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ACUTE SEVERE HYPOPHOSPHATAEMIA MIMICKING WERNICKE'S ENCEPHALOPATHY
44 DELAYED EXPULSION OF TRANSFER FLUID AFTER IVF/ET
SIR,-One impediment to in-vitro fertilisation (IVF) has been the success rate in establishing pregnancy after embryo transfer (ET) into the uterus via a transcervical catheter. Pregnancy rates are only 20-3007o per transfer in the world’s best IVF centres. Our low
observations suggest that part at least of the failed transfers may be accounted for by delayed expulsion of embryos from the uterine cavity. All embryos were obtained after IVF of oocytes obtained by the transvaginal ultrasound-guided method. We did the simple experiment of leaving the vaginal speculum in place for 15 min after ET and observing whether or not liquid was expelled during this time. Transfers were done with a blunt-tipped, side-hole catheter of type used in many IVF programmes; the transfer volume was usually 50-100 1. Patients were usually in the dorsal lithotomy position. To our surprise, we frequently observed forceful expulsion of the transfer fluid droplet 5-10 min after the transfer. This seemed to be due to contraction of the uterus in response to mechanical stimulation, although the patient rarely felt contractions. Delayed expulsion was observed after 7 transfers in 32 patients (22%). 5 of these patients became pregnant (16%). The mean number of embryos per transfer was 1 - 7. A subsequent series of 28 patients was pretreated with 550 mg naproxen given orally 2 h before transfer, and another 275-550 mg was given 30 min before transfer. Leakage was noted in 5 women (18%), but the volume expelled seemed smaller and the expulsion less forceful than it had been in the untreated series of patients. 8 women became pregnant (29%) after naproxen pretreatment. The mean number of embryos per transfer was 1-7, as before. The difference in pregnancy rates between the two series is not significant (p=0-2) and no firm conclusion about the possible efficacy of naproxen can be drawn. However, our results are consistent with other evidence, not supported by direct observation, that expulsion of embryos may contribute to IVF pregnancy failure. For example, Meldrum and associatesI have reported an improvement in pregnancy rates from 16% to 32% when the volume of fluid and air in which embryos were transferred was reduced. Our observation that delayed expulsion of transfer fluid after embryo replacement is common in human IVF cycles should provide a stimulus for careful analysis of methods for its reduction or elimination. of Obstetrics &
Department Gynecology, Fairfax Hospital, Fairfax, Virginia 22031, USA; and Medical College of Virginia 1 Meldrum on in
JOSEPH D. SCHULMAN
D, Steingold KA, de Ziegler D, et al. Presented at Fourth World Conference
Vitro Fertilization
(Melbourne, November 1985), abstr
Wernicke’s encephalopathy, his neurological condition deteriorated and he was referred to our hospital. On admission he was sleepy, displayed moderate hypoventilation, and could not raise his legs. Arterial blood gas measurements were: pH 7-41, pCO2 47-6 mm Hg, p02 45 mm Hg, and actual bicarbonate 29 - 6 mmol/1. Continuation of the supplements did not prove helpful. 2 days later further blood tests revealed severe hypophosphataemia (0-21 mmol/l; normal 0-85-1-40). He was given oral potassium phosphate and the sleepiness and weakness disappeared in a few hours, making a causal relation between the hypophosphataemia and the neurological disorders highly probable. 2 days later electromyography disclosed only moderate
