Kate Johnson

BOSTON — Statin therapy significantly reduces the risk of sudden cardiac death independent of its effect on cholesterol, according to a metaanalysis of 12 studies.

“This is not a surprise because statins have a variety of effects, and it is these effects both within the heart and outside the heart that we think explain this finding,” said Dr. Derek Exner of the University of Calgary (Alta).

Multiple randomized trials have shown that statin therapy significantly reduces mortality in patients with ischemic heart disease, he said in an interview. However, their impact specifically on sudden cardiac death (SCD) has been unclear, although there is growing evidence that they have antiarrhythmic effects in addition to possible effects on platelet function and vascular tone.

His study, presented as a poster at the annual meeting of the Heart Rhythm Society, included 41,167 patients in 12 long-term, randomized, placebo-controlled trials of statin therapy for either primary or secondary prevention of coronary artery disease. During the mean follow-up of 3 years, 20% of the deaths (912) were categorized as SCDs—425 in the statin groups and 487 in the placebo groups. Deaths by all causes were observed in 2,243 and 2,708 of the statin and placebo groups, respectively.

By using a random effects model, Dr. Exner calculated that statin therapy reduced the odds of death by 22% and the odds of SCD by 14%, independent of changes in LDL and HDL cholesterol levels. The reduction in the odds of SCD did not differ by sex or by diabetes status. However, the magnitude of benefit was greater in secondary prevention, with an odds reduction of 18%, compared with 5% in primary prevention.

“This is a fairly large sample size of over 40,000 patients,” Dr. Exner said. “It's the best we can do with the data, and we can feel pretty confident in the results. It suggests that the SCD protection is not explained, at least in a large part, by the change in cholesterol. Could it be partly related? It could be, but not statistically.”

BOSTON — Statin therapy significantly reduces the risk of sudden cardiac death independent of its effect on cholesterol, according to a metaanalysis of 12 studies.

“This is not a surprise because statins have a variety of effects, and it is these effects both within the heart and outside the heart that we think explain this finding,” said Dr. Derek Exner of the University of Calgary (Alta).

Multiple randomized trials have shown that statin therapy significantly reduces mortality in patients with ischemic heart disease, he said in an interview. However, their impact specifically on sudden cardiac death (SCD) has been unclear, although there is growing evidence that they have antiarrhythmic effects in addition to possible effects on platelet function and vascular tone.

His study, presented as a poster at the annual meeting of the Heart Rhythm Society, included 41,167 patients in 12 long-term, randomized, placebo-controlled trials of statin therapy for either primary or secondary prevention of coronary artery disease. During the mean follow-up of 3 years, 20% of the deaths (912) were categorized as SCDs—425 in the statin groups and 487 in the placebo groups. Deaths by all causes were observed in 2,243 and 2,708 of the statin and placebo groups, respectively.

By using a random effects model, Dr. Exner calculated that statin therapy reduced the odds of death by 22% and the odds of SCD by 14%, independent of changes in LDL and HDL cholesterol levels. The reduction in the odds of SCD did not differ by sex or by diabetes status. However, the magnitude of benefit was greater in secondary prevention, with an odds reduction of 18%, compared with 5% in primary prevention.

“This is a fairly large sample size of over 40,000 patients,” Dr. Exner said. “It's the best we can do with the data, and we can feel pretty confident in the results. It suggests that the SCD protection is not explained, at least in a large part, by the change in cholesterol. Could it be partly related? It could be, but not statistically.”

BOSTON — Statin therapy significantly reduces the risk of sudden cardiac death independent of its effect on cholesterol, according to a metaanalysis of 12 studies.

“This is not a surprise because statins have a variety of effects, and it is these effects both within the heart and outside the heart that we think explain this finding,” said Dr. Derek Exner of the University of Calgary (Alta).

Multiple randomized trials have shown that statin therapy significantly reduces mortality in patients with ischemic heart disease, he said in an interview. However, their impact specifically on sudden cardiac death (SCD) has been unclear, although there is growing evidence that they have antiarrhythmic effects in addition to possible effects on platelet function and vascular tone.

His study, presented as a poster at the annual meeting of the Heart Rhythm Society, included 41,167 patients in 12 long-term, randomized, placebo-controlled trials of statin therapy for either primary or secondary prevention of coronary artery disease. During the mean follow-up of 3 years, 20% of the deaths (912) were categorized as SCDs—425 in the statin groups and 487 in the placebo groups. Deaths by all causes were observed in 2,243 and 2,708 of the statin and placebo groups, respectively.

By using a random effects model, Dr. Exner calculated that statin therapy reduced the odds of death by 22% and the odds of SCD by 14%, independent of changes in LDL and HDL cholesterol levels. The reduction in the odds of SCD did not differ by sex or by diabetes status. However, the magnitude of benefit was greater in secondary prevention, with an odds reduction of 18%, compared with 5% in primary prevention.

“This is a fairly large sample size of over 40,000 patients,” Dr. Exner said. “It's the best we can do with the data, and we can feel pretty confident in the results. It suggests that the SCD protection is not explained, at least in a large part, by the change in cholesterol. Could it be partly related? It could be, but not statistically.”

PRAGUE — Single embryo transfer does not lower success rates compared to double embryo transfer in most patients who need preimplantation genetic diagnosis, according to a study presented at the annual meeting of the European Society of Human Reproduction and Embryology.

However, one subset of patients needing preimplantation genetic diagnosis (PGD)—those with translocations—may need more than one embryo transferred to achieve adequate pregnancy and delivery rates, reported Dr. Patricio Donoso of University Hospital, Dutch-speaking Free University Brussels, Belgium.

It has been suggested that patients undergoing PGD may have a smaller chance of getting pregnant after in vitro fertilization (IVF) than do patients who do not undergo PGD, Dr. Donoso said in an interview. Although there is still some debate about whether the PGD biopsy is slightly harmful to the embryo, the main reason for concern is that PGD often identifies many embryos as unsuitable for transfer. “In regular IVF, we usually select the most morphologically normal-looking embryo for transfer. In PGD patients, the healthy embryo is not necessarily the one with the best morphology, so that makes embryo selection more difficult,” he said.

His retrospective study of PGD patients was performed both before and after a Belgian law mandated single embryo transfer (SET) in all women under 36 years of age undergoing their first trial of IVF. The study included 50 PGD patients who received double embryo transfer (DET) between 2002 and 2003 (before the law was implemented) and 55 PGD patients who received SET after implementation of the law in July 2004.

Most patients had experienced recurrent miscarriage, and indications for PGD included monogenic disorders, such as myotonic dystrophy and cystic fibrosis, and translocations.

The study found no statistical difference in delivery rates between the DET and SET groups overall (32% vs. 25.5%); the rate of multiple pregnancies was significantly different—31% in the DET group and none in the SET group.

However, in the subgroup of patients with translocations, among those who received only one embryo there was a reduced delivery rate compared to those who received DET (18% vs. 40%). Although this trend did not reach statistical significance, Dr. Donoso said he expects it will with the addition of more patients. “If this trend continues, maybe we will have to discuss transferring more than one embryo in these patients, which would mean changing the law in Belgium,” said Dr. Donoso.

However, he said collecting a big enough series to explore this trend will be very difficult, because it is not a frequently occurring pathology.

PRAGUE — Single embryo transfer does not lower success rates compared to double embryo transfer in most patients who need preimplantation genetic diagnosis, according to a study presented at the annual meeting of the European Society of Human Reproduction and Embryology.

However, one subset of patients needing preimplantation genetic diagnosis (PGD)—those with translocations—may need more than one embryo transferred to achieve adequate pregnancy and delivery rates, reported Dr. Patricio Donoso of University Hospital, Dutch-speaking Free University Brussels, Belgium.

It has been suggested that patients undergoing PGD may have a smaller chance of getting pregnant after in vitro fertilization (IVF) than do patients who do not undergo PGD, Dr. Donoso said in an interview. Although there is still some debate about whether the PGD biopsy is slightly harmful to the embryo, the main reason for concern is that PGD often identifies many embryos as unsuitable for transfer. “In regular IVF, we usually select the most morphologically normal-looking embryo for transfer. In PGD patients, the healthy embryo is not necessarily the one with the best morphology, so that makes embryo selection more difficult,” he said.

His retrospective study of PGD patients was performed both before and after a Belgian law mandated single embryo transfer (SET) in all women under 36 years of age undergoing their first trial of IVF. The study included 50 PGD patients who received double embryo transfer (DET) between 2002 and 2003 (before the law was implemented) and 55 PGD patients who received SET after implementation of the law in July 2004.

Most patients had experienced recurrent miscarriage, and indications for PGD included monogenic disorders, such as myotonic dystrophy and cystic fibrosis, and translocations.

The study found no statistical difference in delivery rates between the DET and SET groups overall (32% vs. 25.5%); the rate of multiple pregnancies was significantly different—31% in the DET group and none in the SET group.

However, in the subgroup of patients with translocations, among those who received only one embryo there was a reduced delivery rate compared to those who received DET (18% vs. 40%). Although this trend did not reach statistical significance, Dr. Donoso said he expects it will with the addition of more patients. “If this trend continues, maybe we will have to discuss transferring more than one embryo in these patients, which would mean changing the law in Belgium,” said Dr. Donoso.

However, he said collecting a big enough series to explore this trend will be very difficult, because it is not a frequently occurring pathology.

PRAGUE — Single embryo transfer does not lower success rates compared to double embryo transfer in most patients who need preimplantation genetic diagnosis, according to a study presented at the annual meeting of the European Society of Human Reproduction and Embryology.

However, one subset of patients needing preimplantation genetic diagnosis (PGD)—those with translocations—may need more than one embryo transferred to achieve adequate pregnancy and delivery rates, reported Dr. Patricio Donoso of University Hospital, Dutch-speaking Free University Brussels, Belgium.

It has been suggested that patients undergoing PGD may have a smaller chance of getting pregnant after in vitro fertilization (IVF) than do patients who do not undergo PGD, Dr. Donoso said in an interview. Although there is still some debate about whether the PGD biopsy is slightly harmful to the embryo, the main reason for concern is that PGD often identifies many embryos as unsuitable for transfer. “In regular IVF, we usually select the most morphologically normal-looking embryo for transfer. In PGD patients, the healthy embryo is not necessarily the one with the best morphology, so that makes embryo selection more difficult,” he said.

His retrospective study of PGD patients was performed both before and after a Belgian law mandated single embryo transfer (SET) in all women under 36 years of age undergoing their first trial of IVF. The study included 50 PGD patients who received double embryo transfer (DET) between 2002 and 2003 (before the law was implemented) and 55 PGD patients who received SET after implementation of the law in July 2004.

