Kate Johnson

With proper informed consent, the prescription of progesterone to prevent preterm birth in appropriate patients should not put physicians at increased risk of liability, according to several experts.

In fact, physicians may face a lawsuit if they fail to offer it when indicated, suggested Steve Caritis, M.D.

“You can envision a woman who has had two previous preterm births and her physician doesn't raise this option. If she has another preterm birth there could be liability for not informing her that the therapy exists,” he said in an interview.

Dr. Caritis, professor and chief of maternal-fetal medicine at the University of Pittsburgh, was one of the investigators in the key study that led to the endorsement of progesterone therapy by the American College of Obstetricians and Gynecologists as a means of preventing preterm birth (ACOG Committee Opinion #291 [Obstet. Gynecol. 2003;102:1115–6]).

The randomized, placebo-controlled trial, conducted for the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, found that weekly intramuscular injections of 250 mg of 17 α-hydroxyprogesterone caproate (17-OHPC) decreased the risk of preterm birth by 34% in women with at least one spontaneous preterm birth (N. Engl. J. Med. 2003;348:2379–85).

ACOG's endorsement of the therapy stresses the importance of restricting it to this very select group of high-risk patients. The opinion notes that the drug “has been studied only as a prophylactic measure in asymptomatic women, not as a tocolytic agent,” and that further studies are needed to evaluate its use in women with multiple gestations, short cervical length, or positive test results for cervicovaginal fetal fibronectin. It also says that both the optimal route of drug delivery and its long-term safety remain unknown.

Given such issues, it is reasonable for physicians to have concerns about liability, but this should not deter them from prescribing the therapy where appropriate, said Larry Veltman, M.D., chair of ACOG's Committee on Professional Liability and chair of obstetrics and gynecology at Providence St. Vincent Medical Center in Portland, Ore.

“It is good medicine to have concerns about risks to the baby—this is a relatively new development and the risks and benefits still need to be thoroughly investigated. But to date, there have been no specific fetal or maternal risks identified,” he told this newspaper. The main point of the committee opinion was not to caution physicians about risks, but rather to inform them about the treatment, explained Laura Riley, M.D., who, as past chair of ACOG's Committee on Obstetric Practice, was involved in preparing the opinion on progesterone therapy.

“It brought this treatment to the attention of people who don't necessarily read the [New England Journal of Medicine], so that people would know this is one option—the only preventive option for preterm birth,” said Dr. Riley, medical director of labor and delivery at Massachusetts General Hospital in Boston.

Physicians at Northwest Perinatal Center, a subdivision of Women's Healthcare Associates in Portland, Ore., have been prescribing progesterone therapy for more than 2 years and until now have asked patients to sign a consent form stating that the treatment is not considered standard of care and that it does not ensure a term delivery, said Thomas Lee, M.D., a perinatologist who works at the center. “We are now questioning whether this is still necessary. The more experience we have with this therapy, the less concerned we are with liability issues,” he said, adding that more than 80% of the 20 patients they have treated with it have delivered after 35 weeks.

At the University of Illinois at Chicago, Sarah J. Kilpatrick, M.D., said she feels very comfortable about offering the treatment without any specific informed consent. “Personally, I don't think there's a risk of liability,” said the professor and head of obstetrics at the university.

“When you review the literature on risk of progesterone to the fetus you really can't come up with anything, but because there are no long-term data it is important to limit its use to only those women who can benefit from it. To me, the risk with progesterone is that people are going to use it inappropriately and therefore expose women to whom it may be not helpful,” Dr. Kilpatrick said.

Dr. Caritis agreed that long-term safety issues are probably not high on the list of concerns for most physicians prescribing this therapy, but quality control and standardization issues may be. Currently, a commercial preparation of 17-OHPC is not available, and the drug can be obtained only through compounding pharmacies.

“Compounding pharmacies do not have anybody regulating them, and what regulations they do have are kind of loose. Therefore, I think there's a concern from physicians about the quality of the compound that comes from these pharmacies. You don't know how they're making the product and whether they're doing the proper testing,” said Dr. Caritis.

He said a good compounding pharmacy should provide quality control information outlining its protocol for pyrogen, bacteriologic, and virologic testing, among other things.

The Maternal-Fetal Medicine Units Network is trying to interest a pharmaceutical company in marketing a commercial progesterone formulation for the prevention of preterm birth, said Dr. Caritis. However, there are other barriers that will have to be addressed, according to Dr. Kilpatrick. Less than half of the 30 patients who have been offered this treatment at her center have accepted it, she said. Cost is one of the issues. Although it is an inexpensive therapy (between $60 and $120 for a 10-week supply), Medicaid and most insurance companies will not pay for it, she said.

With proper informed consent, the prescription of progesterone to prevent preterm birth in appropriate patients should not put physicians at increased risk of liability, according to several experts.

In fact, physicians may face a lawsuit if they fail to offer it when indicated, suggested Steve Caritis, M.D.

“You can envision a woman who has had two previous preterm births and her physician doesn't raise this option. If she has another preterm birth there could be liability for not informing her that the therapy exists,” he said in an interview.

Dr. Caritis, professor and chief of maternal-fetal medicine at the University of Pittsburgh, was one of the investigators in the key study that led to the endorsement of progesterone therapy by the American College of Obstetricians and Gynecologists as a means of preventing preterm birth (ACOG Committee Opinion #291 [Obstet. Gynecol. 2003;102:1115–6]).

The randomized, placebo-controlled trial, conducted for the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, found that weekly intramuscular injections of 250 mg of 17 α-hydroxyprogesterone caproate (17-OHPC) decreased the risk of preterm birth by 34% in women with at least one spontaneous preterm birth (N. Engl. J. Med. 2003;348:2379–85).

ACOG's endorsement of the therapy stresses the importance of restricting it to this very select group of high-risk patients. The opinion notes that the drug “has been studied only as a prophylactic measure in asymptomatic women, not as a tocolytic agent,” and that further studies are needed to evaluate its use in women with multiple gestations, short cervical length, or positive test results for cervicovaginal fetal fibronectin. It also says that both the optimal route of drug delivery and its long-term safety remain unknown.

Given such issues, it is reasonable for physicians to have concerns about liability, but this should not deter them from prescribing the therapy where appropriate, said Larry Veltman, M.D., chair of ACOG's Committee on Professional Liability and chair of obstetrics and gynecology at Providence St. Vincent Medical Center in Portland, Ore.

“It is good medicine to have concerns about risks to the baby—this is a relatively new development and the risks and benefits still need to be thoroughly investigated. But to date, there have been no specific fetal or maternal risks identified,” he told this newspaper. The main point of the committee opinion was not to caution physicians about risks, but rather to inform them about the treatment, explained Laura Riley, M.D., who, as past chair of ACOG's Committee on Obstetric Practice, was involved in preparing the opinion on progesterone therapy.

“It brought this treatment to the attention of people who don't necessarily read the [New England Journal of Medicine], so that people would know this is one option—the only preventive option for preterm birth,” said Dr. Riley, medical director of labor and delivery at Massachusetts General Hospital in Boston.

Physicians at Northwest Perinatal Center, a subdivision of Women's Healthcare Associates in Portland, Ore., have been prescribing progesterone therapy for more than 2 years and until now have asked patients to sign a consent form stating that the treatment is not considered standard of care and that it does not ensure a term delivery, said Thomas Lee, M.D., a perinatologist who works at the center. “We are now questioning whether this is still necessary. The more experience we have with this therapy, the less concerned we are with liability issues,” he said, adding that more than 80% of the 20 patients they have treated with it have delivered after 35 weeks.

At the University of Illinois at Chicago, Sarah J. Kilpatrick, M.D., said she feels very comfortable about offering the treatment without any specific informed consent. “Personally, I don't think there's a risk of liability,” said the professor and head of obstetrics at the university.

“When you review the literature on risk of progesterone to the fetus you really can't come up with anything, but because there are no long-term data it is important to limit its use to only those women who can benefit from it. To me, the risk with progesterone is that people are going to use it inappropriately and therefore expose women to whom it may be not helpful,” Dr. Kilpatrick said.

Dr. Caritis agreed that long-term safety issues are probably not high on the list of concerns for most physicians prescribing this therapy, but quality control and standardization issues may be. Currently, a commercial preparation of 17-OHPC is not available, and the drug can be obtained only through compounding pharmacies.

“Compounding pharmacies do not have anybody regulating them, and what regulations they do have are kind of loose. Therefore, I think there's a concern from physicians about the quality of the compound that comes from these pharmacies. You don't know how they're making the product and whether they're doing the proper testing,” said Dr. Caritis.

He said a good compounding pharmacy should provide quality control information outlining its protocol for pyrogen, bacteriologic, and virologic testing, among other things.

The Maternal-Fetal Medicine Units Network is trying to interest a pharmaceutical company in marketing a commercial progesterone formulation for the prevention of preterm birth, said Dr. Caritis. However, there are other barriers that will have to be addressed, according to Dr. Kilpatrick. Less than half of the 30 patients who have been offered this treatment at her center have accepted it, she said. Cost is one of the issues. Although it is an inexpensive therapy (between $60 and $120 for a 10-week supply), Medicaid and most insurance companies will not pay for it, she said.

With proper informed consent, the prescription of progesterone to prevent preterm birth in appropriate patients should not put physicians at increased risk of liability, according to several experts.