polyneuropathy. This patient’s neurological signs and symptoms were logically interpreted as consistent with Wernicke’s encephalopathy. However, alcoholism, alcohol withdrawal, and respiratory insufficiency also known to contribute to acute severe hypophosphataemia 1-5 and the symptoms related to hypophosphataemia closely resemble the signs of Wernicke’s encephalopathy, including somnolence, confusion, gaze paresis, limb ataxia, muscular weakness, and areflexia. 1-3 Thus the diagnosis of acute severe hypophosphataemia may easily be missed, accounts of it being so sparse in neurological texts. Although acute severe hypophosphataemia is commonly seen as a complication of hyper alimentation, 6 NewmanS found that even oral alimentation may precipitate hypophosphataemia-related acute paralysis in malnourished phosphorus-depleted alcoholics. This was confirmed in our patient, whose severe weakness was probably due to decreased concentration of adenosine triphosphate in skeletal muscles;’his normal serum creatine kinase activity (46 IU/1) excluded rhabdomyolysis.7 Serum phosphorus should be measured in all alcoholics who present with symptoms suggesting Wernicke’s encephalopathy, especially when thiamine supplementation does not result in clinical improvement. Neurological textbooks should mention this condition in lists of electrolyte disturbances associated with neurological disorders. are
Department of Neurology, St Lucas Ziekenhuis, 1061 AE Amsterdam, Netherlands
J. VANNESTE
J. HAGE
1 Layzer RB Disorders of phosphorus metabolism. In: Neuromuscular manifestations of systemic disease. Philadelphia: FA Davis, 1985: 67-77. 2. Lotz M, Zisman E, Bartter FC. Evidence for a phosphorus-depletion syndrome in man N Eng J Med 1968; 278: 409-15. 3. Knochel JP The pathophysiology and clinical characteristics of severe hypophosphatemia Arch Intern Med 1977; 137: 203-20. 4. Territo MC, Tanaka KR Hypophosphatemia in chronic alcoholism. Arch Intern Med
82.
1973; 5 Newman
134: 445-47.
JH, Neff TA, Ziporin
P. Acute respiratory failure associated with 1101-03. 6. Silvis SE, Paragas PD. Paresthesias, weakness, seizures and hypophosphatemia in patients receiving hyperalimentation. Gastroenterology 1972; 62: 513-20 7. Knochel JP, Bilbrey GL, Fuller TJ, et al. The muscle cell in chronic alcoholism: the possible role of phosphate depletion in alcoholic myopathy Ann NY Accad Sci 1975; 252: 274-86.
hypophosphatemia N Engl J Med 1977; 296:
ACUTE SEVERE HYPOPHOSPHATAEMIA MIMICKING WERNICKE’S ENCEPHALOPATHY
SIR,-Neurological textbooks, with one exception,’ do not mention acute severe hypophosphataemia as a potential cause of neurological disorders. This blind spot may lead to a diagnostic delay, especially when the clinical features suggest a much more familiar neurological syndrome such as Wernicke’s encephalopathy. A 56-year-old alcoholic was admitted to another hospital because of increasing apathy, generalised muscular weakness, and fever. He malnourished man with a temperature of 39-8°C, a blood pressure of 90/60 mm Hg, and signs of lobar pneumonia. Abnormal neurological findings consisted of disorientation, hallucinations, tremor, gaze paresis, respiratory weakness, severe paresis of the legs, paraesthesiae, and areflexia. The erythrocyte sedimentation rate was 110 mm/h, liver enzymes were moderately increased, and there was hypokalaemia (2 - 5 mmol/1). Serum thiamine concentration and transketolase activity were not measured. He was treated with amoxycillin, haloperidol, supplementation with potassium, magnesium, and vitamins, and oxygen. Normal food intake was still possible. Despite this treatment for a presumptive diagnosis of early delirium tremens and
was a
AMOUNTS OF FEVERFEW IN COMMERCIAL PREPARATIONS OF THE HERB
SIR,-Extracts of feverfew (Tanacetum parthenium) inhibit secretory
activity
in blood
platelets
and
polymorphonuclear
leucocytes,and these effects in vitro may be relevant to any clinical effects of the herb. In the double-blind trial in migrainefeverfew supplied in specially prepared capsules. In view of the possible benefits of feverfew we need to know the activity of commercial preparations. Using an assay based on inhibition of secretory activity in platelets we have analysed some commercial preparations and compared the results with those obtained using air-dried leaves taken from feverfew plants grown in the Department of Botany, University of Nottingham. Chloroform extracts of leaves, tablets, and drops were filtered and dried under nitrogen. The residues were dissolved in phosphate buffered saline, pH 7 - 4, and then tested for their capacity to inhibit release of 14 C-serotonin from pre-labelled platelets in platelet-rich was