Most patients had experienced recurrent miscarriage, and indications for PGD included monogenic disorders, such as myotonic dystrophy and cystic fibrosis, and translocations.

The study found no statistical difference in delivery rates between the DET and SET groups overall (32% vs. 25.5%); the rate of multiple pregnancies was significantly different—31% in the DET group and none in the SET group.

However, in the subgroup of patients with translocations, among those who received only one embryo there was a reduced delivery rate compared to those who received DET (18% vs. 40%). Although this trend did not reach statistical significance, Dr. Donoso said he expects it will with the addition of more patients. “If this trend continues, maybe we will have to discuss transferring more than one embryo in these patients, which would mean changing the law in Belgium,” said Dr. Donoso.

However, he said collecting a big enough series to explore this trend will be very difficult, because it is not a frequently occurring pathology.

PRAGUE — Europe maintained its in vitro fertilization success rates in 2003 compared with the previous year despite a reduction in multiple pregnancies, according to data presented at the annual meeting of the European Society of Human Reproduction and Embryology.

The European in vitro fertilization (IVF) clinical pregnancy rate was 29.5% per embryo transfer, reported Dr. Anders Nyboe Andersen, coordinator of the European IVF Monitoring (EIM) Consortium.

In comparison, the latest figures (2004) from the United States' Society for Assisted Reproductive Technology (SART) show a 40.6% pregnancy rate per embryo transfer, said California fertility expert Dr. David Adamson in an interview.

In the United States, that figure translates to a live birth rate of roughly 33% per embryo transfer across all age groups (42.5% in women under age 35 years), said Dr. Adamson. The European live birth rate per embryo transfer is not known because the EIM Consortium includes 28 European countries and does not routinely follow IVF patients beyond the ultrasound confirmation of a gestational sac, said Dr. Andersen, also of the University of Copenhagen. However, assuming similar rates of miscarriage in Europe and the United States, the European live birth rate per embryo transfer would be roughly 24%. (In its 2002 World Report on IVF, the International Committee for Monitoring Assisted Reproduction reports an IVF delivery rate of 17% for Europe and 25% for the United States.)

Although this calculation suggests Europe has lower IVF success rates compared with the United States, Europe also reports lower multiple pregnancy rates—but an exact comparison is difficult to make. The latest figures from the EIM Consortium show that 22% of all IVF deliveries in Europe were twins and 1.1% were triplets (down from a twin rate of 23% and a triplet rate of 1.3% the previous year). However, given the fact that the consortium does not keep a final tally of all IVF deliveries, its figure on multiple birth rates can only be an estimate. In comparison, the United States records multiple pregnancies, not multiple births (which tend to be lower because of the high rate of miscarriage) and last year reported a twin pregnancy rate of 27% and a 4.5% rate of triplet and higher-order pregnancies, according to Dr. William Gibbons, president of SART.

Europe's reportedly lower multiple pregnancy rates are attributed to its transition toward single embryo transfer (SET), and a continuing trend toward the transfer of fewer embryos. Overall, the 28 European countries in the EIM Consortium reported a 16% rate of SET in their IVF cycles, said Dr. Nyboe Andersen. This is in contrast to an elective SET rate of 1.2% in the United States, according to SART—although the overall SET rate is presumed to be higher, since other U.S. patients receive SET nonelectively because they have only one good embryo to transfer. According to the 2002 World Report on IVF, the average number of embryos transferred in European patients was 2.2. vs. 2.9 in the United States.

Guidelines released at the end of 2004 from the American Society for Reproductive Medicine and SART recommended for the first time that SET should be considered “in patients with the most favorable prognosis” (Fertil. Steril. 2004;82:773–4), and consequences of those guidelines may be reflected in the 2005 data. However, SET is a hard sell in the United States compared with Europe, because while many European countries provide some coverage for IVF treatment, most U.S. patients pay for it themselves.

“There is a certain amount of fear among [U.S.] centers that if they do SET, they may see a dramatic fall in pregnancy rates, which in turn may cause patients to go elsewhere for treatment,” said Dr. Bradley Van Voorhis, of the University of Iowa Hospitals and Clinics in Iowa City.

Indeed, the world's first randomized trial comparing SET with double embryo transfer (DET) in an unselected group of women did much to fuel such fears (Hum. Reprod. 2006;21:338–43). Investigators in the Netherlands found that although SET reduced multiple pregnancies in unselected patients, it also significantly reduced the overall pregnancy rate compared with DET (21.4% vs. 40.3%), while in a more select group of patients (younger and with at least one good-quality embryo), the pregnancy rates in the two groups did not differ significantly (33% for SET vs. 30% for DET).

Building on this experience, Dr. Van Voorhis' clinic implemented a mandatory SET policy 2 years ago for select women with a good prognosis and high risk for multiple pregnancy, and noted no decline in success rates.

But achieving this kind of success for SET—maintaining pregnancy rates while reducing the number of embryos transferred—involves a complex art of balancing safety and success, choosing which patients can receive fewer embryos, and choosing which embryos are most likely to result in a pregnancy, said Dr. Adamson.

“SET is a very good and important strategy, and I think that we need to do more of it in the United States in order to reduce the rate of multiple pregnancies,” he said. “But this is not something that works for all patients, and that really needs to be strongly emphasized. It's not possible to make a single rule that applies to all patients; we certainly do not believe that in the United States. … We don't believe that regulation by the government which tells patients how they should make reproductive choices is the appropriate thing to do.”

That type of government regulation is largely responsible for Europe's high SET rate. The free IVF treatment provided by many European countries comes with legislative strings attached that mandate SET or severely restrict the number of embryos placed in certain women. European physicians have feared that this approach could limit pregnancy, and this is generally assumed to be one of the reasons for Europe's lower overall IVF pregnancy rate.

But certain European countries such as Sweden appear to have mastered the art of using SET effectively. “In Sweden we have shown no overall decline in pregnancy rates,” said Dr. Karl Nygren, chair of the EIM Consortium. “It has been possible to maintain the pregnancy rate even with a dramatic shift to 70% SET in Sweden, and we have reduced our twin pregnancy rate to 5%,” Dr. Nygren said. The consortium reported a Swedish pregnancy rate of roughly 34% per embryo transfer, which is significantly lower than the U.S. rate of 40.6%.

PRAGUE — Europe maintained its in vitro fertilization success rates in 2003 compared with the previous year despite a reduction in multiple pregnancies, according to data presented at the annual meeting of the European Society of Human Reproduction and Embryology.

The European in vitro fertilization (IVF) clinical pregnancy rate was 29.5% per embryo transfer, reported Dr. Anders Nyboe Andersen, coordinator of the European IVF Monitoring (EIM) Consortium.

In comparison, the latest figures (2004) from the United States' Society for Assisted Reproductive Technology (SART) show a 40.6% pregnancy rate per embryo transfer, said California fertility expert Dr. David Adamson in an interview.

In the United States, that figure translates to a live birth rate of roughly 33% per embryo transfer across all age groups (42.5% in women under age 35 years), said Dr. Adamson. The European live birth rate per embryo transfer is not known because the EIM Consortium includes 28 European countries and does not routinely follow IVF patients beyond the ultrasound confirmation of a gestational sac, said Dr. Andersen, also of the University of Copenhagen. However, assuming similar rates of miscarriage in Europe and the United States, the European live birth rate per embryo transfer would be roughly 24%. (In its 2002 World Report on IVF, the International Committee for Monitoring Assisted Reproduction reports an IVF delivery rate of 17% for Europe and 25% for the United States.)

Although this calculation suggests Europe has lower IVF success rates compared with the United States, Europe also reports lower multiple pregnancy rates—but an exact comparison is difficult to make. The latest figures from the EIM Consortium show that 22% of all IVF deliveries in Europe were twins and 1.1% were triplets (down from a twin rate of 23% and a triplet rate of 1.3% the previous year). However, given the fact that the consortium does not keep a final tally of all IVF deliveries, its figure on multiple birth rates can only be an estimate. In comparison, the United States records multiple pregnancies, not multiple births (which tend to be lower because of the high rate of miscarriage) and last year reported a twin pregnancy rate of 27% and a 4.5% rate of triplet and higher-order pregnancies, according to Dr. William Gibbons, president of SART.

Europe's reportedly lower multiple pregnancy rates are attributed to its transition toward single embryo transfer (SET), and a continuing trend toward the transfer of fewer embryos. Overall, the 28 European countries in the EIM Consortium reported a 16% rate of SET in their IVF cycles, said Dr. Nyboe Andersen. This is in contrast to an elective SET rate of 1.2% in the United States, according to SART—although the overall SET rate is presumed to be higher, since other U.S. patients receive SET nonelectively because they have only one good embryo to transfer. According to the 2002 World Report on IVF, the average number of embryos transferred in European patients was 2.2. vs. 2.9 in the United States.

Guidelines released at the end of 2004 from the American Society for Reproductive Medicine and SART recommended for the first time that SET should be considered “in patients with the most favorable prognosis” (Fertil. Steril. 2004;82:773–4), and consequences of those guidelines may be reflected in the 2005 data. However, SET is a hard sell in the United States compared with Europe, because while many European countries provide some coverage for IVF treatment, most U.S. patients pay for it themselves.

“There is a certain amount of fear among [U.S.] centers that if they do SET, they may see a dramatic fall in pregnancy rates, which in turn may cause patients to go elsewhere for treatment,” said Dr. Bradley Van Voorhis, of the University of Iowa Hospitals and Clinics in Iowa City.

Indeed, the world's first randomized trial comparing SET with double embryo transfer (DET) in an unselected group of women did much to fuel such fears (Hum. Reprod. 2006;21:338–43). Investigators in the Netherlands found that although SET reduced multiple pregnancies in unselected patients, it also significantly reduced the overall pregnancy rate compared with DET (21.4% vs. 40.3%), while in a more select group of patients (younger and with at least one good-quality embryo), the pregnancy rates in the two groups did not differ significantly (33% for SET vs. 30% for DET).

Building on this experience, Dr. Van Voorhis' clinic implemented a mandatory SET policy 2 years ago for select women with a good prognosis and high risk for multiple pregnancy, and noted no decline in success rates.

But achieving this kind of success for SET—maintaining pregnancy rates while reducing the number of embryos transferred—involves a complex art of balancing safety and success, choosing which patients can receive fewer embryos, and choosing which embryos are most likely to result in a pregnancy, said Dr. Adamson.