In fact, physicians may face a lawsuit if they fail to offer it when indicated, suggested Steve Caritis, M.D.

“You can envision a woman who has had two previous preterm births and her physician doesn't raise this option. If she has another preterm birth there could be liability for not informing her that the therapy exists,” he said in an interview.

Dr. Caritis, professor and chief of maternal-fetal medicine at the University of Pittsburgh, was one of the investigators in the key study that led to the endorsement of progesterone therapy by the American College of Obstetricians and Gynecologists as a means of preventing preterm birth (ACOG Committee Opinion #291 [Obstet. Gynecol. 2003;102:1115–6]).

The randomized, placebo-controlled trial, conducted for the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, found that weekly intramuscular injections of 250 mg of 17 α-hydroxyprogesterone caproate (17-OHPC) decreased the risk of preterm birth by 34% in women with at least one spontaneous preterm birth (N. Engl. J. Med. 2003;348:2379–85).

ACOG's endorsement of the therapy stresses the importance of restricting it to this very select group of high-risk patients. The opinion notes that the drug “has been studied only as a prophylactic measure in asymptomatic women, not as a tocolytic agent,” and that further studies are needed to evaluate its use in women with multiple gestations, short cervical length, or positive test results for cervicovaginal fetal fibronectin. It also says that both the optimal route of drug delivery and its long-term safety remain unknown.

Given such issues, it is reasonable for physicians to have concerns about liability, but this should not deter them from prescribing the therapy where appropriate, said Larry Veltman, M.D., chair of ACOG's Committee on Professional Liability and chair of obstetrics and gynecology at Providence St. Vincent Medical Center in Portland, Ore.

“It is good medicine to have concerns about risks to the baby—this is a relatively new development and the risks and benefits still need to be thoroughly investigated. But to date, there have been no specific fetal or maternal risks identified,” he told this newspaper. The main point of the committee opinion was not to caution physicians about risks, but rather to inform them about the treatment, explained Laura Riley, M.D., who, as past chair of ACOG's Committee on Obstetric Practice, was involved in preparing the opinion on progesterone therapy.

“It brought this treatment to the attention of people who don't necessarily read the [New England Journal of Medicine], so that people would know this is one option—the only preventive option for preterm birth,” said Dr. Riley, medical director of labor and delivery at Massachusetts General Hospital in Boston.

Physicians at Northwest Perinatal Center, a subdivision of Women's Healthcare Associates in Portland, Ore., have been prescribing progesterone therapy for more than 2 years and until now have asked patients to sign a consent form stating that the treatment is not considered standard of care and that it does not ensure a term delivery, said Thomas Lee, M.D., a perinatologist who works at the center. “We are now questioning whether this is still necessary. The more experience we have with this therapy, the less concerned we are with liability issues,” he said, adding that more than 80% of the 20 patients they have treated with it have delivered after 35 weeks.

At the University of Illinois at Chicago, Sarah J. Kilpatrick, M.D., said she feels very comfortable about offering the treatment without any specific informed consent. “Personally, I don't think there's a risk of liability,” said the professor and head of obstetrics at the university.

“When you review the literature on risk of progesterone to the fetus you really can't come up with anything, but because there are no long-term data it is important to limit its use to only those women who can benefit from it. To me, the risk with progesterone is that people are going to use it inappropriately and therefore expose women to whom it may be not helpful,” Dr. Kilpatrick said.

Dr. Caritis agreed that long-term safety issues are probably not high on the list of concerns for most physicians prescribing this therapy, but quality control and standardization issues may be. Currently, a commercial preparation of 17-OHPC is not available, and the drug can be obtained only through compounding pharmacies.

“Compounding pharmacies do not have anybody regulating them, and what regulations they do have are kind of loose. Therefore, I think there's a concern from physicians about the quality of the compound that comes from these pharmacies. You don't know how they're making the product and whether they're doing the proper testing,” said Dr. Caritis.

He said a good compounding pharmacy should provide quality control information outlining its protocol for pyrogen, bacteriologic, and virologic testing, among other things.

The Maternal-Fetal Medicine Units Network is trying to interest a pharmaceutical company in marketing a commercial progesterone formulation for the prevention of preterm birth, said Dr. Caritis. However, there are other barriers that will have to be addressed, according to Dr. Kilpatrick. Less than half of the 30 patients who have been offered this treatment at her center have accepted it, she said. Cost is one of the issues. Although it is an inexpensive therapy (between $60 and $120 for a 10-week supply), Medicaid and most insurance companies will not pay for it, she said.

MONTREAL — Although the content of new resuscitation guidelines will not be released until December, the elimination of interruptions to chest compression during CPR is likely to be one of the major issues that is addressed.

The International Liaison Committee on Resuscitation (ILCOR) plans to publish an international consensus on the science for CPR and emergency cardiovascular care (ECC) in November, on which its member countries will base their resuscitation guidelines, said Marc Gay, who serves on the resuscitation policy advisory committee for the Heart and Stroke Foundation of Canada.

Although he would not hint at how the new guidelines will differ from current ones, he did suggest that CPR priorities need to change.

“There are certain things we need to do better,” he said in an interview at the International Interdisciplinary Conference on Emergencies.

“There have been recent studies showing that both in-hospital and out-of-hospital resuscitation attempts by paramedics are not good because there are too many distractions and interruptions.”

The last guideline update, in 2000, eliminated the recommendation of pulse checks for laypeople performing CPR in an attempt to improve efficiency, and cut down on their division of time, he said.

“Certainly, common sense says that even for health care professionals, there is a similar time limit,” he said.

Because 90% of all cardiac arrests are of cardiac etiology only, there is growing support for the idea that chest compression should take precedence over almost everything else in CPR, Mr. Gay said.

To that end, the fire department in Tucson, Ariz., working with the University of Arizona's Sarver Heart Center, recently abandoned current resuscitation guidelines in favor of a new CPR protocol that de-emphasizes many of the interruptions (rhythm analysis, defibrillation, tracheal intubation, and placement of intravenous catheters) and focuses on chest compressions (Resuscitation 2005;64:261–8).

Using data from their own controlled animal experiments, published clinical studies, and data from the 17-year-old fire department database, the researchers identified four main issues contributing to stagnant out-of-hospital cardiac arrest survival rates: lack of bystander CPR efforts; the complexity of CPR education for lay rescuers; an emphasis on defibrillation first, regardless of the duration of ventricular fibrillation; and frequent interruptions of chest compressions resulting in a marked compromise in circulatory support during resuscitation efforts.

An evaluation of the outcome of their protocol changes has not yet been done, but there is no doubt of the authors' political intent.

“A formalized, evidence-based process has been adopted by the International Liaison Committee on Resuscitation in formulating [its] guidelines,” the investigators wrote. “Currently, randomized clinical trials are considered optimal evidence, and very few major changes in the Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care are made without such. An alternative approach is to allow externally controlled clinical trials more weight in Guideline formulation and resuscitation protocol adoption.”

MONTREAL — Although the content of new resuscitation guidelines will not be released until December, the elimination of interruptions to chest compression during CPR is likely to be one of the major issues that is addressed.

The International Liaison Committee on Resuscitation (ILCOR) plans to publish an international consensus on the science for CPR and emergency cardiovascular care (ECC) in November, on which its member countries will base their resuscitation guidelines, said Marc Gay, who serves on the resuscitation policy advisory committee for the Heart and Stroke Foundation of Canada.

Although he would not hint at how the new guidelines will differ from current ones, he did suggest that CPR priorities need to change.

“There are certain things we need to do better,” he said in an interview at the International Interdisciplinary Conference on Emergencies.

“There have been recent studies showing that both in-hospital and out-of-hospital resuscitation attempts by paramedics are not good because there are too many distractions and interruptions.”

The last guideline update, in 2000, eliminated the recommendation of pulse checks for laypeople performing CPR in an attempt to improve efficiency, and cut down on their division of time, he said.

“Certainly, common sense says that even for health care professionals, there is a similar time limit,” he said.

Because 90% of all cardiac arrests are of cardiac etiology only, there is growing support for the idea that chest compression should take precedence over almost everything else in CPR, Mr. Gay said.

To that end, the fire department in Tucson, Ariz., working with the University of Arizona's Sarver Heart Center, recently abandoned current resuscitation guidelines in favor of a new CPR protocol that de-emphasizes many of the interruptions (rhythm analysis, defibrillation, tracheal intubation, and placement of intravenous catheters) and focuses on chest compressions (Resuscitation 2005;64:261–8).

Using data from their own controlled animal experiments, published clinical studies, and data from the 17-year-old fire department database, the researchers identified four main issues contributing to stagnant out-of-hospital cardiac arrest survival rates: lack of bystander CPR efforts; the complexity of CPR education for lay rescuers; an emphasis on defibrillation first, regardless of the duration of ventricular fibrillation; and frequent interruptions of chest compressions resulting in a marked compromise in circulatory support during resuscitation efforts.

An evaluation of the outcome of their protocol changes has not yet been done, but there is no doubt of the authors' political intent.

“A formalized, evidence-based process has been adopted by the International Liaison Committee on Resuscitation in formulating [its] guidelines,” the investigators wrote. “Currently, randomized clinical trials are considered optimal evidence, and very few major changes in the Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care are made without such. An alternative approach is to allow externally controlled clinical trials more weight in Guideline formulation and resuscitation protocol adoption.”

