex matched normal controls. No differences were observed in receptor density or binding between pre-treatment subject groups and normal matched controls. Subjects participated for 6 weeks in a trial of placebo, adinazolam, or amitriptyline. Alpha-2 adrenoreceptor binding was not significantly changed from baseline following antidepressant treatment.

Surgical management of gastroesophageal reflux in severely mentally retarded children.

Thirty-three severely mentally retarded children with profound malnutrition and aspiration pneumonitis were treated by gastrostomy and Nissen fundoplication. Early and late complications were 27.3% and 16.6% respectively. Mortality was 9.4%. All surviving patients gained weight. Time required for feeding was greatly reduced. This study supports earlier operative intervention for the mentally retarded child with gastroesophageal reflux, malnutrition and aspiration pneumonitis.

Psychotropic medication and nonfatal cafe coronary.

Obstructive asphyxia, also known as cafe coronary, has been linked to both medicated and nonmedicated psychiatric patients. An 18-month prospective audit of choking patients was conducted in a psychiatric hospital. Based upon all medications received in the 5 days preceding the event, mean daily chlorpromazine and atropine equivalent dosages were also calculated for age, sex, and diagnosis matched controls based upon all medications received during their entire hospital stay. Paired t-tests showed no significant differences between choking patients and their matched controls except that greater mean daily chlorpromazine equivalents were present in the severe choking subgroup. Computation of log odds of choking risk increases with interaction of increased mean doses of each drug type and age, and also with interaction of increased chlorpromazine equivalents and increased atropine equivalents. Patients receiving high dosages of drug(s) with antidopaminergic or anticholinergic activity are at greater risk of choking and should be monitored closely.