“SET is a very good and important strategy, and I think that we need to do more of it in the United States in order to reduce the rate of multiple pregnancies,” he said. “But this is not something that works for all patients, and that really needs to be strongly emphasized. It's not possible to make a single rule that applies to all patients; we certainly do not believe that in the United States. … We don't believe that regulation by the government which tells patients how they should make reproductive choices is the appropriate thing to do.”

That type of government regulation is largely responsible for Europe's high SET rate. The free IVF treatment provided by many European countries comes with legislative strings attached that mandate SET or severely restrict the number of embryos placed in certain women. European physicians have feared that this approach could limit pregnancy, and this is generally assumed to be one of the reasons for Europe's lower overall IVF pregnancy rate.

But certain European countries such as Sweden appear to have mastered the art of using SET effectively. “In Sweden we have shown no overall decline in pregnancy rates,” said Dr. Karl Nygren, chair of the EIM Consortium. “It has been possible to maintain the pregnancy rate even with a dramatic shift to 70% SET in Sweden, and we have reduced our twin pregnancy rate to 5%,” Dr. Nygren said. The consortium reported a Swedish pregnancy rate of roughly 34% per embryo transfer, which is significantly lower than the U.S. rate of 40.6%.

PRAGUE — Europe maintained its in vitro fertilization success rates in 2003 compared with the previous year despite a reduction in multiple pregnancies, according to data presented at the annual meeting of the European Society of Human Reproduction and Embryology.

The European in vitro fertilization (IVF) clinical pregnancy rate was 29.5% per embryo transfer, reported Dr. Anders Nyboe Andersen, coordinator of the European IVF Monitoring (EIM) Consortium.

In comparison, the latest figures (2004) from the United States' Society for Assisted Reproductive Technology (SART) show a 40.6% pregnancy rate per embryo transfer, said California fertility expert Dr. David Adamson in an interview.

In the United States, that figure translates to a live birth rate of roughly 33% per embryo transfer across all age groups (42.5% in women under age 35 years), said Dr. Adamson. The European live birth rate per embryo transfer is not known because the EIM Consortium includes 28 European countries and does not routinely follow IVF patients beyond the ultrasound confirmation of a gestational sac, said Dr. Andersen, also of the University of Copenhagen. However, assuming similar rates of miscarriage in Europe and the United States, the European live birth rate per embryo transfer would be roughly 24%. (In its 2002 World Report on IVF, the International Committee for Monitoring Assisted Reproduction reports an IVF delivery rate of 17% for Europe and 25% for the United States.)

Although this calculation suggests Europe has lower IVF success rates compared with the United States, Europe also reports lower multiple pregnancy rates—but an exact comparison is difficult to make. The latest figures from the EIM Consortium show that 22% of all IVF deliveries in Europe were twins and 1.1% were triplets (down from a twin rate of 23% and a triplet rate of 1.3% the previous year). However, given the fact that the consortium does not keep a final tally of all IVF deliveries, its figure on multiple birth rates can only be an estimate. In comparison, the United States records multiple pregnancies, not multiple births (which tend to be lower because of the high rate of miscarriage) and last year reported a twin pregnancy rate of 27% and a 4.5% rate of triplet and higher-order pregnancies, according to Dr. William Gibbons, president of SART.

Europe's reportedly lower multiple pregnancy rates are attributed to its transition toward single embryo transfer (SET), and a continuing trend toward the transfer of fewer embryos. Overall, the 28 European countries in the EIM Consortium reported a 16% rate of SET in their IVF cycles, said Dr. Nyboe Andersen. This is in contrast to an elective SET rate of 1.2% in the United States, according to SART—although the overall SET rate is presumed to be higher, since other U.S. patients receive SET nonelectively because they have only one good embryo to transfer. According to the 2002 World Report on IVF, the average number of embryos transferred in European patients was 2.2. vs. 2.9 in the United States.

Guidelines released at the end of 2004 from the American Society for Reproductive Medicine and SART recommended for the first time that SET should be considered “in patients with the most favorable prognosis” (Fertil. Steril. 2004;82:773–4), and consequences of those guidelines may be reflected in the 2005 data. However, SET is a hard sell in the United States compared with Europe, because while many European countries provide some coverage for IVF treatment, most U.S. patients pay for it themselves.

“There is a certain amount of fear among [U.S.] centers that if they do SET, they may see a dramatic fall in pregnancy rates, which in turn may cause patients to go elsewhere for treatment,” said Dr. Bradley Van Voorhis, of the University of Iowa Hospitals and Clinics in Iowa City.

Indeed, the world's first randomized trial comparing SET with double embryo transfer (DET) in an unselected group of women did much to fuel such fears (Hum. Reprod. 2006;21:338–43). Investigators in the Netherlands found that although SET reduced multiple pregnancies in unselected patients, it also significantly reduced the overall pregnancy rate compared with DET (21.4% vs. 40.3%), while in a more select group of patients (younger and with at least one good-quality embryo), the pregnancy rates in the two groups did not differ significantly (33% for SET vs. 30% for DET).

Building on this experience, Dr. Van Voorhis' clinic implemented a mandatory SET policy 2 years ago for select women with a good prognosis and high risk for multiple pregnancy, and noted no decline in success rates.

But achieving this kind of success for SET—maintaining pregnancy rates while reducing the number of embryos transferred—involves a complex art of balancing safety and success, choosing which patients can receive fewer embryos, and choosing which embryos are most likely to result in a pregnancy, said Dr. Adamson.

“SET is a very good and important strategy, and I think that we need to do more of it in the United States in order to reduce the rate of multiple pregnancies,” he said. “But this is not something that works for all patients, and that really needs to be strongly emphasized. It's not possible to make a single rule that applies to all patients; we certainly do not believe that in the United States. … We don't believe that regulation by the government which tells patients how they should make reproductive choices is the appropriate thing to do.”

That type of government regulation is largely responsible for Europe's high SET rate. The free IVF treatment provided by many European countries comes with legislative strings attached that mandate SET or severely restrict the number of embryos placed in certain women. European physicians have feared that this approach could limit pregnancy, and this is generally assumed to be one of the reasons for Europe's lower overall IVF pregnancy rate.

But certain European countries such as Sweden appear to have mastered the art of using SET effectively. “In Sweden we have shown no overall decline in pregnancy rates,” said Dr. Karl Nygren, chair of the EIM Consortium. “It has been possible to maintain the pregnancy rate even with a dramatic shift to 70% SET in Sweden, and we have reduced our twin pregnancy rate to 5%,” Dr. Nygren said. The consortium reported a Swedish pregnancy rate of roughly 34% per embryo transfer, which is significantly lower than the U.S. rate of 40.6%.

Influenza vaccination appears to be safe in patients with quiescent systemic lupus erythematosus, although the overall efficacy of the immunization is decreased in them compared to controls, according to a new study.

In addition, there is a trend toward a further decrease in the vaccine's efficacy among systemic lupus erythematosus (SLE) patients taking azathioprine as compared with several other immunosuppressive drugs, reported Dr. A. Holvast from the University of Groningen, the Netherlands, and colleagues.

The study included 56 SLE patients with quiescent disease, defined as an SLE disease activity index (SLEDAI) of £5. Patients were divided into groups based on their use of immunosuppressive drugs, with 12 using no drugs, 17 using hydroxychloroquine (

All patients, along with 18 healthy controls, were vaccinated in October and November 2003 with Influvac (Solvay Pharmaceuticals Inc.), a trivalent influenza vaccine.

SLEDAI scores measured a mean of 30 days after vaccination did not differ significantly from baseline SLEDAI scores in any of the patient groups, and there were also no significant changes in patient-recorded visual analogue scores—suggesting that vaccination did not induce disease activity. “The immune response to influenza is generated during the first weeks following vaccination,” wrote the authors. “If vaccination were to enhance established autoimmunity, this would be expected to occur particularly during this early period.”

They noted that compared with controls, SLE patients had more systemic side effects of vaccination—although these were all mild. With respect to vaccination efficacy, the authors concluded that “SLE patients appear to have a decreased immune response, compared to healthy controls.”

Using blood samples taken at baseline and at the follow-up visit, the subjects' influenza antibody responses to A/H1N1, A/H3N2, and B/Hong Kong were measured in 3 ways: by assessment of a

Although the GMT increased after vaccination in all subjects and did not differ significantly between patients and controls, the authors suggested this was because prevaccination GMTs were higher in patients than in controls because of the patients' higher rate of vaccination in the previous year (77% vs. 22%).

Compared with controls, SLE patients had significantly fewer seroconversions against A/H1N1 and A/H3N2 (43% vs. 94% and 39% vs. 88%, respectively). SLE patients also had fewer seroconversions to B/Hong Kong, compared with controls (41% vs. 71%), although this difference was marginally significant.

No significant differences could be found overall between patients and controls in terms of the percent of people achieving a postvaccination titer of

After excluding all subjects who had been vaccinated the previous year, they found that significantly fewer SLE patients achieved seroconversions and protective titers to A/H1N1 and A/H3N2. (See seroconversion graph.)

“It is conceivable that SLE patients have an intrinsic [immunologic] defect that results in decreased responsiveness to vaccination,” wrote the authors, adding that the use of immunosuppressive drugs may further decrease the vaccination response in these patients. “SLE patients receiving azathioprine showed a trend towards a decreased immune response against influenza A/H3N2, compared with the other patient groups,” they wrote. “For A/H3N2, SLE patients receiving azathioprine had fewer fourfold titre rises than [did] the other patient groups (P = .041). Furthermore, a smaller proportion of the azathioprine group achieved titres of 40 or greater against A/H3N2 (P = .030), compared with the other patient groups.”(See immune response graph.)

The authors suggested that virosomal vaccines, which generate better cellular immune responses and enhance humoral immune responses, might improve the efficacy of vaccination in SLE patients.

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

Influenza vaccination appears to be safe in patients with quiescent systemic lupus erythematosus, although the overall efficacy of the immunization is decreased in them compared to controls, according to a new study.

In addition, there is a trend toward a further decrease in the vaccine's efficacy among systemic lupus erythematosus (SLE) patients taking azathioprine as compared with several other immunosuppressive drugs, reported Dr. A. Holvast from the University of Groningen, the Netherlands, and colleagues.

The study included 56 SLE patients with quiescent disease, defined as an SLE disease activity index (SLEDAI) of £5. Patients were divided into groups based on their use of immunosuppressive drugs, with 12 using no drugs, 17 using hydroxychloroquine (

All patients, along with 18 healthy controls, were vaccinated in October and November 2003 with Influvac (Solvay Pharmaceuticals Inc.), a trivalent influenza vaccine.