MONTREAL — Although the content of new resuscitation guidelines will not be released until December, the elimination of interruptions to chest compression during CPR is likely to be one of the major issues that is addressed.

The International Liaison Committee on Resuscitation (ILCOR) plans to publish an international consensus on the science for CPR and emergency cardiovascular care (ECC) in November, on which its member countries will base their resuscitation guidelines, said Marc Gay, who serves on the resuscitation policy advisory committee for the Heart and Stroke Foundation of Canada.

Although he would not hint at how the new guidelines will differ from current ones, he did suggest that CPR priorities need to change.

“There are certain things we need to do better,” he said in an interview at the International Interdisciplinary Conference on Emergencies.

“There have been recent studies showing that both in-hospital and out-of-hospital resuscitation attempts by paramedics are not good because there are too many distractions and interruptions.”

The last guideline update, in 2000, eliminated the recommendation of pulse checks for laypeople performing CPR in an attempt to improve efficiency, and cut down on their division of time, he said.

“Certainly, common sense says that even for health care professionals, there is a similar time limit,” he said.

Because 90% of all cardiac arrests are of cardiac etiology only, there is growing support for the idea that chest compression should take precedence over almost everything else in CPR, Mr. Gay said.

To that end, the fire department in Tucson, Ariz., working with the University of Arizona's Sarver Heart Center, recently abandoned current resuscitation guidelines in favor of a new CPR protocol that de-emphasizes many of the interruptions (rhythm analysis, defibrillation, tracheal intubation, and placement of intravenous catheters) and focuses on chest compressions (Resuscitation 2005;64:261–8).

Using data from their own controlled animal experiments, published clinical studies, and data from the 17-year-old fire department database, the researchers identified four main issues contributing to stagnant out-of-hospital cardiac arrest survival rates: lack of bystander CPR efforts; the complexity of CPR education for lay rescuers; an emphasis on defibrillation first, regardless of the duration of ventricular fibrillation; and frequent interruptions of chest compressions resulting in a marked compromise in circulatory support during resuscitation efforts.

An evaluation of the outcome of their protocol changes has not yet been done, but there is no doubt of the authors' political intent.

“A formalized, evidence-based process has been adopted by the International Liaison Committee on Resuscitation in formulating [its] guidelines,” the investigators wrote. “Currently, randomized clinical trials are considered optimal evidence, and very few major changes in the Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care are made without such. An alternative approach is to allow externally controlled clinical trials more weight in Guideline formulation and resuscitation protocol adoption.”

MONTREAL – Psychotherapy for eating disorders can be delivered effectively by e-mail and can reach a segment of the population that might otherwise decline treatment, Paul Robinson, M.D., said at an international conference sponsored by the Academy for Eating Disorders.

He recruited 97 participants with eating disorders from a university e-mail list for his study. The diagnoses of bulimia nervosa, binge-eating disorder, and eating disorders not otherwise specified (EDNOS) all fulfilled DSM-IV criteria and were made using online questionnaires and assessments.

Roughly 80% of the cohort had received no previous treatment for their eating disorder, said Dr. Robinson, a psychiatrist with the eating disorders service of Royal Free Hospital, London.

“They were a population of people who don't approach mental health care or any sort of health care, and they said they wouldn't have done so if it hadn't been for this program,” Dr. Robinson said in an interview.

Study participants were randomized to e-mail bulimia therapy (EBT), to self-directed writing (SDW), or to a treatment waiting list, which was the control, he said.

The EBT group (36) received 12 weeks of e-mail therapy from professionals who were experienced in the outpatient management of eating disorders. Participants were asked to write twice weekly in a food, behavior, and emotions diary, to which the therapists responded.

“We looked at the diary and annotated it with our own comments,” said Dr. Robinson. “For example, if a patient wrote that she had eaten nothing for breakfast or lunch and then binged in the evening, we might have responded by saying that eating nothing all day might be triggering the binge at night,” he said.

Participants in the SDW group (34) were asked to write about their eating disorder and e-mail their comments to Dr. Robinson twice a week, although he acknowledged the e-mails he sent did not offer specific counseling to this group.

“They knew I was reading [their comments], and they knew that if I thought they were in danger I would act, and I think that was important to them,” he said.

Participants in the control group (27) waited 12 weeks and were then randomized to either EBT or SDW.

At the 12-week assessment, the e-mail therapy and SDW groups were combined into one “E-Therapy” group and compared with the control group.

The results showed that, while none of the control participants lost their eating disorder diagnosis, 18.6% of the E-Therapy group did.

Assessments using the Bulimic Investigatory Test, Edinburgh (BITE), severity and symptom scores showed a mean reduction in BITE severity score of 1.2 in the E-Therapy group, compared with a reduction of 0.2 in the control group. Similarly, the mean reduction in the BITE symptom score was significantly greater in the E-Therapy group (2.1 versus 0.3).

When asked about their desired body mass index (BMI), participants who had completed the e-mail therapy indicated that they were more willing to accept the idea of a higher BMI than were those participants in the control group.

There was a significant correlation between the number of words a participant wrote and the degree of symptom improvements in the e-mail bulimia therapy group only, Dr. Robinson said.

“It is hard to explain the response in the self-directed writing group, although there is quite a lot in the literature about the therapeutic efficacy of writing, and how it can lower depression scores,” he noted.

Although the study found no difference in outcome between EBT and SDW, there was a trend in favor of EBT. “In a bigger study, I would expect and hope that therapy patients would do better,” he said.

E-mail therapy was well accepted by the participants, with 84% saying that they would be willing to engage in further therapy either online or face to face. There also was a feeling among therapists that this form of therapy took about half the time of traditional therapy, although it was not measured, Dr. Robinson said.

MONTREAL – Psychotherapy for eating disorders can be delivered effectively by e-mail and can reach a segment of the population that might otherwise decline treatment, Paul Robinson, M.D., said at an international conference sponsored by the Academy for Eating Disorders.

He recruited 97 participants with eating disorders from a university e-mail list for his study. The diagnoses of bulimia nervosa, binge-eating disorder, and eating disorders not otherwise specified (EDNOS) all fulfilled DSM-IV criteria and were made using online questionnaires and assessments.

Roughly 80% of the cohort had received no previous treatment for their eating disorder, said Dr. Robinson, a psychiatrist with the eating disorders service of Royal Free Hospital, London.

“They were a population of people who don't approach mental health care or any sort of health care, and they said they wouldn't have done so if it hadn't been for this program,” Dr. Robinson said in an interview.

Study participants were randomized to e-mail bulimia therapy (EBT), to self-directed writing (SDW), or to a treatment waiting list, which was the control, he said.

The EBT group (36) received 12 weeks of e-mail therapy from professionals who were experienced in the outpatient management of eating disorders. Participants were asked to write twice weekly in a food, behavior, and emotions diary, to which the therapists responded.

“We looked at the diary and annotated it with our own comments,” said Dr. Robinson. “For example, if a patient wrote that she had eaten nothing for breakfast or lunch and then binged in the evening, we might have responded by saying that eating nothing all day might be triggering the binge at night,” he said.

Participants in the SDW group (34) were asked to write about their eating disorder and e-mail their comments to Dr. Robinson twice a week, although he acknowledged the e-mails he sent did not offer specific counseling to this group.

“They knew I was reading [their comments], and they knew that if I thought they were in danger I would act, and I think that was important to them,” he said.

Participants in the control group (27) waited 12 weeks and were then randomized to either EBT or SDW.

At the 12-week assessment, the e-mail therapy and SDW groups were combined into one “E-Therapy” group and compared with the control group.

The results showed that, while none of the control participants lost their eating disorder diagnosis, 18.6% of the E-Therapy group did.

Assessments using the Bulimic Investigatory Test, Edinburgh (BITE), severity and symptom scores showed a mean reduction in BITE severity score of 1.2 in the E-Therapy group, compared with a reduction of 0.2 in the control group. Similarly, the mean reduction in the BITE symptom score was significantly greater in the E-Therapy group (2.1 versus 0.3).

When asked about their desired body mass index (BMI), participants who had completed the e-mail therapy indicated that they were more willing to accept the idea of a higher BMI than were those participants in the control group.

There was a significant correlation between the number of words a participant wrote and the degree of symptom improvements in the e-mail bulimia therapy group only, Dr. Robinson said.

“It is hard to explain the response in the self-directed writing group, although there is quite a lot in the literature about the therapeutic efficacy of writing, and how it can lower depression scores,” he noted.

Although the study found no difference in outcome between EBT and SDW, there was a trend in favor of EBT. “In a bigger study, I would expect and hope that therapy patients would do better,” he said.

E-mail therapy was well accepted by the participants, with 84% saying that they would be willing to engage in further therapy either online or face to face. There also was a feeling among therapists that this form of therapy took about half the time of traditional therapy, although it was not measured, Dr. Robinson said.

MONTREAL – Psychotherapy for eating disorders can be delivered effectively by e-mail and can reach a segment of the population that might otherwise decline treatment, Paul Robinson, M.D., said at an international conference sponsored by the Academy for Eating Disorders.

He recruited 97 participants with eating disorders from a university e-mail list for his study. The diagnoses of bulimia nervosa, binge-eating disorder, and eating disorders not otherwise specified (EDNOS) all fulfilled DSM-IV criteria and were made using online questionnaires and assessments.