SIR,-One impediment to in-vitro fertilisation (IVF) has been the success rate in establishing pregnancy after embryo transfer (ET) into the uterus via a transcervical catheter. Pregnancy rates are only 20-3007o per transfer in the world’s best IVF centres. Our low
observations suggest that part at least of the failed transfers may be accounted for by delayed expulsion of embryos from the uterine cavity. All embryos were obtained after IVF of oocytes obtained by the transvaginal ultrasound-guided method. We did the simple experiment of leaving the vaginal speculum in place for 15 min after ET and observing whether or not liquid was expelled during this time. Transfers were done with a blunt-tipped, side-hole catheter of type used in many IVF programmes; the transfer volume was usually 50-100 1. Patients were usually in the dorsal lithotomy position. To our surprise, we frequently observed forceful expulsion of the transfer fluid droplet 5-10 min after the transfer. This seemed to be due to contraction of the uterus in response to mechanical stimulation, although the patient rarely felt contractions. Delayed expulsion was observed after 7 transfers in 32 patients (22%). 5 of these patients became pregnant (16%). The mean number of embryos per transfer was 1 - 7. A subsequent series of 28 patients was pretreated with 550 mg naproxen given orally 2 h before transfer, and another 275-550 mg was given 30 min before transfer. Leakage was noted in 5 women (18%), but the volume expelled seemed smaller and the expulsion less forceful than it had been in the untreated series of patients. 8 women became pregnant (29%) after naproxen pretreatment. The mean number of embryos per transfer was 1-7, as before. The difference in pregnancy rates between the two series is not significant (p=0-2) and no firm conclusion about the possible efficacy of naproxen can be drawn. However, our results are consistent with other evidence, not supported by direct observation, that expulsion of embryos may contribute to IVF pregnancy failure. For example, Meldrum and associatesI have reported an improvement in pregnancy rates from 16% to 32% when the volume of fluid and air in which embryos were transferred was reduced. Our observation that delayed expulsion of transfer fluid after embryo replacement is common in human IVF cycles should provide a stimulus for careful analysis of methods for its reduction or elimination. of Obstetrics &
Department Gynecology, Fairfax Hospital, Fairfax, Virginia 22031, USA; and Medical College of Virginia 1 Meldrum on in
JOSEPH D. SCHULMAN
D, Steingold KA, de Ziegler D, et al. Presented at Fourth World Conference
Vitro Fertilization
(Melbourne, November 1985), abstr
Wernicke’s encephalopathy, his neurological condition deteriorated and he was referred to our hospital. On admission he was sleepy, displayed moderate hypoventilation, and could not raise his legs. Arterial blood gas measurements were: pH 7-41, pCO2 47-6 mm Hg, p02 45 mm Hg, and actual bicarbonate 29 - 6 mmol/1. Continuation of the supplements did not prove helpful. 2 days later further blood tests revealed severe hypophosphataemia (0-21 mmol/l; normal 0-85-1-40). He was given oral potassium phosphate and the sleepiness and weakness disappeared in a few hours, making a causal relation between the hypophosphataemia and the neurological disorders highly probable. 2 days later electromyography disclosed only moderate