SLEDAI scores measured a mean of 30 days after vaccination did not differ significantly from baseline SLEDAI scores in any of the patient groups, and there were also no significant changes in patient-recorded visual analogue scores—suggesting that vaccination did not induce disease activity. “The immune response to influenza is generated during the first weeks following vaccination,” wrote the authors. “If vaccination were to enhance established autoimmunity, this would be expected to occur particularly during this early period.”

They noted that compared with controls, SLE patients had more systemic side effects of vaccination—although these were all mild. With respect to vaccination efficacy, the authors concluded that “SLE patients appear to have a decreased immune response, compared to healthy controls.”

Using blood samples taken at baseline and at the follow-up visit, the subjects' influenza antibody responses to A/H1N1, A/H3N2, and B/Hong Kong were measured in 3 ways: by assessment of a

Although the GMT increased after vaccination in all subjects and did not differ significantly between patients and controls, the authors suggested this was because prevaccination GMTs were higher in patients than in controls because of the patients' higher rate of vaccination in the previous year (77% vs. 22%).

Compared with controls, SLE patients had significantly fewer seroconversions against A/H1N1 and A/H3N2 (43% vs. 94% and 39% vs. 88%, respectively). SLE patients also had fewer seroconversions to B/Hong Kong, compared with controls (41% vs. 71%), although this difference was marginally significant.

No significant differences could be found overall between patients and controls in terms of the percent of people achieving a postvaccination titer of

After excluding all subjects who had been vaccinated the previous year, they found that significantly fewer SLE patients achieved seroconversions and protective titers to A/H1N1 and A/H3N2. (See seroconversion graph.)

“It is conceivable that SLE patients have an intrinsic [immunologic] defect that results in decreased responsiveness to vaccination,” wrote the authors, adding that the use of immunosuppressive drugs may further decrease the vaccination response in these patients. “SLE patients receiving azathioprine showed a trend towards a decreased immune response against influenza A/H3N2, compared with the other patient groups,” they wrote. “For A/H3N2, SLE patients receiving azathioprine had fewer fourfold titre rises than [did] the other patient groups (P = .041). Furthermore, a smaller proportion of the azathioprine group achieved titres of 40 or greater against A/H3N2 (P = .030), compared with the other patient groups.”(See immune response graph.)

The authors suggested that virosomal vaccines, which generate better cellular immune responses and enhance humoral immune responses, might improve the efficacy of vaccination in SLE patients.

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

Influenza vaccination appears to be safe in patients with quiescent systemic lupus erythematosus, although the overall efficacy of the immunization is decreased in them compared to controls, according to a new study.

In addition, there is a trend toward a further decrease in the vaccine's efficacy among systemic lupus erythematosus (SLE) patients taking azathioprine as compared with several other immunosuppressive drugs, reported Dr. A. Holvast from the University of Groningen, the Netherlands, and colleagues.

The study included 56 SLE patients with quiescent disease, defined as an SLE disease activity index (SLEDAI) of £5. Patients were divided into groups based on their use of immunosuppressive drugs, with 12 using no drugs, 17 using hydroxychloroquine (

All patients, along with 18 healthy controls, were vaccinated in October and November 2003 with Influvac (Solvay Pharmaceuticals Inc.), a trivalent influenza vaccine.

SLEDAI scores measured a mean of 30 days after vaccination did not differ significantly from baseline SLEDAI scores in any of the patient groups, and there were also no significant changes in patient-recorded visual analogue scores—suggesting that vaccination did not induce disease activity. “The immune response to influenza is generated during the first weeks following vaccination,” wrote the authors. “If vaccination were to enhance established autoimmunity, this would be expected to occur particularly during this early period.”

They noted that compared with controls, SLE patients had more systemic side effects of vaccination—although these were all mild. With respect to vaccination efficacy, the authors concluded that “SLE patients appear to have a decreased immune response, compared to healthy controls.”

Using blood samples taken at baseline and at the follow-up visit, the subjects' influenza antibody responses to A/H1N1, A/H3N2, and B/Hong Kong were measured in 3 ways: by assessment of a

Although the GMT increased after vaccination in all subjects and did not differ significantly between patients and controls, the authors suggested this was because prevaccination GMTs were higher in patients than in controls because of the patients' higher rate of vaccination in the previous year (77% vs. 22%).

Compared with controls, SLE patients had significantly fewer seroconversions against A/H1N1 and A/H3N2 (43% vs. 94% and 39% vs. 88%, respectively). SLE patients also had fewer seroconversions to B/Hong Kong, compared with controls (41% vs. 71%), although this difference was marginally significant.

No significant differences could be found overall between patients and controls in terms of the percent of people achieving a postvaccination titer of

After excluding all subjects who had been vaccinated the previous year, they found that significantly fewer SLE patients achieved seroconversions and protective titers to A/H1N1 and A/H3N2. (See seroconversion graph.)

“It is conceivable that SLE patients have an intrinsic [immunologic] defect that results in decreased responsiveness to vaccination,” wrote the authors, adding that the use of immunosuppressive drugs may further decrease the vaccination response in these patients. “SLE patients receiving azathioprine showed a trend towards a decreased immune response against influenza A/H3N2, compared with the other patient groups,” they wrote. “For A/H3N2, SLE patients receiving azathioprine had fewer fourfold titre rises than [did] the other patient groups (P = .041). Furthermore, a smaller proportion of the azathioprine group achieved titres of 40 or greater against A/H3N2 (P = .030), compared with the other patient groups.”(See immune response graph.)

The authors suggested that virosomal vaccines, which generate better cellular immune responses and enhance humoral immune responses, might improve the efficacy of vaccination in SLE patients.

ELSEVIER GLOBAL MEDICAL NEWS

ELSEVIER GLOBAL MEDICAL NEWS

SAN ANTONIO — An intensive home visiting program targeting pregnant women and parents of newborns reduced premature births and significantly improved health care and pediatric health in Hispanic families, according to preliminary results of a study presented by Kimberly Dumont, Ph.D., at the annual meeting of the Society for Prevention Research.

The Healthy Families New York (HFNY) program, which is modeled after the national Healthy Families America initiative, is primarily aimed at preventing child neglect and abuse, said Dr. Dumont, senior research associate with the New York State Office of Children & Family Services in Rensselaer. Home visits are conducted by trained paraprofessionals until children reach age 5 years, with the goal of enhancing parent-child interactions and improving child health and development and parental self-sufficiency.

The study, a collaboration between the Bureau of Evaluation and Research at the Office of Children & Family Services and the Center of Human Services Research of the State University of New York at Albany, included 1,173 Hispanic, African American, and white women. A total of 42% of the sample were included because screening identified them as being at risk for depression, and 9% were included because they had a history of substantiated child abuse or neglect. The remaining 49% were randomly assigned before 31 weeks' gestation.

The subjects were randomized to the HFNY intervention or to a control group that was given information and referrals to other services in the community. Baseline interviews were conducted shortly after randomization, with follow-up interviews at birth and annually up to 3 years post partum in this preliminary report. During these interviews, participants were asked about health insurance, primary care providers, birth outcomes, and child behavior.

Preliminary results up to 2 years post partum show significantly fewer premature babies, better pediatric health care, and less pediatric somatic complaints and behavior problems in Hispanic families receiving the HFNY intervention, compared with Hispanic controls who were offered information and referral only. The intervention did not improve these outcomes in white and African American families. Dr. Dumont speculated that this may demonstrate that the Hispanic population was most in need of this type of intervention because it may reduce the health care disparities between them and non-Hispanic families.

“Hispanic women in the control group were initially well connected to a primary care provider, but this connection weakened over the course of the study,” she said in an interview. By the end of the second year of the study, Hispanic controls were less likely than non-Hispanics to have a primary care provider (relative risk 0.92). In contrast, connection to health care was relatively strong for the non-Hispanic controls throughout the study, resulting in a disparity between the Hispanic and non-Hispanic controls. The HFNY intervention prevented this disparity from emerging, with Hispanic women retaining their connection to a primary care provider (RR 1.06). “HFNY demonstrates particular success in keeping Latina women connected to health care, [which] may promote positive child outcomes,” she said.

There was a reduction in premature births in treated Hispanic women, compared with Hispanic controls in the subgroup of 116 Hispanic women who were randomized before 31 weeks' gestation. Those receiving the HFNY intervention had a 7% rate of premature births, compared with 14% in controls. “Although marginally significant, probably due to the limited sample size, this difference was clinically meaningful,” said Dr. Dumont in an interview.

In addition, using the Child Behavior Checklist, the study found a reduced rate of pediatric somatic and behavior problems in the Hispanic intervention group, compared with Hispanic controls.

For affective problems, the average number of symptoms for Hispanic target children was 2.1, compared with 1.3 in controls. For pervasive developmental problems, the average number of symptoms for target children was 2.3, compared with 3.1 in controls. For attention deficit symptom, the average number of symptoms for target children was 4.4 vs. 5.1 in controls. And for somatic complaints, the average number of symptoms for target children was 0.5 vs. 1 in controls. The HFNY intervention also resulted in improved pediatric health care in the entire study population.

SAN ANTONIO — An intensive home visiting program targeting pregnant women and parents of newborns reduced premature births and significantly improved health care and pediatric health in Hispanic families, according to preliminary results of a study presented by Kimberly Dumont, Ph.D., at the annual meeting of the Society for Prevention Research.

The Healthy Families New York (HFNY) program, which is modeled after the national Healthy Families America initiative, is primarily aimed at preventing child neglect and abuse, said Dr. Dumont, senior research associate with the New York State Office of Children & Family Services in Rensselaer. Home visits are conducted by trained paraprofessionals until children reach age 5 years, with the goal of enhancing parent-child interactions and improving child health and development and parental self-sufficiency.

The study, a collaboration between the Bureau of Evaluation and Research at the Office of Children & Family Services and the Center of Human Services Research of the State University of New York at Albany, included 1,173 Hispanic, African American, and white women. A total of 42% of the sample were included because screening identified them as being at risk for depression, and 9% were included because they had a history of substantiated child abuse or neglect. The remaining 49% were randomly assigned before 31 weeks' gestation.

The subjects were randomized to the HFNY intervention or to a control group that was given information and referrals to other services in the community. Baseline interviews were conducted shortly after randomization, with follow-up interviews at birth and annually up to 3 years post partum in this preliminary report. During these interviews, participants were asked about health insurance, primary care providers, birth outcomes, and child behavior.