Roughly 80% of the cohort had received no previous treatment for their eating disorder, said Dr. Robinson, a psychiatrist with the eating disorders service of Royal Free Hospital, London.

“They were a population of people who don't approach mental health care or any sort of health care, and they said they wouldn't have done so if it hadn't been for this program,” Dr. Robinson said in an interview.

Study participants were randomized to e-mail bulimia therapy (EBT), to self-directed writing (SDW), or to a treatment waiting list, which was the control, he said.

The EBT group (36) received 12 weeks of e-mail therapy from professionals who were experienced in the outpatient management of eating disorders. Participants were asked to write twice weekly in a food, behavior, and emotions diary, to which the therapists responded.

“We looked at the diary and annotated it with our own comments,” said Dr. Robinson. “For example, if a patient wrote that she had eaten nothing for breakfast or lunch and then binged in the evening, we might have responded by saying that eating nothing all day might be triggering the binge at night,” he said.

Participants in the SDW group (34) were asked to write about their eating disorder and e-mail their comments to Dr. Robinson twice a week, although he acknowledged the e-mails he sent did not offer specific counseling to this group.

“They knew I was reading [their comments], and they knew that if I thought they were in danger I would act, and I think that was important to them,” he said.

Participants in the control group (27) waited 12 weeks and were then randomized to either EBT or SDW.

At the 12-week assessment, the e-mail therapy and SDW groups were combined into one “E-Therapy” group and compared with the control group.

The results showed that, while none of the control participants lost their eating disorder diagnosis, 18.6% of the E-Therapy group did.

Assessments using the Bulimic Investigatory Test, Edinburgh (BITE), severity and symptom scores showed a mean reduction in BITE severity score of 1.2 in the E-Therapy group, compared with a reduction of 0.2 in the control group. Similarly, the mean reduction in the BITE symptom score was significantly greater in the E-Therapy group (2.1 versus 0.3).

When asked about their desired body mass index (BMI), participants who had completed the e-mail therapy indicated that they were more willing to accept the idea of a higher BMI than were those participants in the control group.

There was a significant correlation between the number of words a participant wrote and the degree of symptom improvements in the e-mail bulimia therapy group only, Dr. Robinson said.

“It is hard to explain the response in the self-directed writing group, although there is quite a lot in the literature about the therapeutic efficacy of writing, and how it can lower depression scores,” he noted.

Although the study found no difference in outcome between EBT and SDW, there was a trend in favor of EBT. “In a bigger study, I would expect and hope that therapy patients would do better,” he said.

E-mail therapy was well accepted by the participants, with 84% saying that they would be willing to engage in further therapy either online or face to face. There also was a feeling among therapists that this form of therapy took about half the time of traditional therapy, although it was not measured, Dr. Robinson said.

MONTREAL – Treatment for anorexia nervosa might one day use videotapes of family meals to personalize therapy for patients, according to a pilot study.

Family mealtimes play a central role in anorexia nervosa, not only because of their focus on eating, but also because of their focus on family interaction, said investigator Richard L. Levine, M.D., who presented his study as a poster at an international conference sponsored by the Academy for Eating Disorders.

“In terms of the etiology of eating disorders, family interactions matter,” said Dr. Levine, director of the eating disorders program at the Milton S. Hershey Medical Center, in Hershey, Pa.

“We recognize there is a biological predisposition to eating disorders in terms of genetics and the imbalance of neurotransmitters, and there are also certain cultural pressures from the food and fashion industries. But family interactions also exert influence on patients and their eating habits,” he said in an interview.

For example, quantitative research shows that interactions in families of anorexic patients are often characterized by parental overprotection, enmeshment, rigidity, and poor conflict resolution, he said. In addition, maternal anxiety and “high concern parenting” in early and middle childhood correlate with anorexia nervosa.

The investigators sought to determine whether qualitative findings could confirm some of those themes.

The study included three female patients, ranging in age from 17 to 19 years, who each videotaped five family meals and between three and five monologues, or “video diaries.”

The patients also completed three psychological measures, which included the Family Environment Scale, the Minnesota Multiphasic Personality Inventory-Adolescent, and the Eating Disorder Inventory-2.

The themes that emerged from the videos and the psychological assessments identified families that were paternally dominant and highly critical–consistent with the quantitative research, said Elizabeth Hoffman, Ph.D., another investigator and manager at the same eating disorders program. “Fathers dominated the conversation at the meals, there was a lot of criticism of others outside of the family, and there was a lot of sibling competition and focus on achievement,” Dr. Hoffman told this newspaper.

Family therapy has traditionally attempted to address many of those issues, but it is usually on family interactions that occur in an artificial environment, she explained.

“Videotapes illuminate family patterns that we don't usually see in the regular family therapy environment, which could help us target therapy more appropriately,” she said.

In contrast to the families of anorexic patients, families of patients with bulimia nervosa are in many ways the mirror opposite, Dr. Levine said.

Those families of bulimia patients tend to be less structured, with fewer guidelines and less parenting in general, he said. There is more chaos in the family and often more chaos in the patients,” he said.

A separate poster presented at the meeting confirmed this general trend.

In a survey of 124 college undergraduates, Daniel J. Munoz and his colleagues at the University at Albany, State University of New York, analyzed family mealtime frequency and family stability and how they related to the symptomatology of bulimia.

They found that greater frequency of family mealtimes and higher levels of family stability, as measured by the SAFE test (Stability of Activities in a Family Environment), predicted a decreased likelihood of bulimia as measured by the Eating Disorders Inventory-2 and the Bulimia Test-Revised.

“Examining the regularity of family activities–including mealtimes–may provide an additional pathway toward assessment, intervention, and prevention of bulimia,” they wrote.

MONTREAL – Treatment for anorexia nervosa might one day use videotapes of family meals to personalize therapy for patients, according to a pilot study.

Family mealtimes play a central role in anorexia nervosa, not only because of their focus on eating, but also because of their focus on family interaction, said investigator Richard L. Levine, M.D., who presented his study as a poster at an international conference sponsored by the Academy for Eating Disorders.

“In terms of the etiology of eating disorders, family interactions matter,” said Dr. Levine, director of the eating disorders program at the Milton S. Hershey Medical Center, in Hershey, Pa.

“We recognize there is a biological predisposition to eating disorders in terms of genetics and the imbalance of neurotransmitters, and there are also certain cultural pressures from the food and fashion industries. But family interactions also exert influence on patients and their eating habits,” he said in an interview.

For example, quantitative research shows that interactions in families of anorexic patients are often characterized by parental overprotection, enmeshment, rigidity, and poor conflict resolution, he said. In addition, maternal anxiety and “high concern parenting” in early and middle childhood correlate with anorexia nervosa.

The investigators sought to determine whether qualitative findings could confirm some of those themes.

The study included three female patients, ranging in age from 17 to 19 years, who each videotaped five family meals and between three and five monologues, or “video diaries.”

The patients also completed three psychological measures, which included the Family Environment Scale, the Minnesota Multiphasic Personality Inventory-Adolescent, and the Eating Disorder Inventory-2.

The themes that emerged from the videos and the psychological assessments identified families that were paternally dominant and highly critical–consistent with the quantitative research, said Elizabeth Hoffman, Ph.D., another investigator and manager at the same eating disorders program. “Fathers dominated the conversation at the meals, there was a lot of criticism of others outside of the family, and there was a lot of sibling competition and focus on achievement,” Dr. Hoffman told this newspaper.

Family therapy has traditionally attempted to address many of those issues, but it is usually on family interactions that occur in an artificial environment, she explained.

“Videotapes illuminate family patterns that we don't usually see in the regular family therapy environment, which could help us target therapy more appropriately,” she said.

In contrast to the families of anorexic patients, families of patients with bulimia nervosa are in many ways the mirror opposite, Dr. Levine said.

Those families of bulimia patients tend to be less structured, with fewer guidelines and less parenting in general, he said. There is more chaos in the family and often more chaos in the patients,” he said.

A separate poster presented at the meeting confirmed this general trend.

In a survey of 124 college undergraduates, Daniel J. Munoz and his colleagues at the University at Albany, State University of New York, analyzed family mealtime frequency and family stability and how they related to the symptomatology of bulimia.

They found that greater frequency of family mealtimes and higher levels of family stability, as measured by the SAFE test (Stability of Activities in a Family Environment), predicted a decreased likelihood of bulimia as measured by the Eating Disorders Inventory-2 and the Bulimia Test-Revised.

“Examining the regularity of family activities–including mealtimes–may provide an additional pathway toward assessment, intervention, and prevention of bulimia,” they wrote.

MONTREAL – Treatment for anorexia nervosa might one day use videotapes of family meals to personalize therapy for patients, according to a pilot study.

Family mealtimes play a central role in anorexia nervosa, not only because of their focus on eating, but also because of their focus on family interaction, said investigator Richard L. Levine, M.D., who presented his study as a poster at an international conference sponsored by the Academy for Eating Disorders.

“In terms of the etiology of eating disorders, family interactions matter,” said Dr. Levine, director of the eating disorders program at the Milton S. Hershey Medical Center, in Hershey, Pa.

“We recognize there is a biological predisposition to eating disorders in terms of genetics and the imbalance of neurotransmitters, and there are also certain cultural pressures from the food and fashion industries. But family interactions also exert influence on patients and their eating habits,” he said in an interview.

