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Endometriosis-infertility link explained?
SCIENCE AND MEDICINE
Endometriosis-infertility link explained? nfertility in women with mild endometriosis may be explained, at least in part, by a lack of certain proteins in the peritoneal fluid, says Robert Lessey (University of North Carolina, Chapel Hill, NC, USA). “Doctors like to lump everyone together, but not everyone with endometriosis is the same. Now we have a marker which may help identify those women who really need therapy.” Lessey and co-workers injected peritoneal fluid from women with and without mild endometriosis into recently mated mice around the time of embryo implantation. Mice given fluid from infertile women with endometriosis had fewer implantations than did mice receiving fluid from fertile women or from women with recently treated endometriosis; they also had reduced uterine concentrations of leukaemia inhibitory factor and did not express alphavbeta3 integrin. Embryo implantations may have been adversely affected by the infertile women’s peritoneal fluid, suggest the authors (Fertil Steril 2000; 74: 41–48).
I
missing alphavbeta3, its use is “preBecause about half of women with mature”, he says, since some women mild endometriosis have no problem without alphavbeta3 are fertile. getting pregnant, a link with infertil“Combinations of ity is controversial, markers might be explains Lessey. Rights were not granted more specific.” “Those who don’t “There are lots of get pregnant are to include this image in factors out there”, given the diagnosis electronic media. Please affirms Bryan of ‘unexplained refer to the printed Cowan, spokesperinfertility’. Yet they journal. son for the seem to have bioAmerican Society chemical evidence of Reproductive that something is Medicine. “They different, and these proteins are part of Does endometriosis cause infertility? affect sperm function, macrophage that difference.” activation, peritoneal and tubal Thus, he insists, the absence of responses. So much is going on, and alphavbeta3 and reduced leukaemia just about everything that’s been inhibitory factor “could discriminate tested shows differences, so this is those women with serious defects” unlikely to be the final link.” In addiwhich really do interfere with implantion, “the peritoneal fluid is outside tation. Such women could be treated of the uterus, and the endometrium with surgical (lasers) or medical being tested is on the inside. We (gonadotrophin-releasing hormone) have a big leap to demonstrate that techniques to improve their chances the stuff on the outside of the uterus of conceiving, he says. can actually influence the A US company has started marketendometrium”, he concludes. ing a test of uterine receptivity based on these markers, notes Lessey. But although the test detects women Marilynn Larkin
News in brief
Dopamine hypothesis gains more support
Mutation linked to hypertension Hypertension threatens some 8 million pregnant women and their fetuses each year. Now, researchers report a link with a mutation in the mineralocorticoid receptor. In the presence of the high concentrations of progesterone in the bloodstream of pregnant women, the mutated receptor—that functions to trigger the kidney to reabsorb more salt—is overstimulated, causing dangerously high blood pressure. The investigators, however, remain cautious about changing treatment guidelines (Science 2000; 289: 119-23).
T
Awake during bypass A 51-yearold patient at the Pittsburgh Medical Centre recently underwent beating-heart bypass surgery while awake. Instead of an endotracheal anaesthesia, the patient was given an epidural anaesthetic which numbed his entire chest whilst allowing him to talk to operating staff throughout the proceedings. Being awake, say the investigators, makes the procedure more tolerable, and would perhaps mean only an overnight stay in hospital.
140
he dopamine hypothesis of schizophrenia gained further credibility this week with the publication of a paper showing that people with schizophrenia have increased synaptic dopamine concentrations, as well as increased numbers of dopamine type-2 (D2) receptors, compared with controls. “Because all antipsychotic drugs are antagonists at the D2 receptor, an alteration of dopamine transmission at this receptor has long been suspected to play a role in the pathophysiology of schizophrenia”, explains Anissa Abi-Dargham (Columbia University College of Physicians and Surgeons, New York, NY, USA), the lead investigator. However, since there is no direct way of measuring dopamine concentrations in the human brain, previous brain imaging studies have not been able to identify definitively the underlying pathophysiology of schizophrenia. The researchers of the current study circumvented this problem by using single-photon computerised emission tomography (SPECT) to measure the amount of the radiobenzamide [123I]IBZM that
binds to D2 receptors. This gave an indication of the number of “spare” D2 receptors that did not have dopamine molecules bound to them. Oral administration of alphamethylparatyrosine (a-MPT) over 2 days, to deplete endogenous dopamine, resulted in an increase in [123I]IBZM binding by 19% in people with schizophrenia, but only 9% in controls. According to the authors, these results indicate that schizophrenia patients have higher dopamine concentrations and more D2 receptors than controls (Proc Natl Acad Sci USA 2000; 97: 8104–09). “This will be seen as a very important study in the history of schizophrenia research”, says Shitij Kapur (University of Toronto, ON, Canada). “Of particular interest is that when the schizophrenia patients were subsequently treated with antipsychotics, the ones that responded best to treatment were those with the highest endogenous dopamine concentrations at baseline.” James Butcher
THE LANCET • Vol 356 • July 8, 2000
For personal use only. Not to be reproduced without permission of The Lancet.