Preliminary results up to 2 years post partum show significantly fewer premature babies, better pediatric health care, and less pediatric somatic complaints and behavior problems in Hispanic families receiving the HFNY intervention, compared with Hispanic controls who were offered information and referral only. The intervention did not improve these outcomes in white and African American families. Dr. Dumont speculated that this may demonstrate that the Hispanic population was most in need of this type of intervention because it may reduce the health care disparities between them and non-Hispanic families.

“Hispanic women in the control group were initially well connected to a primary care provider, but this connection weakened over the course of the study,” she said in an interview. By the end of the second year of the study, Hispanic controls were less likely than non-Hispanics to have a primary care provider (relative risk 0.92). In contrast, connection to health care was relatively strong for the non-Hispanic controls throughout the study, resulting in a disparity between the Hispanic and non-Hispanic controls. The HFNY intervention prevented this disparity from emerging, with Hispanic women retaining their connection to a primary care provider (RR 1.06). “HFNY demonstrates particular success in keeping Latina women connected to health care, [which] may promote positive child outcomes,” she said.

There was a reduction in premature births in treated Hispanic women, compared with Hispanic controls in the subgroup of 116 Hispanic women who were randomized before 31 weeks' gestation. Those receiving the HFNY intervention had a 7% rate of premature births, compared with 14% in controls. “Although marginally significant, probably due to the limited sample size, this difference was clinically meaningful,” said Dr. Dumont in an interview.

In addition, using the Child Behavior Checklist, the study found a reduced rate of pediatric somatic and behavior problems in the Hispanic intervention group, compared with Hispanic controls.

For affective problems, the average number of symptoms for Hispanic target children was 2.1, compared with 1.3 in controls. For pervasive developmental problems, the average number of symptoms for target children was 2.3, compared with 3.1 in controls. For attention deficit symptom, the average number of symptoms for target children was 4.4 vs. 5.1 in controls. And for somatic complaints, the average number of symptoms for target children was 0.5 vs. 1 in controls. The HFNY intervention also resulted in improved pediatric health care in the entire study population.

SAN ANTONIO — An intensive home visiting program targeting pregnant women and parents of newborns reduced premature births and significantly improved health care and pediatric health in Hispanic families, according to preliminary results of a study presented by Kimberly Dumont, Ph.D., at the annual meeting of the Society for Prevention Research.

The Healthy Families New York (HFNY) program, which is modeled after the national Healthy Families America initiative, is primarily aimed at preventing child neglect and abuse, said Dr. Dumont, senior research associate with the New York State Office of Children & Family Services in Rensselaer. Home visits are conducted by trained paraprofessionals until children reach age 5 years, with the goal of enhancing parent-child interactions and improving child health and development and parental self-sufficiency.

The study, a collaboration between the Bureau of Evaluation and Research at the Office of Children & Family Services and the Center of Human Services Research of the State University of New York at Albany, included 1,173 Hispanic, African American, and white women. A total of 42% of the sample were included because screening identified them as being at risk for depression, and 9% were included because they had a history of substantiated child abuse or neglect. The remaining 49% were randomly assigned before 31 weeks' gestation.

The subjects were randomized to the HFNY intervention or to a control group that was given information and referrals to other services in the community. Baseline interviews were conducted shortly after randomization, with follow-up interviews at birth and annually up to 3 years post partum in this preliminary report. During these interviews, participants were asked about health insurance, primary care providers, birth outcomes, and child behavior.

Preliminary results up to 2 years post partum show significantly fewer premature babies, better pediatric health care, and less pediatric somatic complaints and behavior problems in Hispanic families receiving the HFNY intervention, compared with Hispanic controls who were offered information and referral only. The intervention did not improve these outcomes in white and African American families. Dr. Dumont speculated that this may demonstrate that the Hispanic population was most in need of this type of intervention because it may reduce the health care disparities between them and non-Hispanic families.

“Hispanic women in the control group were initially well connected to a primary care provider, but this connection weakened over the course of the study,” she said in an interview. By the end of the second year of the study, Hispanic controls were less likely than non-Hispanics to have a primary care provider (relative risk 0.92). In contrast, connection to health care was relatively strong for the non-Hispanic controls throughout the study, resulting in a disparity between the Hispanic and non-Hispanic controls. The HFNY intervention prevented this disparity from emerging, with Hispanic women retaining their connection to a primary care provider (RR 1.06). “HFNY demonstrates particular success in keeping Latina women connected to health care, [which] may promote positive child outcomes,” she said.

There was a reduction in premature births in treated Hispanic women, compared with Hispanic controls in the subgroup of 116 Hispanic women who were randomized before 31 weeks' gestation. Those receiving the HFNY intervention had a 7% rate of premature births, compared with 14% in controls. “Although marginally significant, probably due to the limited sample size, this difference was clinically meaningful,” said Dr. Dumont in an interview.

In addition, using the Child Behavior Checklist, the study found a reduced rate of pediatric somatic and behavior problems in the Hispanic intervention group, compared with Hispanic controls.

For affective problems, the average number of symptoms for Hispanic target children was 2.1, compared with 1.3 in controls. For pervasive developmental problems, the average number of symptoms for target children was 2.3, compared with 3.1 in controls. For attention deficit symptom, the average number of symptoms for target children was 4.4 vs. 5.1 in controls. And for somatic complaints, the average number of symptoms for target children was 0.5 vs. 1 in controls. The HFNY intervention also resulted in improved pediatric health care in the entire study population.

PRAGUE — Women with severely diminished ovarian reserve can experience dramatic improvements in ovarian function, pregnancy rates, and euploidy rates when treated with dehydroepiandrosterone, Dr. Norbert Gleicher stated at the annual meeting of the European Society of Human Reproduction and Embryology.

“We have very small numbers that we are presenting with great caution, but the benefits of DHEA are beginning to become apparent,” said Dr. Gleicher, who practices at a fertility center in New York. “Over 90% of our DHEA patients … are not only women with diminished ovarian reserve, they are women with horribly diminished ovarian reserve—and still we have a third of them getting pregnant.”

Several studies he presented at the meeting suggest that in women with diminished ovarian reserve, DHEA—a mild androgen supplement, given at a dosage of 25 mg three times a day—can improve spontaneous conception rates and in vitro fertilization (IVF) outcomes. “It seems to improve not just quantity but quality of oocytes,” he said in an interview.

In a case study published last year, he and his colleagues reported on their first experience with using DHEA in the context of IVF (Fertil. Steril. 2005;84:756.e1–3). A 42-year-old woman with diminished ovarian reserve began taking the supplement without the physicians' knowledge during her IVF treatment. Before she started taking DHEA, the woman's estradiol level was 1,211 pmol/mL, but it rose to more than 18,000 pmol/mL after 7 months of DHEA treatment. The patient underwent eight subsequent IVF cycles with DHEA treatment, resulting in a dramatic improvement in ovarian response and a total of 66 embryos. She did not get pregnant because she did not have any embryos transferred, choosing to cryopreserve them for future use, he said.

In another study, now in press, they compared 23 IVF patients before and after treatment with DHEA and noted a significant increase in fertilized oocytes after patients were treated (39% vs. 67%). “We did not look at pregnancy rates in this study because the numbers were too small, but this study confirms that DHEA improves egg and embryo numbers and egg and embryo quality,” he said.

A separate study comparing 88 DHEA-treated IVF patients with 99 controls (IVF patients not treated with DHEA) found higher clinical pregnancy rates (27% vs. 9%) and higher implantation rates (9% vs. 3%) in the treated group. The study also found that preimplantation genetic diagnosis performed on the patients' embryos identified a significantly higher rate of aneuploidy in the non-DHEA-treated embryos (78%), compared with that of the treated embryos (57%), he added.

IVF treatment with DHEA in his fertility center involves 4 months of DHEA prior to IVF, during which time he has noted “an unexpectedly large number of spontaneous conceptions,” within the first 2 months of DHEA treatment, he said.

PRAGUE — Women with severely diminished ovarian reserve can experience dramatic improvements in ovarian function, pregnancy rates, and euploidy rates when treated with dehydroepiandrosterone, Dr. Norbert Gleicher stated at the annual meeting of the European Society of Human Reproduction and Embryology.

“We have very small numbers that we are presenting with great caution, but the benefits of DHEA are beginning to become apparent,” said Dr. Gleicher, who practices at a fertility center in New York. “Over 90% of our DHEA patients … are not only women with diminished ovarian reserve, they are women with horribly diminished ovarian reserve—and still we have a third of them getting pregnant.”

Several studies he presented at the meeting suggest that in women with diminished ovarian reserve, DHEA—a mild androgen supplement, given at a dosage of 25 mg three times a day—can improve spontaneous conception rates and in vitro fertilization (IVF) outcomes. “It seems to improve not just quantity but quality of oocytes,” he said in an interview.

In a case study published last year, he and his colleagues reported on their first experience with using DHEA in the context of IVF (Fertil. Steril. 2005;84:756.e1–3). A 42-year-old woman with diminished ovarian reserve began taking the supplement without the physicians' knowledge during her IVF treatment. Before she started taking DHEA, the woman's estradiol level was 1,211 pmol/mL, but it rose to more than 18,000 pmol/mL after 7 months of DHEA treatment. The patient underwent eight subsequent IVF cycles with DHEA treatment, resulting in a dramatic improvement in ovarian response and a total of 66 embryos. She did not get pregnant because she did not have any embryos transferred, choosing to cryopreserve them for future use, he said.

In another study, now in press, they compared 23 IVF patients before and after treatment with DHEA and noted a significant increase in fertilized oocytes after patients were treated (39% vs. 67%). “We did not look at pregnancy rates in this study because the numbers were too small, but this study confirms that DHEA improves egg and embryo numbers and egg and embryo quality,” he said.

A separate study comparing 88 DHEA-treated IVF patients with 99 controls (IVF patients not treated with DHEA) found higher clinical pregnancy rates (27% vs. 9%) and higher implantation rates (9% vs. 3%) in the treated group. The study also found that preimplantation genetic diagnosis performed on the patients' embryos identified a significantly higher rate of aneuploidy in the non-DHEA-treated embryos (78%), compared with that of the treated embryos (57%), he added.

IVF treatment with DHEA in his fertility center involves 4 months of DHEA prior to IVF, during which time he has noted “an unexpectedly large number of spontaneous conceptions,” within the first 2 months of DHEA treatment, he said.

PRAGUE — Women with severely diminished ovarian reserve can experience dramatic improvements in ovarian function, pregnancy rates, and euploidy rates when treated with dehydroepiandrosterone, Dr. Norbert Gleicher stated at the annual meeting of the European Society of Human Reproduction and Embryology.