For example, quantitative research shows that interactions in families of anorexic patients are often characterized by parental overprotection, enmeshment, rigidity, and poor conflict resolution, he said. In addition, maternal anxiety and “high concern parenting” in early and middle childhood correlate with anorexia nervosa.

The investigators sought to determine whether qualitative findings could confirm some of those themes.

The study included three female patients, ranging in age from 17 to 19 years, who each videotaped five family meals and between three and five monologues, or “video diaries.”

The patients also completed three psychological measures, which included the Family Environment Scale, the Minnesota Multiphasic Personality Inventory-Adolescent, and the Eating Disorder Inventory-2.

The themes that emerged from the videos and the psychological assessments identified families that were paternally dominant and highly critical–consistent with the quantitative research, said Elizabeth Hoffman, Ph.D., another investigator and manager at the same eating disorders program. “Fathers dominated the conversation at the meals, there was a lot of criticism of others outside of the family, and there was a lot of sibling competition and focus on achievement,” Dr. Hoffman told this newspaper.

Family therapy has traditionally attempted to address many of those issues, but it is usually on family interactions that occur in an artificial environment, she explained.

“Videotapes illuminate family patterns that we don't usually see in the regular family therapy environment, which could help us target therapy more appropriately,” she said.

In contrast to the families of anorexic patients, families of patients with bulimia nervosa are in many ways the mirror opposite, Dr. Levine said.

Those families of bulimia patients tend to be less structured, with fewer guidelines and less parenting in general, he said. There is more chaos in the family and often more chaos in the patients,” he said.

A separate poster presented at the meeting confirmed this general trend.

In a survey of 124 college undergraduates, Daniel J. Munoz and his colleagues at the University at Albany, State University of New York, analyzed family mealtime frequency and family stability and how they related to the symptomatology of bulimia.

They found that greater frequency of family mealtimes and higher levels of family stability, as measured by the SAFE test (Stability of Activities in a Family Environment), predicted a decreased likelihood of bulimia as measured by the Eating Disorders Inventory-2 and the Bulimia Test-Revised.

“Examining the regularity of family activities–including mealtimes–may provide an additional pathway toward assessment, intervention, and prevention of bulimia,” they wrote.

MONTREAL — The most common emergency department treatments for cardiogenic pulmonary edema actually make the condition worse and should be abandoned in favor of aggressive, high-dose nitroglycerin combined with angiotensin-converting enzyme inhibitors, Amal Mattu, M.D., said at the International Interdisciplinary Conference on Emergencies.

Most emergency physicians combine low doses of nitroglycerin (NTG) with either morphine or a diuretic, or a combination of both—to the detriment of the patient, according to Dr. Mattu of the University of Maryland, Baltimore.

“For most physicians, nitroglycerin is first-line therapy, but it is still very underdosed. Most physicians are still not comfortable reaching doses like 50 mcg to 100 mcg to 200 mcg per minute—they are using very low doses, which don't really help that much,” he said in an interview with this newspaper.

Dr. Mattu recommends aggressive use of NTG sublingually as first-line therapy for rapid and effective treatment initiation, followed by topical NTG in those with moderate symptoms and intravenous NTG in those with the severe symptoms.

Caution should be exercised in hypotensive patients as well as those patients with acute mitral regurgitation, aortic stenosis, pulmonary hypertension, and those taking sildenafil, he said.

The goals in treating cardiogenic pulmonary edema (CPE) patients should be to decrease preload and afterload—both of which can be done with aggressive NTG therapy, Dr. Mattu said.

Although morphine is a common addition to the NTG regimen for preload reduction, there is very little evidence that it is effective in this regard, he said.

In fact, there is significant evidence that it can cause respiratory and myocardial depression at high doses, Dr. Mattu said, and its histamine-related side effects such as rash, urticaria, nausea, and vomiting can actually increase catecholamine release, which worsens the problem.

The basis for morphine's reputation for decreasing preload largely comes from studies in the 1970s in which morphine produced venodilation in the hands and forearms of pulmonary edema patients (Circulation 1976;54:335–7), but a handful of more recent studies actually show deterioration in patients receiving morphine, he said.

Furthermore, an abstract presented at this year's Society for Academic Emergency Medicine meeting demonstrated an almost fivefold increase in mortality among acute decompensated heart failure patients receiving morphine, compared with those who were not.

“Once this study is published, it may almost be malpractice to administer morphine to these patients,” Dr. Mattu said.

The other common addition to NTG therapy is a diuretic such as furosemide to aid in preload reduction and act as a vasodilator.

But because many CPE patients have significantly impaired renal blood flow, this therapy takes between 30 minutes and 2 hours to reach the kidneys and initiate diuretic action, said Dr. Mattu.

It is important to remember that up to 50% of pulmonary edema patients may have general body euvolemia and are not actually fluid overloaded; they just have the wrong distribution of fluid in their lungs. “Diuretics drain the body, but not the lungs, so they will not necessarily produce the desired effect,” he said.

Again, although studies showing hand and forearm venodilation with furosemide have formed the basis for this treatment approach (Circulation 1997;96:1847–52), many more studies demonstrate initial adverse hemodynamic effects, with only a delayed reduction in preload, Dr. Mattu said.

“This should be a third-line medication,” he added.

For afterload and preload reduction, Dr. Mattu recommended angiotensin converting enzyme (ACE) inhibitors (enalapril or captopril), either intravenously or sublingually, as second-line therapy after NTG. This therapy produces an abrupt increase in diuresis even prior to the use of a diuretic, by improving renal blood flow, and significant hemodynamic and subjective improvements in as little as 6–12 minutes, he said.

“This is something I hope more people will catch on to. Almost everybody who I know who has tried this is a big fan of it,” he said. “They are seeing a lot of patients who look like they are going to need intubation who will often turn around within 15 minutes and not need intubation, and often not even need to go to the intensive care unit.”

The combination of ACE inhibitors with NTG therapy exceeds the benefit of either drug alone; however, ACE inhibitors are also an acceptable single agent for patients who cannot tolerate NTG therapy, he said.

The use of the recombinant natriuretic peptide nesiritide has come under fire recently, Dr. Mattu said, after publication of two metaanalyses associating it with increases in mortality and worsening of renal function in acute decompensated heart failure patients (Circulation 2005;111:1487–91; JAMA 2005;293:1900–5).

“This therapy is unproven as an additional therapy in patients who are already receiving optimal treatment,” he said.

MONTREAL — The most common emergency department treatments for cardiogenic pulmonary edema actually make the condition worse and should be abandoned in favor of aggressive, high-dose nitroglycerin combined with angiotensin-converting enzyme inhibitors, Amal Mattu, M.D., said at the International Interdisciplinary Conference on Emergencies.

Most emergency physicians combine low doses of nitroglycerin (NTG) with either morphine or a diuretic, or a combination of both—to the detriment of the patient, according to Dr. Mattu of the University of Maryland, Baltimore.

“For most physicians, nitroglycerin is first-line therapy, but it is still very underdosed. Most physicians are still not comfortable reaching doses like 50 mcg to 100 mcg to 200 mcg per minute—they are using very low doses, which don't really help that much,” he said in an interview with this newspaper.

Dr. Mattu recommends aggressive use of NTG sublingually as first-line therapy for rapid and effective treatment initiation, followed by topical NTG in those with moderate symptoms and intravenous NTG in those with the severe symptoms.

Caution should be exercised in hypotensive patients as well as those patients with acute mitral regurgitation, aortic stenosis, pulmonary hypertension, and those taking sildenafil, he said.

The goals in treating cardiogenic pulmonary edema (CPE) patients should be to decrease preload and afterload—both of which can be done with aggressive NTG therapy, Dr. Mattu said.

Although morphine is a common addition to the NTG regimen for preload reduction, there is very little evidence that it is effective in this regard, he said.

In fact, there is significant evidence that it can cause respiratory and myocardial depression at high doses, Dr. Mattu said, and its histamine-related side effects such as rash, urticaria, nausea, and vomiting can actually increase catecholamine release, which worsens the problem.

The basis for morphine's reputation for decreasing preload largely comes from studies in the 1970s in which morphine produced venodilation in the hands and forearms of pulmonary edema patients (Circulation 1976;54:335–7), but a handful of more recent studies actually show deterioration in patients receiving morphine, he said.

Furthermore, an abstract presented at this year's Society for Academic Emergency Medicine meeting demonstrated an almost fivefold increase in mortality among acute decompensated heart failure patients receiving morphine, compared with those who were not.

“Once this study is published, it may almost be malpractice to administer morphine to these patients,” Dr. Mattu said.

The other common addition to NTG therapy is a diuretic such as furosemide to aid in preload reduction and act as a vasodilator.

But because many CPE patients have significantly impaired renal blood flow, this therapy takes between 30 minutes and 2 hours to reach the kidneys and initiate diuretic action, said Dr. Mattu.

It is important to remember that up to 50% of pulmonary edema patients may have general body euvolemia and are not actually fluid overloaded; they just have the wrong distribution of fluid in their lungs. “Diuretics drain the body, but not the lungs, so they will not necessarily produce the desired effect,” he said.

Again, although studies showing hand and forearm venodilation with furosemide have formed the basis for this treatment approach (Circulation 1997;96:1847–52), many more studies demonstrate initial adverse hemodynamic effects, with only a delayed reduction in preload, Dr. Mattu said.

“This should be a third-line medication,” he added.