polyneuropathy. This patient’s neurological signs and symptoms were logically interpreted as consistent with Wernicke’s encephalopathy. However, alcoholism, alcohol withdrawal, and respiratory insufficiency also known to contribute to acute severe hypophosphataemia 1-5 and the symptoms related to hypophosphataemia closely resemble the signs of Wernicke’s encephalopathy, including somnolence, confusion, gaze paresis, limb ataxia, muscular weakness, and areflexia. 1-3 Thus the diagnosis of acute severe hypophosphataemia may easily be missed, accounts of it being so sparse in neurological texts. Although acute severe hypophosphataemia is commonly seen as a complication of hyper alimentation, 6 NewmanS found that even oral alimentation may precipitate hypophosphataemia-related acute paralysis in malnourished phosphorus-depleted alcoholics. This was confirmed in our patient, whose severe weakness was probably due to decreased concentration of adenosine triphosphate in skeletal muscles;’his normal serum creatine kinase activity (46 IU/1) excluded rhabdomyolysis.7 Serum phosphorus should be measured in all alcoholics who present with symptoms suggesting Wernicke’s encephalopathy, especially when thiamine supplementation does not result in clinical improvement. Neurological textbooks should mention this condition in lists of electrolyte disturbances associated with neurological disorders. are
Department of Neurology, St Lucas Ziekenhuis, 1061 AE Amsterdam, Netherlands
J. VANNESTE
J. HAGE
1 Layzer RB Disorders of phosphorus metabolism. In: Neuromuscular manifestations of systemic disease. Philadelphia: FA Davis, 1985: 67-77. 2. Lotz M, Zisman E, Bartter FC. Evidence for a phosphorus-depletion syndrome in man N Eng J Med 1968; 278: 409-15. 3. Knochel JP The pathophysiology and clinical characteristics of severe hypophosphatemia Arch Intern Med 1977; 137: 203-20. 4. Territo MC, Tanaka KR Hypophosphatemia in chronic alcoholism. Arch Intern Med
82.
1973; 5 Newman
134: 445-47.
JH, Neff TA, Ziporin
P. Acute respiratory failure associated with 1101-03. 6. Silvis SE, Paragas PD. Paresthesias, weakness, seizures and hypophosphatemia in patients receiving hyperalimentation. Gastroenterology 1972; 62: 513-20 7. Knochel JP, Bilbrey GL, Fuller TJ, et al. The muscle cell in chronic alcoholism: the possible role of phosphate depletion in alcoholic myopathy Ann NY Accad Sci 1975; 252: 274-86.
hypophosphatemia N Engl J Med 1977; 296:
ACUTE SEVERE HYPOPHOSPHATAEMIA MIMICKING WERNICKE’S ENCEPHALOPATHY
SIR,-Neurological textbooks, with one exception,’ do not mention acute severe hypophosphataemia as a potential cause of neurological disorders. This blind spot may lead to a diagnostic delay, especially when the clinical features suggest a much more familiar neurological syndrome such as Wernicke’s encephalopathy. A 56-year-old alcoholic was admitted to another hospital because of increasing apathy, generalised muscular weakness, and fever. He malnourished man with a temperature of 39-8°C, a blood pressure of 90/60 mm Hg, and signs of lobar pneumonia. Abnormal neurological findings consisted of disorientation, hallucinations, tremor, gaze paresis, respiratory weakness, severe paresis of the legs, paraesthesiae, and areflexia. The erythrocyte sedimentation rate was 110 mm/h, liver enzymes were moderately increased, and there was hypokalaemia (2 - 5 mmol/1). Serum thiamine concentration and transketolase activity were not measured. He was treated with amoxycillin, haloperidol, supplementation with potassium, magnesium, and vitamins, and oxygen. Normal food intake was still possible. Despite this treatment for a presumptive diagnosis of early delirium tremens and
was a
AMOUNTS OF FEVERFEW IN COMMERCIAL PREPARATIONS OF THE HERB
SIR,-Extracts of feverfew (Tanacetum parthenium) inhibit secretory
activity
in blood
platelets
and
polymorphonuclear
leucocytes,and these effects in vitro may be relevant to any clinical effects of the herb. In the double-blind trial in migrainefeverfew supplied in specially prepared capsules. In view of the possible benefits of feverfew we need to know the activity of commercial preparations. Using an assay based on inhibition of secretory activity in platelets we have analysed some commercial preparations and compared the results with those obtained using air-dried leaves taken from feverfew plants grown in the Department of Botany, University of Nottingham. Chloroform extracts of leaves, tablets, and drops were filtered and dried under nitrogen. The residues were dissolved in phosphate buffered saline, pH 7 - 4, and then tested for their capacity to inhibit release of 14 C-serotonin from pre-labelled platelets in platelet-rich was