“We have very small numbers that we are presenting with great caution, but the benefits of DHEA are beginning to become apparent,” said Dr. Gleicher, who practices at a fertility center in New York. “Over 90% of our DHEA patients … are not only women with diminished ovarian reserve, they are women with horribly diminished ovarian reserve—and still we have a third of them getting pregnant.”

Several studies he presented at the meeting suggest that in women with diminished ovarian reserve, DHEA—a mild androgen supplement, given at a dosage of 25 mg three times a day—can improve spontaneous conception rates and in vitro fertilization (IVF) outcomes. “It seems to improve not just quantity but quality of oocytes,” he said in an interview.

In a case study published last year, he and his colleagues reported on their first experience with using DHEA in the context of IVF (Fertil. Steril. 2005;84:756.e1–3). A 42-year-old woman with diminished ovarian reserve began taking the supplement without the physicians' knowledge during her IVF treatment. Before she started taking DHEA, the woman's estradiol level was 1,211 pmol/mL, but it rose to more than 18,000 pmol/mL after 7 months of DHEA treatment. The patient underwent eight subsequent IVF cycles with DHEA treatment, resulting in a dramatic improvement in ovarian response and a total of 66 embryos. She did not get pregnant because she did not have any embryos transferred, choosing to cryopreserve them for future use, he said.

In another study, now in press, they compared 23 IVF patients before and after treatment with DHEA and noted a significant increase in fertilized oocytes after patients were treated (39% vs. 67%). “We did not look at pregnancy rates in this study because the numbers were too small, but this study confirms that DHEA improves egg and embryo numbers and egg and embryo quality,” he said.

A separate study comparing 88 DHEA-treated IVF patients with 99 controls (IVF patients not treated with DHEA) found higher clinical pregnancy rates (27% vs. 9%) and higher implantation rates (9% vs. 3%) in the treated group. The study also found that preimplantation genetic diagnosis performed on the patients' embryos identified a significantly higher rate of aneuploidy in the non-DHEA-treated embryos (78%), compared with that of the treated embryos (57%), he added.

IVF treatment with DHEA in his fertility center involves 4 months of DHEA prior to IVF, during which time he has noted “an unexpectedly large number of spontaneous conceptions,” within the first 2 months of DHEA treatment, he said.

PRAGUE — Genetic carriers of familial adenomatous polyposis can now decrease their risks of conceiving an affected child with the help of preimplantation genetic diagnosis, Stéphane Viville, Ph.D., reported at the annual meeting of the European Society of Human Reproduction and Embryology.

Until now, couples in whom one person was a dominant carrier of this adult-onset colorectal cancer had to wait for prenatal tests to confirm an affected pregnancy and then make the decision about termination.

Dr. Viville of University Hospital in Strasbourg, France, studied 15 couples (7 female carriers and 8 male carriers) who were at risk of conceiving a child with familial adenomatous polyposis. Although 13% of the couples already had children, none had any knowledge of their children's carrier status. The couples underwent in vitro fertilization. Using a fluorescent polymerase chain reaction technique, Dr. Viville's team identified and excluded affected embryos. A total of 12 cycles and 11 retrievals were performed. Eight embryos were replaced, with the result of one healthy delivery and two ongoing pregnancies, he reported.

PRAGUE — Genetic carriers of familial adenomatous polyposis can now decrease their risks of conceiving an affected child with the help of preimplantation genetic diagnosis, Stéphane Viville, Ph.D., reported at the annual meeting of the European Society of Human Reproduction and Embryology.

Until now, couples in whom one person was a dominant carrier of this adult-onset colorectal cancer had to wait for prenatal tests to confirm an affected pregnancy and then make the decision about termination.

Dr. Viville of University Hospital in Strasbourg, France, studied 15 couples (7 female carriers and 8 male carriers) who were at risk of conceiving a child with familial adenomatous polyposis. Although 13% of the couples already had children, none had any knowledge of their children's carrier status. The couples underwent in vitro fertilization. Using a fluorescent polymerase chain reaction technique, Dr. Viville's team identified and excluded affected embryos. A total of 12 cycles and 11 retrievals were performed. Eight embryos were replaced, with the result of one healthy delivery and two ongoing pregnancies, he reported.

PRAGUE — Genetic carriers of familial adenomatous polyposis can now decrease their risks of conceiving an affected child with the help of preimplantation genetic diagnosis, Stéphane Viville, Ph.D., reported at the annual meeting of the European Society of Human Reproduction and Embryology.

Until now, couples in whom one person was a dominant carrier of this adult-onset colorectal cancer had to wait for prenatal tests to confirm an affected pregnancy and then make the decision about termination.

Dr. Viville of University Hospital in Strasbourg, France, studied 15 couples (7 female carriers and 8 male carriers) who were at risk of conceiving a child with familial adenomatous polyposis. Although 13% of the couples already had children, none had any knowledge of their children's carrier status. The couples underwent in vitro fertilization. Using a fluorescent polymerase chain reaction technique, Dr. Viville's team identified and excluded affected embryos. A total of 12 cycles and 11 retrievals were performed. Eight embryos were replaced, with the result of one healthy delivery and two ongoing pregnancies, he reported.

BOSTON — New studies showing conflicting results on the effect of fish oil on the heart add weight to the notion that perhaps age and health status influence whether omega-3 fatty acids prevent or promote cardiac arrhythmias, according to Dr. Anthony Aizer.

His study, which he presented at the annual meeting of the Heart Rhythm Society, linked increased fish consumption with a higher risk of developing atrial fibrillation (AF) in healthy male physicians (aged 40–84 years) who were enrolled in the previously reported Physicians' Health Study (N. Engl. J. Med. 1989;321:129–35).

The findings corroborate recently published results from the Danish Diet, Cancer, and Health study (Am. J. Clin. Nutr. 2005;81:50–4), but contrast with data from the Cardiovascular Health study (Circulation 2004;110:368–73), said Dr. Aizer, who is an electrophysiologist at New York University Medical Center. He said one explanation for the conflicting findings could be that fish oil may have profibrillatory effects in healthy individuals but antifibrillatory effects in subjects with preexisting cardiovascular disease (CVD).

“One hypothesis is that omega-3 fatty acids have some effects on the autonomic nervous system—in particular, by increasing parasympathetic tone. In generally healthy individuals without CVD, it is sometimes thought that an increase in autonomic tone may play a role in the development of AF,” he said in an interview. “In contrast, in older, less healthy individuals it's possible that other effects are more significant. In certain individuals, the effect of omega-3 fatty acids that enhance cardiac tissue refractoriness may have a more significant impact, thereby preventing AF.”

Dr. Aizer's analysis of the Physicians' Health Study included 17,679 men who had completed a fish consumption questionnaire in 1983 and of whom 7% reported AF 15 years later. He found that men who reported eating five or more fish meals per week had a 55% higher rate of AF, compared with men who ate fish only once a month.

But two other smaller studies that were presented as posters at the meeting reported the cardiac benefits of omega-3 fatty acids.

A prospective study of six patients with paroxysmal AF showed that an infusion of 100 mL of omega-3 fatty acids resulted in an increase in atrial refractoriness, a reduction in AF inducibility, and a prolongation of fibrillatory cycle length, reported Dr. Hercules E. Mavrakis, from Heraklion University Hospital in Crete, Greece.

And another study of 26 patients with inducible ventricular tachycardia (VT) at 3 or more months post MI showed strong benefits of oral omega-3 fatty acid capsules (180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid) daily, compared with placebo, over a 40-day treatment period, reported Dr. Glenn D. Young from the Cardiovascular Research Centre in Adelaide, Australia.

At the end of the study, VT was no longer inducible in 5 of the 12 treated patients, and 5 of the remaining 7 patients required more aggressive stimulation to induce arrhythmia. By contrast, in the 14 control patients, VT was no longer inducible in only 1 patient, and 3 of the remaining 13 patients required more aggressive inducement.

“Statistically, it was a very significant result. There seems to be a direct effect of fish oil in preventing ventricular tachycardia,” said Dr. Young in an interview. “People can achieve that level with only [two or three] oily fish meals a week.”

Dr. Aizer's finding of a higher incidence of AF with increased fish consumption cannot be interpreted as causal. “This wasn't a randomized, controlled trial [of fish consumption]—there could always be an association of fish with some other factor that's causing the atrial fibrillation,” he said.

BOSTON — New studies showing conflicting results on the effect of fish oil on the heart add weight to the notion that perhaps age and health status influence whether omega-3 fatty acids prevent or promote cardiac arrhythmias, according to Dr. Anthony Aizer.

His study, which he presented at the annual meeting of the Heart Rhythm Society, linked increased fish consumption with a higher risk of developing atrial fibrillation (AF) in healthy male physicians (aged 40–84 years) who were enrolled in the previously reported Physicians' Health Study (N. Engl. J. Med. 1989;321:129–35).

The findings corroborate recently published results from the Danish Diet, Cancer, and Health study (Am. J. Clin. Nutr. 2005;81:50–4), but contrast with data from the Cardiovascular Health study (Circulation 2004;110:368–73), said Dr. Aizer, who is an electrophysiologist at New York University Medical Center. He said one explanation for the conflicting findings could be that fish oil may have profibrillatory effects in healthy individuals but antifibrillatory effects in subjects with preexisting cardiovascular disease (CVD).

“One hypothesis is that omega-3 fatty acids have some effects on the autonomic nervous system—in particular, by increasing parasympathetic tone. In generally healthy individuals without CVD, it is sometimes thought that an increase in autonomic tone may play a role in the development of AF,” he said in an interview. “In contrast, in older, less healthy individuals it's possible that other effects are more significant. In certain individuals, the effect of omega-3 fatty acids that enhance cardiac tissue refractoriness may have a more significant impact, thereby preventing AF.”

Dr. Aizer's analysis of the Physicians' Health Study included 17,679 men who had completed a fish consumption questionnaire in 1983 and of whom 7% reported AF 15 years later. He found that men who reported eating five or more fish meals per week had a 55% higher rate of AF, compared with men who ate fish only once a month.

But two other smaller studies that were presented as posters at the meeting reported the cardiac benefits of omega-3 fatty acids.

A prospective study of six patients with paroxysmal AF showed that an infusion of 100 mL of omega-3 fatty acids resulted in an increase in atrial refractoriness, a reduction in AF inducibility, and a prolongation of fibrillatory cycle length, reported Dr. Hercules E. Mavrakis, from Heraklion University Hospital in Crete, Greece.

And another study of 26 patients with inducible ventricular tachycardia (VT) at 3 or more months post MI showed strong benefits of oral omega-3 fatty acid capsules (180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid) daily, compared with placebo, over a 40-day treatment period, reported Dr. Glenn D. Young from the Cardiovascular Research Centre in Adelaide, Australia.