For afterload and preload reduction, Dr. Mattu recommended angiotensin converting enzyme (ACE) inhibitors (enalapril or captopril), either intravenously or sublingually, as second-line therapy after NTG. This therapy produces an abrupt increase in diuresis even prior to the use of a diuretic, by improving renal blood flow, and significant hemodynamic and subjective improvements in as little as 6–12 minutes, he said.

“This is something I hope more people will catch on to. Almost everybody who I know who has tried this is a big fan of it,” he said. “They are seeing a lot of patients who look like they are going to need intubation who will often turn around within 15 minutes and not need intubation, and often not even need to go to the intensive care unit.”

The combination of ACE inhibitors with NTG therapy exceeds the benefit of either drug alone; however, ACE inhibitors are also an acceptable single agent for patients who cannot tolerate NTG therapy, he said.

The use of the recombinant natriuretic peptide nesiritide has come under fire recently, Dr. Mattu said, after publication of two metaanalyses associating it with increases in mortality and worsening of renal function in acute decompensated heart failure patients (Circulation 2005;111:1487–91; JAMA 2005;293:1900–5).

“This therapy is unproven as an additional therapy in patients who are already receiving optimal treatment,” he said.

MONTREAL — The most common emergency department treatments for cardiogenic pulmonary edema actually make the condition worse and should be abandoned in favor of aggressive, high-dose nitroglycerin combined with angiotensin-converting enzyme inhibitors, Amal Mattu, M.D., said at the International Interdisciplinary Conference on Emergencies.

Most emergency physicians combine low doses of nitroglycerin (NTG) with either morphine or a diuretic, or a combination of both—to the detriment of the patient, according to Dr. Mattu of the University of Maryland, Baltimore.

“For most physicians, nitroglycerin is first-line therapy, but it is still very underdosed. Most physicians are still not comfortable reaching doses like 50 mcg to 100 mcg to 200 mcg per minute—they are using very low doses, which don't really help that much,” he said in an interview with this newspaper.

Dr. Mattu recommends aggressive use of NTG sublingually as first-line therapy for rapid and effective treatment initiation, followed by topical NTG in those with moderate symptoms and intravenous NTG in those with the severe symptoms.

Caution should be exercised in hypotensive patients as well as those patients with acute mitral regurgitation, aortic stenosis, pulmonary hypertension, and those taking sildenafil, he said.

The goals in treating cardiogenic pulmonary edema (CPE) patients should be to decrease preload and afterload—both of which can be done with aggressive NTG therapy, Dr. Mattu said.

Although morphine is a common addition to the NTG regimen for preload reduction, there is very little evidence that it is effective in this regard, he said.

In fact, there is significant evidence that it can cause respiratory and myocardial depression at high doses, Dr. Mattu said, and its histamine-related side effects such as rash, urticaria, nausea, and vomiting can actually increase catecholamine release, which worsens the problem.

The basis for morphine's reputation for decreasing preload largely comes from studies in the 1970s in which morphine produced venodilation in the hands and forearms of pulmonary edema patients (Circulation 1976;54:335–7), but a handful of more recent studies actually show deterioration in patients receiving morphine, he said.

Furthermore, an abstract presented at this year's Society for Academic Emergency Medicine meeting demonstrated an almost fivefold increase in mortality among acute decompensated heart failure patients receiving morphine, compared with those who were not.

“Once this study is published, it may almost be malpractice to administer morphine to these patients,” Dr. Mattu said.

The other common addition to NTG therapy is a diuretic such as furosemide to aid in preload reduction and act as a vasodilator.

But because many CPE patients have significantly impaired renal blood flow, this therapy takes between 30 minutes and 2 hours to reach the kidneys and initiate diuretic action, said Dr. Mattu.

It is important to remember that up to 50% of pulmonary edema patients may have general body euvolemia and are not actually fluid overloaded; they just have the wrong distribution of fluid in their lungs. “Diuretics drain the body, but not the lungs, so they will not necessarily produce the desired effect,” he said.

Again, although studies showing hand and forearm venodilation with furosemide have formed the basis for this treatment approach (Circulation 1997;96:1847–52), many more studies demonstrate initial adverse hemodynamic effects, with only a delayed reduction in preload, Dr. Mattu said.

“This should be a third-line medication,” he added.

For afterload and preload reduction, Dr. Mattu recommended angiotensin converting enzyme (ACE) inhibitors (enalapril or captopril), either intravenously or sublingually, as second-line therapy after NTG. This therapy produces an abrupt increase in diuresis even prior to the use of a diuretic, by improving renal blood flow, and significant hemodynamic and subjective improvements in as little as 6–12 minutes, he said.

“This is something I hope more people will catch on to. Almost everybody who I know who has tried this is a big fan of it,” he said. “They are seeing a lot of patients who look like they are going to need intubation who will often turn around within 15 minutes and not need intubation, and often not even need to go to the intensive care unit.”

The combination of ACE inhibitors with NTG therapy exceeds the benefit of either drug alone; however, ACE inhibitors are also an acceptable single agent for patients who cannot tolerate NTG therapy, he said.

The use of the recombinant natriuretic peptide nesiritide has come under fire recently, Dr. Mattu said, after publication of two metaanalyses associating it with increases in mortality and worsening of renal function in acute decompensated heart failure patients (Circulation 2005;111:1487–91; JAMA 2005;293:1900–5).

“This therapy is unproven as an additional therapy in patients who are already receiving optimal treatment,” he said.

COPENHAGEN — Early embryo transfer on the first day after fertilization may remedy certain in vitro fertilization failures due to poor embryo quality, researchers reported in a poster presented at the annual meeting of the European Society of Human Reproduction and Embryology.

A subset of patients with good ovarian stimulation, egg quality, and fertilization have embryos that stop developing or exhibit extended fragmentation by their second day in culture, said Olia Anastasiou of the Laboratoire de VIF et de Biologie de la Reproduction at Hôpital Tenon in Paris.

“We have patients like this, most of whom have had three trials of [in vitro fertilization] with really bad quality embryos. It's been a real question mark what to do for them,” she said in an interview.

Prolonging embryo culture to the blastocyst stage (day 5) for such patients is a risk that usually results in no surviving embryos to transfer, she explained.

Her team's hypothesis was that certain maternal proteins, which are normally responsible for preimplantation embryo development, were deficient in these patients, making their embryos unable to survive the culture conditions in vitro.

For this group, they investigated the benefit of early embryo transfer at the pronuclear stage, just 1 day after fertilization.

A total of 27 patients were initially included in the study. The average age of the patients was 35 years; all had experienced at least two in vitro fertilization [IVF] failures due to “drastically impaired” embryonic development. None had achieved a pregnancy despite normal parental karyotypes and sperm DNA fragmentation rates.

The patients had their third and fourth IVF cycles performed with transfer and cryopreservation of pronuclear-stage embryos. Eight clinical pregnancies were obtained, representing a pregnancy rate of 29% and an implantation rate of 14%.

Data now have been collected for 50 patients—15 of whom have become pregnant, for a pregnancy rate of 27%.

“We were surprised ourselves since between all of these patients we had performed more than 180 cycles with absolutely no pregnancy,” she said.

No pregnancies have yet been reported from the cryopreserved embryos.

COPENHAGEN — Early embryo transfer on the first day after fertilization may remedy certain in vitro fertilization failures due to poor embryo quality, researchers reported in a poster presented at the annual meeting of the European Society of Human Reproduction and Embryology.

A subset of patients with good ovarian stimulation, egg quality, and fertilization have embryos that stop developing or exhibit extended fragmentation by their second day in culture, said Olia Anastasiou of the Laboratoire de VIF et de Biologie de la Reproduction at Hôpital Tenon in Paris.

“We have patients like this, most of whom have had three trials of [in vitro fertilization] with really bad quality embryos. It's been a real question mark what to do for them,” she said in an interview.

Prolonging embryo culture to the blastocyst stage (day 5) for such patients is a risk that usually results in no surviving embryos to transfer, she explained.

Her team's hypothesis was that certain maternal proteins, which are normally responsible for preimplantation embryo development, were deficient in these patients, making their embryos unable to survive the culture conditions in vitro.

For this group, they investigated the benefit of early embryo transfer at the pronuclear stage, just 1 day after fertilization.

A total of 27 patients were initially included in the study. The average age of the patients was 35 years; all had experienced at least two in vitro fertilization [IVF] failures due to “drastically impaired” embryonic development. None had achieved a pregnancy despite normal parental karyotypes and sperm DNA fragmentation rates.

The patients had their third and fourth IVF cycles performed with transfer and cryopreservation of pronuclear-stage embryos. Eight clinical pregnancies were obtained, representing a pregnancy rate of 29% and an implantation rate of 14%.

Data now have been collected for 50 patients—15 of whom have become pregnant, for a pregnancy rate of 27%.

“We were surprised ourselves since between all of these patients we had performed more than 180 cycles with absolutely no pregnancy,” she said.

No pregnancies have yet been reported from the cryopreserved embryos.

COPENHAGEN — Early embryo transfer on the first day after fertilization may remedy certain in vitro fertilization failures due to poor embryo quality, researchers reported in a poster presented at the annual meeting of the European Society of Human Reproduction and Embryology.

A subset of patients with good ovarian stimulation, egg quality, and fertilization have embryos that stop developing or exhibit extended fragmentation by their second day in culture, said Olia Anastasiou of the Laboratoire de VIF et de Biologie de la Reproduction at Hôpital Tenon in Paris.