Endometriosis-infertility link explained? nfertility in women with mild endometriosis may be explained, at least in part, by a lack of certain proteins in the peritoneal fluid, says Robert Lessey (University of North Carolina, Chapel Hill, NC, USA). “Doctors like to lump everyone together, but not everyone with endometriosis is the same. Now we have a marker which may help identify those women who really need therapy.” Lessey and co-workers injected peritoneal fluid from women with and without mild endometriosis into recently mated mice around the time of embryo implantation. Mice given fluid from infertile women with endometriosis had fewer implantations than did mice receiving fluid from fertile women or from women with recently treated endometriosis; they also had reduced uterine concentrations of leukaemia inhibitory factor and did not express alphavbeta3 integrin. Embryo implantations may have been adversely affected by the infertile women’s peritoneal fluid, suggest the authors (Fertil Steril 2000; 74: 41–48).
I
missing alphavbeta3, its use is “preBecause about half of women with mature”, he says, since some women mild endometriosis have no problem without alphavbeta3 are fertile. getting pregnant, a link with infertil“Combinations of ity is controversial, markers might be explains Lessey. Rights were not granted more specific.” “Those who don’t “There are lots of get pregnant are to include this image in factors out there”, given the diagnosis electronic media. Please affirms Bryan of ‘unexplained refer to the printed Cowan, spokesperinfertility’. Yet they journal. son for the seem to have bioAmerican Society chemical evidence of Reproductive that something is Medicine. “They different, and these proteins are part of Does endometriosis cause infertility? affect sperm function, macrophage that difference.” activation, peritoneal and tubal Thus, he insists, the absence of responses. So much is going on, and alphavbeta3 and reduced leukaemia just about everything that’s been inhibitory factor “could discriminate tested shows differences, so this is those women with serious defects” unlikely to be the final link.” In addiwhich really do interfere with implantion, “the peritoneal fluid is outside tation. Such women could be treated of the uterus, and the endometrium with surgical (lasers) or medical being tested is on the inside. We (gonadotrophin-releasing hormone) have a big leap to demonstrate that techniques to improve their chances the stuff on the outside of the uterus of conceiving, he says. can actually influence the A US company has started marketendometrium”, he concludes. ing a test of uterine receptivity based on these markers, notes Lessey. But although the test detects women Marilynn Larkin
News in brief
Dopamine hypothesis gains more support
Mutation linked to hypertension Hypertension threatens some 8 million pregnant women and their fetuses each year. Now, researchers report a link with a mutation in the mineralocorticoid receptor. In the presence of the high concentrations of progesterone in the bloodstream of pregnant women, the mutated receptor—that functions to trigger the kidney to reabsorb more salt—is overstimulated, causing dangerously high blood pressure. The investigators, however, remain cautious about changing treatment guidelines (Science 2000; 289: 119-23).
T
Awake during bypass A 51-yearold patient at the Pittsburgh Medical Centre recently underwent beating-heart bypass surgery while awake. Instead of an endotracheal anaesthesia, the patient was given an epidural anaesthetic which numbed his entire chest whilst allowing him to talk to operating staff throughout the proceedings. Being awake, say the investigators, makes the procedure more tolerable, and would perhaps mean only an overnight stay in hospital.
140
he dopamine hypothesis of schizophrenia gained further credibility this week with the publication of a paper showing that people with schizophrenia have increased synaptic dopamine concentrations, as well as increased numbers of dopamine type-2 (D2) receptors, compared with controls. “Because all antipsychotic drugs are antagonists at the D2 receptor, an alteration of dopamine transmission at this receptor has long been suspected to play a role in the pathophysiology of schizophrenia”, explains Anissa Abi-Dargham (Columbia University College of Physicians and Surgeons, New York, NY, USA), the lead investigator. However, since there is no direct way of measuring dopamine concentrations in the human brain, previous brain imaging studies have not been able to identify definitively the underlying pathophysiology of schizophrenia. The researchers of the current study circumvented this problem by using single-photon computerised emission tomography (SPECT) to measure the amount of the radiobenzamide [123I]IBZM that
binds to D2 receptors. This gave an indication of the number of “spare” D2 receptors that did not have dopamine molecules bound to them. Oral administration of alphamethylparatyrosine (a-MPT) over 2 days, to deplete endogenous dopamine, resulted in an increase in [123I]IBZM binding by 19% in people with schizophrenia, but only 9% in controls. According to the authors, these results indicate that schizophrenia patients have higher dopamine concentrations and more D2 receptors than controls (Proc Natl Acad Sci USA 2000; 97: 8104–09). “This will be seen as a very important study in the history of schizophrenia research”, says Shitij Kapur (University of Toronto, ON, Canada). “Of particular interest is that when the schizophrenia patients were subsequently treated with antipsychotics, the ones that responded best to treatment were those with the highest endogenous dopamine concentrations at baseline.” James Butcher
THE LANCET • Vol 356 • July 8, 2000
For personal use only. Not to be reproduced without permission of The Lancet.