At the end of the study, VT was no longer inducible in 5 of the 12 treated patients, and 5 of the remaining 7 patients required more aggressive stimulation to induce arrhythmia. By contrast, in the 14 control patients, VT was no longer inducible in only 1 patient, and 3 of the remaining 13 patients required more aggressive inducement.

“Statistically, it was a very significant result. There seems to be a direct effect of fish oil in preventing ventricular tachycardia,” said Dr. Young in an interview. “People can achieve that level with only [two or three] oily fish meals a week.”

Dr. Aizer's finding of a higher incidence of AF with increased fish consumption cannot be interpreted as causal. “This wasn't a randomized, controlled trial [of fish consumption]—there could always be an association of fish with some other factor that's causing the atrial fibrillation,” he said.

BOSTON — New studies showing conflicting results on the effect of fish oil on the heart add weight to the notion that perhaps age and health status influence whether omega-3 fatty acids prevent or promote cardiac arrhythmias, according to Dr. Anthony Aizer.

His study, which he presented at the annual meeting of the Heart Rhythm Society, linked increased fish consumption with a higher risk of developing atrial fibrillation (AF) in healthy male physicians (aged 40–84 years) who were enrolled in the previously reported Physicians' Health Study (N. Engl. J. Med. 1989;321:129–35).

The findings corroborate recently published results from the Danish Diet, Cancer, and Health study (Am. J. Clin. Nutr. 2005;81:50–4), but contrast with data from the Cardiovascular Health study (Circulation 2004;110:368–73), said Dr. Aizer, who is an electrophysiologist at New York University Medical Center. He said one explanation for the conflicting findings could be that fish oil may have profibrillatory effects in healthy individuals but antifibrillatory effects in subjects with preexisting cardiovascular disease (CVD).

“One hypothesis is that omega-3 fatty acids have some effects on the autonomic nervous system—in particular, by increasing parasympathetic tone. In generally healthy individuals without CVD, it is sometimes thought that an increase in autonomic tone may play a role in the development of AF,” he said in an interview. “In contrast, in older, less healthy individuals it's possible that other effects are more significant. In certain individuals, the effect of omega-3 fatty acids that enhance cardiac tissue refractoriness may have a more significant impact, thereby preventing AF.”

Dr. Aizer's analysis of the Physicians' Health Study included 17,679 men who had completed a fish consumption questionnaire in 1983 and of whom 7% reported AF 15 years later. He found that men who reported eating five or more fish meals per week had a 55% higher rate of AF, compared with men who ate fish only once a month.

But two other smaller studies that were presented as posters at the meeting reported the cardiac benefits of omega-3 fatty acids.

A prospective study of six patients with paroxysmal AF showed that an infusion of 100 mL of omega-3 fatty acids resulted in an increase in atrial refractoriness, a reduction in AF inducibility, and a prolongation of fibrillatory cycle length, reported Dr. Hercules E. Mavrakis, from Heraklion University Hospital in Crete, Greece.

And another study of 26 patients with inducible ventricular tachycardia (VT) at 3 or more months post MI showed strong benefits of oral omega-3 fatty acid capsules (180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid) daily, compared with placebo, over a 40-day treatment period, reported Dr. Glenn D. Young from the Cardiovascular Research Centre in Adelaide, Australia.

At the end of the study, VT was no longer inducible in 5 of the 12 treated patients, and 5 of the remaining 7 patients required more aggressive stimulation to induce arrhythmia. By contrast, in the 14 control patients, VT was no longer inducible in only 1 patient, and 3 of the remaining 13 patients required more aggressive inducement.

“Statistically, it was a very significant result. There seems to be a direct effect of fish oil in preventing ventricular tachycardia,” said Dr. Young in an interview. “People can achieve that level with only [two or three] oily fish meals a week.”

Dr. Aizer's finding of a higher incidence of AF with increased fish consumption cannot be interpreted as causal. “This wasn't a randomized, controlled trial [of fish consumption]—there could always be an association of fish with some other factor that's causing the atrial fibrillation,” he said.

BOSTON — Although industry officials appeared to embrace proposed guidelines from the Heart Rhythm Society aimed at improving postmarket surveillance and the performance of implantable heart devices, the reaction of the Food and Drug Administration was more guarded during a Town Hall Meeting hosted by the society at its annual meeting.

“I was not particularly encouraged by the FDA's comments,” remarked Dr. Robert G. Hauser, a member of the Heart Rhythm Society (HRS) task force that drafted the proposed guidelines, and a senior consultant cardiologist at the Minneapolis Heart Institute.

The guideline's intent is to improve both the detection of device malfunctions and the communication of their clinical significance to physicians and patients. The guidelines were released in April; the society plans to publish the final recommendations in October.

Broadly speaking, the guidelines advocate improved transparency in the industry's postmarket monitoring and reporting of device malfunctions in pacemakers and implantable cardioverter defibrillators (ICDs) and their components; the establishment of new systems to identify malfunctioning devices more quickly; and a standard process of notification and communication from manufacturers to patients and physicians in the event of device malfunction.

More specifically, HRS recommends that the industry and the FDA abandon the term “recall”—replacing it with “advisory”—because it is misleading and can cause undue alarm in patients. “It frightens patients, and it is inaccurate,” said Dr. Hauser in an interview. “Until they get in to see the physician, they are under the impression that they have to have their device removed and returned to the manufacturer.”

But the suggestion met with FDA resistance. “Recall nomenclature is deeply embedded in FDA regulations and operations and cannot be changed quickly,” said the FDA's Dr. Bram D. Zuckerman, director of the division of cardiovascular devices in the Center for Devices and Radiological Health.

“They're reluctant because this terminology applies to all the medical devices they oversee,” Dr. Leslie A. Saxon, professor of medicine at University of Southern California, Los Angeles, said in an interview. But with roughly 200,000 ICDs falling under the “recall” terminology in the past 12–18 months, and driving an arguably inflated 20% explantation rate, the terminology deserves reconsideration.

For physicians, the guidelines suggest informing patients not only of device therapy's benefits and risks, but also about device and component performance and expected malfunction rates both at initial implantation and replacement.

Furthermore, physicians should consider, when appropriate, alternatives to device explantation, such as reprogramming or enhanced monitoring.

Physicians are also encouraged to enhance surveillance by obtaining patient or family consent for the return of all devices to the manufacturer after explantation—even when malfunction is not suspected—or, when this is not possible, to attempt postmortem device interrogation. The society also noted that physicians should be adequately compensated for their time and effort in the postmortem evaluation and reporting process, and that CPT codes should be set for these activities.

For manufacturers, the society recommended they set standards for device and component performance, and provide regular, unbiased reports on malfunction rates for each device in a user-friendly format that is easily accessible by physicians, health care givers, and patients.

The HRS recommendations also call for an independent advisory committee for industry, made up of medical experts in the field. Such a committee would meet regularly but also in response to specific malfunction reports, and would advise the industry on how to inform physicians and the public.

Manufacturers should communicate the committee findings on malfunctions and performance first to physicians and then directly to patients by using standard communication forms, said the HRS recommendation.

Direct communication to patients is a controversial idea, acknowledged Dr. Saxon, but it fits with the times. “It's an information age. People want to know and I don't blame them.”

Timothy S. Samsel, vice president of regulatory affairs for Medtronic Inc., said companies support the notion of an independent advisory panel but acknowledged that the panel's independence could be questioned because panelists would be compensated, would be asked to sign a contract of confidentiality, and could potentially have their advice ignored by the company.

“I think that would be a rare event,” commented Dr. Hauser. “If a group of experts makes a recommendation and the company decides to ignore it, they would be going down a separate path—and I don't think you would see that kind of thing happening.”

The FDA's Dr. Zuckerman says his agency has already begun to establish a postmarket advisory panel and has appointed Dr. William H. Maisel of Beth Israel Deaconess Medical Center, Boston, as chairman.

HRS also recommended that the FDA enhance its Manufacturer and User Facility Device Experience (MAUDE) database by devising a form that would allow for specific reporting on ICD/pacemaker events.

The proposed guidelines are available at www.hrsonline.org

BOSTON — Although industry officials appeared to embrace proposed guidelines from the Heart Rhythm Society aimed at improving postmarket surveillance and the performance of implantable heart devices, the reaction of the Food and Drug Administration was more guarded during a Town Hall Meeting hosted by the society at its annual meeting.

“I was not particularly encouraged by the FDA's comments,” remarked Dr. Robert G. Hauser, a member of the Heart Rhythm Society (HRS) task force that drafted the proposed guidelines, and a senior consultant cardiologist at the Minneapolis Heart Institute.

The guideline's intent is to improve both the detection of device malfunctions and the communication of their clinical significance to physicians and patients. The guidelines were released in April; the society plans to publish the final recommendations in October.

Broadly speaking, the guidelines advocate improved transparency in the industry's postmarket monitoring and reporting of device malfunctions in pacemakers and implantable cardioverter defibrillators (ICDs) and their components; the establishment of new systems to identify malfunctioning devices more quickly; and a standard process of notification and communication from manufacturers to patients and physicians in the event of device malfunction.

More specifically, HRS recommends that the industry and the FDA abandon the term “recall”—replacing it with “advisory”—because it is misleading and can cause undue alarm in patients. “It frightens patients, and it is inaccurate,” said Dr. Hauser in an interview. “Until they get in to see the physician, they are under the impression that they have to have their device removed and returned to the manufacturer.”

But the suggestion met with FDA resistance. “Recall nomenclature is deeply embedded in FDA regulations and operations and cannot be changed quickly,” said the FDA's Dr. Bram D. Zuckerman, director of the division of cardiovascular devices in the Center for Devices and Radiological Health.

“They're reluctant because this terminology applies to all the medical devices they oversee,” Dr. Leslie A. Saxon, professor of medicine at University of Southern California, Los Angeles, said in an interview. But with roughly 200,000 ICDs falling under the “recall” terminology in the past 12–18 months, and driving an arguably inflated 20% explantation rate, the terminology deserves reconsideration.

For physicians, the guidelines suggest informing patients not only of device therapy's benefits and risks, but also about device and component performance and expected malfunction rates both at initial implantation and replacement.

Furthermore, physicians should consider, when appropriate, alternatives to device explantation, such as reprogramming or enhanced monitoring.