“We have patients like this, most of whom have had three trials of [in vitro fertilization] with really bad quality embryos. It's been a real question mark what to do for them,” she said in an interview.

Prolonging embryo culture to the blastocyst stage (day 5) for such patients is a risk that usually results in no surviving embryos to transfer, she explained.

Her team's hypothesis was that certain maternal proteins, which are normally responsible for preimplantation embryo development, were deficient in these patients, making their embryos unable to survive the culture conditions in vitro.

For this group, they investigated the benefit of early embryo transfer at the pronuclear stage, just 1 day after fertilization.

A total of 27 patients were initially included in the study. The average age of the patients was 35 years; all had experienced at least two in vitro fertilization [IVF] failures due to “drastically impaired” embryonic development. None had achieved a pregnancy despite normal parental karyotypes and sperm DNA fragmentation rates.

The patients had their third and fourth IVF cycles performed with transfer and cryopreservation of pronuclear-stage embryos. Eight clinical pregnancies were obtained, representing a pregnancy rate of 29% and an implantation rate of 14%.

Data now have been collected for 50 patients—15 of whom have become pregnant, for a pregnancy rate of 27%.

“We were surprised ourselves since between all of these patients we had performed more than 180 cycles with absolutely no pregnancy,” she said.

No pregnancies have yet been reported from the cryopreserved embryos.

COPENHAGEN — Women who give birth after age 45 may have a special set of genes that makes them more fertile than average women, according to Israeli researchers.

“These women are models for us to learn about fertility,” Neri Laufer, M.D., said at the annual meeting of the European Society of Human Reproduction and Embryology.

Dr. Laufer of Hadassah University Medical Center, Jerusalem, outlined his work with more than 200 Ashkenazi Jewish women who had conceived spontaneously after the age of 45 (Fertil. Steril. 2004;81:1328–32).

“More than 80% of these women have six children or more and a low miscarriage rate,” he said.

Genetic profiling performed on eight of these women identified a clustering of genes that decreases apoptosis and increases DNA repair. The genes were not found in a control group of six women of the same age whose childbearing had ended at age 30.

“These women appear to differ from the normal population due to a unique genetic predisposition that protects them from the DNA damage and cellular aging that helps age the ovary,” Dr. Laufer said.

Preliminary work with a group of similarly fertile Bedouin women has identified the same genetic expression, he said at a news conference. Dr. Laufer said his team plans to study women from other ethnic/genetic groups to compare their genetic fingerprints. Identifying the presence or absence of this gene set could help doctors counsel women about their reproductive expectations, he said.

He added that the presence of genes linked to extended reproductive potential may indicate genetic capabilities to resist general aging. “What we don't yet know is, will these women also live longer?”

COPENHAGEN — Women who give birth after age 45 may have a special set of genes that makes them more fertile than average women, according to Israeli researchers.

“These women are models for us to learn about fertility,” Neri Laufer, M.D., said at the annual meeting of the European Society of Human Reproduction and Embryology.

Dr. Laufer of Hadassah University Medical Center, Jerusalem, outlined his work with more than 200 Ashkenazi Jewish women who had conceived spontaneously after the age of 45 (Fertil. Steril. 2004;81:1328–32).

“More than 80% of these women have six children or more and a low miscarriage rate,” he said.

Genetic profiling performed on eight of these women identified a clustering of genes that decreases apoptosis and increases DNA repair. The genes were not found in a control group of six women of the same age whose childbearing had ended at age 30.

“These women appear to differ from the normal population due to a unique genetic predisposition that protects them from the DNA damage and cellular aging that helps age the ovary,” Dr. Laufer said.

Preliminary work with a group of similarly fertile Bedouin women has identified the same genetic expression, he said at a news conference. Dr. Laufer said his team plans to study women from other ethnic/genetic groups to compare their genetic fingerprints. Identifying the presence or absence of this gene set could help doctors counsel women about their reproductive expectations, he said.

He added that the presence of genes linked to extended reproductive potential may indicate genetic capabilities to resist general aging. “What we don't yet know is, will these women also live longer?”

COPENHAGEN — Women who give birth after age 45 may have a special set of genes that makes them more fertile than average women, according to Israeli researchers.

“These women are models for us to learn about fertility,” Neri Laufer, M.D., said at the annual meeting of the European Society of Human Reproduction and Embryology.

Dr. Laufer of Hadassah University Medical Center, Jerusalem, outlined his work with more than 200 Ashkenazi Jewish women who had conceived spontaneously after the age of 45 (Fertil. Steril. 2004;81:1328–32).

“More than 80% of these women have six children or more and a low miscarriage rate,” he said.

Genetic profiling performed on eight of these women identified a clustering of genes that decreases apoptosis and increases DNA repair. The genes were not found in a control group of six women of the same age whose childbearing had ended at age 30.

“These women appear to differ from the normal population due to a unique genetic predisposition that protects them from the DNA damage and cellular aging that helps age the ovary,” Dr. Laufer said.

Preliminary work with a group of similarly fertile Bedouin women has identified the same genetic expression, he said at a news conference. Dr. Laufer said his team plans to study women from other ethnic/genetic groups to compare their genetic fingerprints. Identifying the presence or absence of this gene set could help doctors counsel women about their reproductive expectations, he said.

He added that the presence of genes linked to extended reproductive potential may indicate genetic capabilities to resist general aging. “What we don't yet know is, will these women also live longer?”

COPENHAGEN — The recent announcement of two births made possible by ovarian transplant procedures marks a new stage in the field of fertility restoration, raising ethical questions about whether such procedures should be made more widely available, according to Anthony Rutherford, M.D.

“Is it ethical now to start storing ovarian tissue for patients? Is this still experimental research or is it established clinical practice?” Dr. Rutherford, a consultant gynecologist at Leeds (England) General Infirmary, asked during a presentation at the annual meeting of the European Society for Human Reproduction and Embryology.

Experts in the field of ovarian transplant are divided about how the technology should be applied and who should undergo the procedure.

The majority of work in this area has focused on women who are about to undergo aggressive chemotherapy, which generally leads to infertility. These patients freeze their healthy ovarian tissue before having chemotherapy. Once their cancer is in remission, they can have small pieces of their ovarian tissue transplanted into them, a procedure known as autotransplantation.

This was the case with a 28-year-old Israeli woman who gave birth at the end of June after ovarian transplantation followed by in vitro fertilization (IVF), reported Dror Meirow, M.D., of Sheba Medical Center in Ramat Gan, Israel (http://content.nejm.org/cgi/reprint/NEJMc055237v1.pdf

A few weeks earlier, a baby was born to a 24-year-old U.S. woman with no history of chemotherapy (N. Engl. J. Med. 2005:353;58–63). This woman had experienced premature ovarian failure at age 14. Instead of receiving an autotransplant of her own ovarian tissue, she was the first recipient of an ovarian allograft, receiving tissue from her identical twin.

The choice by her surgeon, Saint Louis-based Sherman Silber, M.D., to extend fertility restoration beyond the realm of chemotherapy patients, to move from autotransplantation into allotransplantation, and to use a groundbreaking transplant technique, raises the question of opening access to such techniques to a wider population of women—and for more diverse reasons.

Until now, transplant efforts aimed at restoring ovarian function and ovulation have required IVF to achieve a pregnancy. But Dr. Silber's technique has eliminated the necessity of that expensive procedure, achieving the world's first human orthotopic ovarian transplant that allowed natural conception.

(The birth of a Belgian baby last year following an orthotopic ovarian transplant procedure and natural conception was questioned by some experts, since it could not be confirmed that she had ovulated from the transplanted ovarian tissue [Lancet 2004:364;1405–10]. Since her ovaries had been left in place, spontaneous ovulation could not be ruled out.)

From the points of view of Dr. Silber's sibling patients, ovarian transplant is a minimally invasive outpatient procedure—possibly giving the recipient years of potential for spontaneous conceptions.

Dr. Silber said that he believes the appeal of this more patient-friendly ovarian transplantation could be wide reaching, extending beyond autotransplants for chemotherapy patients and even beyond allotransplants for patients with premature ovarian failure. Dr. Silber has performed two additional ovarian transplants in two other twin sets since his first success, but to date there are no pregnancies.

He has already had requests from general infertility patients for allotransplants as an alternative to egg donation. (Some couples say they have no other choice for religious reasons.)

Dr. Silber said he sees the appeal of ovarian transplant extending to the general population who might choose ovarian tissue freezing and subsequent autotransplantation in the hopes of extending their biological clocks.

Dr. Rutherford expressed caution with regard to these advances. “We certainly need to be very careful about the patients that we select,” he said in an interview, adding that he feels it is premature to offer ovarian transplant for social rather than medical reasons.

And even for those patients who have medical reasons for wanting ovarian transplant, many physicians, including Dr. Rutherford, are hesitant to embrace the procedure as a routine clinical practice. “Are we giving false hope to vulnerable patients?” he asked.

Dr. Rutherford has called for the creation of a registry to keep track of all ovarian transplant cases and to follow them to assess the efficacy and safety of the procedure.

COPENHAGEN — The recent announcement of two births made possible by ovarian transplant procedures marks a new stage in the field of fertility restoration, raising ethical questions about whether such procedures should be made more widely available, according to Anthony Rutherford, M.D.