Physicians are also encouraged to enhance surveillance by obtaining patient or family consent for the return of all devices to the manufacturer after explantation—even when malfunction is not suspected—or, when this is not possible, to attempt postmortem device interrogation. The society also noted that physicians should be adequately compensated for their time and effort in the postmortem evaluation and reporting process, and that CPT codes should be set for these activities.

For manufacturers, the society recommended they set standards for device and component performance, and provide regular, unbiased reports on malfunction rates for each device in a user-friendly format that is easily accessible by physicians, health care givers, and patients.

The HRS recommendations also call for an independent advisory committee for industry, made up of medical experts in the field. Such a committee would meet regularly but also in response to specific malfunction reports, and would advise the industry on how to inform physicians and the public.

Manufacturers should communicate the committee findings on malfunctions and performance first to physicians and then directly to patients by using standard communication forms, said the HRS recommendation.

Direct communication to patients is a controversial idea, acknowledged Dr. Saxon, but it fits with the times. “It's an information age. People want to know and I don't blame them.”

Timothy S. Samsel, vice president of regulatory affairs for Medtronic Inc., said companies support the notion of an independent advisory panel but acknowledged that the panel's independence could be questioned because panelists would be compensated, would be asked to sign a contract of confidentiality, and could potentially have their advice ignored by the company.

“I think that would be a rare event,” commented Dr. Hauser. “If a group of experts makes a recommendation and the company decides to ignore it, they would be going down a separate path—and I don't think you would see that kind of thing happening.”

The FDA's Dr. Zuckerman says his agency has already begun to establish a postmarket advisory panel and has appointed Dr. William H. Maisel of Beth Israel Deaconess Medical Center, Boston, as chairman.

HRS also recommended that the FDA enhance its Manufacturer and User Facility Device Experience (MAUDE) database by devising a form that would allow for specific reporting on ICD/pacemaker events.

The proposed guidelines are available at www.hrsonline.org

BOSTON — Although industry officials appeared to embrace proposed guidelines from the Heart Rhythm Society aimed at improving postmarket surveillance and the performance of implantable heart devices, the reaction of the Food and Drug Administration was more guarded during a Town Hall Meeting hosted by the society at its annual meeting.

“I was not particularly encouraged by the FDA's comments,” remarked Dr. Robert G. Hauser, a member of the Heart Rhythm Society (HRS) task force that drafted the proposed guidelines, and a senior consultant cardiologist at the Minneapolis Heart Institute.

The guideline's intent is to improve both the detection of device malfunctions and the communication of their clinical significance to physicians and patients. The guidelines were released in April; the society plans to publish the final recommendations in October.

Broadly speaking, the guidelines advocate improved transparency in the industry's postmarket monitoring and reporting of device malfunctions in pacemakers and implantable cardioverter defibrillators (ICDs) and their components; the establishment of new systems to identify malfunctioning devices more quickly; and a standard process of notification and communication from manufacturers to patients and physicians in the event of device malfunction.

More specifically, HRS recommends that the industry and the FDA abandon the term “recall”—replacing it with “advisory”—because it is misleading and can cause undue alarm in patients. “It frightens patients, and it is inaccurate,” said Dr. Hauser in an interview. “Until they get in to see the physician, they are under the impression that they have to have their device removed and returned to the manufacturer.”

But the suggestion met with FDA resistance. “Recall nomenclature is deeply embedded in FDA regulations and operations and cannot be changed quickly,” said the FDA's Dr. Bram D. Zuckerman, director of the division of cardiovascular devices in the Center for Devices and Radiological Health.

“They're reluctant because this terminology applies to all the medical devices they oversee,” Dr. Leslie A. Saxon, professor of medicine at University of Southern California, Los Angeles, said in an interview. But with roughly 200,000 ICDs falling under the “recall” terminology in the past 12–18 months, and driving an arguably inflated 20% explantation rate, the terminology deserves reconsideration.

For physicians, the guidelines suggest informing patients not only of device therapy's benefits and risks, but also about device and component performance and expected malfunction rates both at initial implantation and replacement.

Furthermore, physicians should consider, when appropriate, alternatives to device explantation, such as reprogramming or enhanced monitoring.

Physicians are also encouraged to enhance surveillance by obtaining patient or family consent for the return of all devices to the manufacturer after explantation—even when malfunction is not suspected—or, when this is not possible, to attempt postmortem device interrogation. The society also noted that physicians should be adequately compensated for their time and effort in the postmortem evaluation and reporting process, and that CPT codes should be set for these activities.

For manufacturers, the society recommended they set standards for device and component performance, and provide regular, unbiased reports on malfunction rates for each device in a user-friendly format that is easily accessible by physicians, health care givers, and patients.

The HRS recommendations also call for an independent advisory committee for industry, made up of medical experts in the field. Such a committee would meet regularly but also in response to specific malfunction reports, and would advise the industry on how to inform physicians and the public.

Manufacturers should communicate the committee findings on malfunctions and performance first to physicians and then directly to patients by using standard communication forms, said the HRS recommendation.

Direct communication to patients is a controversial idea, acknowledged Dr. Saxon, but it fits with the times. “It's an information age. People want to know and I don't blame them.”

Timothy S. Samsel, vice president of regulatory affairs for Medtronic Inc., said companies support the notion of an independent advisory panel but acknowledged that the panel's independence could be questioned because panelists would be compensated, would be asked to sign a contract of confidentiality, and could potentially have their advice ignored by the company.

“I think that would be a rare event,” commented Dr. Hauser. “If a group of experts makes a recommendation and the company decides to ignore it, they would be going down a separate path—and I don't think you would see that kind of thing happening.”

The FDA's Dr. Zuckerman says his agency has already begun to establish a postmarket advisory panel and has appointed Dr. William H. Maisel of Beth Israel Deaconess Medical Center, Boston, as chairman.

HRS also recommended that the FDA enhance its Manufacturer and User Facility Device Experience (MAUDE) database by devising a form that would allow for specific reporting on ICD/pacemaker events.

The proposed guidelines are available at www.hrsonline.org

SAN ANTONIO – The thought of the high school transition is enough to reduce boys' academic effort and performance–whereas for girls, it has no impact on those measures, according to a study presented at the annual meeting of the Society for Prevention Research.

“Boys' self-concepts are more focused on autonomy and social power, whereas girls' self-concepts are more focused on intimate personal relationships. We thought that thinking about going to high school would lead boys to think about how people wouldn't know them, and how teachers would be more strict, and that would lead them to disengage academically,” said lead investigator Daniel Brickman of the psychology department at the University of Michigan, Ann Arbor.

His study included 59 eighth-grade students (32 female). Subjects were randomized to one of three groups. Those in the first group were primed for high school with a message of continuity: “In many ways starting high school is not really that much of a big change. … List three ways in which next year will be similar to this year.” In the second group, subjects were primed with a message of change: “In many ways starting high school is a big change. … List three ways in which next year will be different from this year.” The third group received no priming.

All three groups were then asked to complete written exercises that measured current academic effort, future effort, and willingness to engage.

The study found that priming boys for the transition to high school undermined their academic effort and performance–regardless of whether the prime emphasized constancy or change. In contrast, priming girls did not affect their effort and performance.

Prior research indicates that secondary schools present increased competition for positions of social power and fewer opportunities to express autonomy, compared with primary schools. “This squelching of power and autonomy might be especially detrimental for boys,” Mr. Brickman said in an interview.

“It seems like it's not so helpful to focus on the transition to high school without focusing on something else as well,” he added. In his next study, he hopes to prime boys with the idea that high school will promote autonomy and social power to see whether this message prevents their academic decline.

SAN ANTONIO – The thought of the high school transition is enough to reduce boys' academic effort and performance–whereas for girls, it has no impact on those measures, according to a study presented at the annual meeting of the Society for Prevention Research.

“Boys' self-concepts are more focused on autonomy and social power, whereas girls' self-concepts are more focused on intimate personal relationships. We thought that thinking about going to high school would lead boys to think about how people wouldn't know them, and how teachers would be more strict, and that would lead them to disengage academically,” said lead investigator Daniel Brickman of the psychology department at the University of Michigan, Ann Arbor.

His study included 59 eighth-grade students (32 female). Subjects were randomized to one of three groups. Those in the first group were primed for high school with a message of continuity: “In many ways starting high school is not really that much of a big change. … List three ways in which next year will be similar to this year.” In the second group, subjects were primed with a message of change: “In many ways starting high school is a big change. … List three ways in which next year will be different from this year.” The third group received no priming.

All three groups were then asked to complete written exercises that measured current academic effort, future effort, and willingness to engage.

The study found that priming boys for the transition to high school undermined their academic effort and performance–regardless of whether the prime emphasized constancy or change. In contrast, priming girls did not affect their effort and performance.

Prior research indicates that secondary schools present increased competition for positions of social power and fewer opportunities to express autonomy, compared with primary schools. “This squelching of power and autonomy might be especially detrimental for boys,” Mr. Brickman said in an interview.

“It seems like it's not so helpful to focus on the transition to high school without focusing on something else as well,” he added. In his next study, he hopes to prime boys with the idea that high school will promote autonomy and social power to see whether this message prevents their academic decline.

SAN ANTONIO – The thought of the high school transition is enough to reduce boys' academic effort and performance–whereas for girls, it has no impact on those measures, according to a study presented at the annual meeting of the Society for Prevention Research.

“Boys' self-concepts are more focused on autonomy and social power, whereas girls' self-concepts are more focused on intimate personal relationships. We thought that thinking about going to high school would lead boys to think about how people wouldn't know them, and how teachers would be more strict, and that would lead them to disengage academically,” said lead investigator Daniel Brickman of the psychology department at the University of Michigan, Ann Arbor.

His study included 59 eighth-grade students (32 female). Subjects were randomized to one of three groups. Those in the first group were primed for high school with a message of continuity: “In many ways starting high school is not really that much of a big change. … List three ways in which next year will be similar to this year.” In the second group, subjects were primed with a message of change: “In many ways starting high school is a big change. … List three ways in which next year will be different from this year.” The third group received no priming.

All three groups were then asked to complete written exercises that measured current academic effort, future effort, and willingness to engage.

The study found that priming boys for the transition to high school undermined their academic effort and performance–regardless of whether the prime emphasized constancy or change. In contrast, priming girls did not affect their effort and performance.

Prior research indicates that secondary schools present increased competition for positions of social power and fewer opportunities to express autonomy, compared with primary schools. “This squelching of power and autonomy might be especially detrimental for boys,” Mr. Brickman said in an interview.

“It seems like it's not so helpful to focus on the transition to high school without focusing on something else as well,” he added. In his next study, he hopes to prime boys with the idea that high school will promote autonomy and social power to see whether this message prevents their academic decline.