“Is it ethical now to start storing ovarian tissue for patients? Is this still experimental research or is it established clinical practice?” Dr. Rutherford, a consultant gynecologist at Leeds (England) General Infirmary, asked during a presentation at the annual meeting of the European Society for Human Reproduction and Embryology.

Experts in the field of ovarian transplant are divided about how the technology should be applied and who should undergo the procedure.

The majority of work in this area has focused on women who are about to undergo aggressive chemotherapy, which generally leads to infertility. These patients freeze their healthy ovarian tissue before having chemotherapy. Once their cancer is in remission, they can have small pieces of their ovarian tissue transplanted into them, a procedure known as autotransplantation.

This was the case with a 28-year-old Israeli woman who gave birth at the end of June after ovarian transplantation followed by in vitro fertilization (IVF), reported Dror Meirow, M.D., of Sheba Medical Center in Ramat Gan, Israel (http://content.nejm.org/cgi/reprint/NEJMc055237v1.pdf

A few weeks earlier, a baby was born to a 24-year-old U.S. woman with no history of chemotherapy (N. Engl. J. Med. 2005:353;58–63). This woman had experienced premature ovarian failure at age 14. Instead of receiving an autotransplant of her own ovarian tissue, she was the first recipient of an ovarian allograft, receiving tissue from her identical twin.

The choice by her surgeon, Saint Louis-based Sherman Silber, M.D., to extend fertility restoration beyond the realm of chemotherapy patients, to move from autotransplantation into allotransplantation, and to use a groundbreaking transplant technique, raises the question of opening access to such techniques to a wider population of women—and for more diverse reasons.

Until now, transplant efforts aimed at restoring ovarian function and ovulation have required IVF to achieve a pregnancy. But Dr. Silber's technique has eliminated the necessity of that expensive procedure, achieving the world's first human orthotopic ovarian transplant that allowed natural conception.

(The birth of a Belgian baby last year following an orthotopic ovarian transplant procedure and natural conception was questioned by some experts, since it could not be confirmed that she had ovulated from the transplanted ovarian tissue [Lancet 2004:364;1405–10]. Since her ovaries had been left in place, spontaneous ovulation could not be ruled out.)

From the points of view of Dr. Silber's sibling patients, ovarian transplant is a minimally invasive outpatient procedure—possibly giving the recipient years of potential for spontaneous conceptions.

Dr. Silber said that he believes the appeal of this more patient-friendly ovarian transplantation could be wide reaching, extending beyond autotransplants for chemotherapy patients and even beyond allotransplants for patients with premature ovarian failure. Dr. Silber has performed two additional ovarian transplants in two other twin sets since his first success, but to date there are no pregnancies.

He has already had requests from general infertility patients for allotransplants as an alternative to egg donation. (Some couples say they have no other choice for religious reasons.)

Dr. Silber said he sees the appeal of ovarian transplant extending to the general population who might choose ovarian tissue freezing and subsequent autotransplantation in the hopes of extending their biological clocks.

Dr. Rutherford expressed caution with regard to these advances. “We certainly need to be very careful about the patients that we select,” he said in an interview, adding that he feels it is premature to offer ovarian transplant for social rather than medical reasons.

And even for those patients who have medical reasons for wanting ovarian transplant, many physicians, including Dr. Rutherford, are hesitant to embrace the procedure as a routine clinical practice. “Are we giving false hope to vulnerable patients?” he asked.

Dr. Rutherford has called for the creation of a registry to keep track of all ovarian transplant cases and to follow them to assess the efficacy and safety of the procedure.

COPENHAGEN — The recent announcement of two births made possible by ovarian transplant procedures marks a new stage in the field of fertility restoration, raising ethical questions about whether such procedures should be made more widely available, according to Anthony Rutherford, M.D.

“Is it ethical now to start storing ovarian tissue for patients? Is this still experimental research or is it established clinical practice?” Dr. Rutherford, a consultant gynecologist at Leeds (England) General Infirmary, asked during a presentation at the annual meeting of the European Society for Human Reproduction and Embryology.

Experts in the field of ovarian transplant are divided about how the technology should be applied and who should undergo the procedure.

The majority of work in this area has focused on women who are about to undergo aggressive chemotherapy, which generally leads to infertility. These patients freeze their healthy ovarian tissue before having chemotherapy. Once their cancer is in remission, they can have small pieces of their ovarian tissue transplanted into them, a procedure known as autotransplantation.

This was the case with a 28-year-old Israeli woman who gave birth at the end of June after ovarian transplantation followed by in vitro fertilization (IVF), reported Dror Meirow, M.D., of Sheba Medical Center in Ramat Gan, Israel (http://content.nejm.org/cgi/reprint/NEJMc055237v1.pdf

A few weeks earlier, a baby was born to a 24-year-old U.S. woman with no history of chemotherapy (N. Engl. J. Med. 2005:353;58–63). This woman had experienced premature ovarian failure at age 14. Instead of receiving an autotransplant of her own ovarian tissue, she was the first recipient of an ovarian allograft, receiving tissue from her identical twin.

The choice by her surgeon, Saint Louis-based Sherman Silber, M.D., to extend fertility restoration beyond the realm of chemotherapy patients, to move from autotransplantation into allotransplantation, and to use a groundbreaking transplant technique, raises the question of opening access to such techniques to a wider population of women—and for more diverse reasons.

Until now, transplant efforts aimed at restoring ovarian function and ovulation have required IVF to achieve a pregnancy. But Dr. Silber's technique has eliminated the necessity of that expensive procedure, achieving the world's first human orthotopic ovarian transplant that allowed natural conception.

(The birth of a Belgian baby last year following an orthotopic ovarian transplant procedure and natural conception was questioned by some experts, since it could not be confirmed that she had ovulated from the transplanted ovarian tissue [Lancet 2004:364;1405–10]. Since her ovaries had been left in place, spontaneous ovulation could not be ruled out.)

From the points of view of Dr. Silber's sibling patients, ovarian transplant is a minimally invasive outpatient procedure—possibly giving the recipient years of potential for spontaneous conceptions.

Dr. Silber said that he believes the appeal of this more patient-friendly ovarian transplantation could be wide reaching, extending beyond autotransplants for chemotherapy patients and even beyond allotransplants for patients with premature ovarian failure. Dr. Silber has performed two additional ovarian transplants in two other twin sets since his first success, but to date there are no pregnancies.

He has already had requests from general infertility patients for allotransplants as an alternative to egg donation. (Some couples say they have no other choice for religious reasons.)

Dr. Silber said he sees the appeal of ovarian transplant extending to the general population who might choose ovarian tissue freezing and subsequent autotransplantation in the hopes of extending their biological clocks.

Dr. Rutherford expressed caution with regard to these advances. “We certainly need to be very careful about the patients that we select,” he said in an interview, adding that he feels it is premature to offer ovarian transplant for social rather than medical reasons.

And even for those patients who have medical reasons for wanting ovarian transplant, many physicians, including Dr. Rutherford, are hesitant to embrace the procedure as a routine clinical practice. “Are we giving false hope to vulnerable patients?” he asked.

Dr. Rutherford has called for the creation of a registry to keep track of all ovarian transplant cases and to follow them to assess the efficacy and safety of the procedure.

Two recent births made possible through maternal ovarian transplant procedures were the result of markedly different techniques and approaches.

U.S. expert Sherman Silber, M.D., of St. Luke's Hospital, St. Louis, performed an ovarian allotransplant between 24-year-old identical twins, one of whom had premature ovarian failure. The procedure restored the patient's fertility and her ability to conceive naturally (N. Engl. J. Med. 2005;353:58–63).

In Israel, the transplant performed by Dror Meirow, M.D., of Chaim Sheba Medical Center in Tel Hashomer, and colleagues was an autotransplant of a 28-year-old cancer patient's previously frozen healthy ovarian tissue. Conception was achieved through in vitro fertilization (N. Engl. J. Med. 2005;353:318–21).

In the U.S. patient, a woman who had experienced premature ovarian failure at age 14, laparoscopic examination and ovarian biopsy showed atrophic, elongated (“streak”) gonads with no follicles and a small uterus with an otherwise normal reproductive tract. Her donor sister had three children who had been conceived naturally, and she had been using oral contraception in the year preceding the procedure.

The donor's ovary was laparoscopically removed, and the cortical tissue was dissected ex vivo. Meanwhile, the recipient underwent a minilaparotomy during which the cortex of each streak ovary was resected, exposing the raw surface of the medulla.

Hemostasis was controlled with pinpoint microbipolar forceps and continuous irrigation with heparin-treated saline to prevent the formation of a hematoma under the graft.

One-third of the donor ovary was sutured onto the raw medulla of each recipient ovary, and the remaining third was frozen. Analysis of spare tissue from the recipient's ovaries confirmed that there was extensive fibrosis and that there were no follicles.

Both sisters returned home 1 day after the procedure.

At 71 days after transplantation, a 14-mm follicle was observed in the recipient, her serum estradiol level was 154 pg/mL, and her uterine lining was 8 mm thick. Her first postoperative menses occurred at 80 days, although it lasted only a single day. Her ovaries remained quiescent until 128 days after the procedure when another 14-mm follicle was observed. At 142 days after the procedure, she had a heavy menstrual period.

On day 26 of her second menstrual cycle, her β-hCG level (828 mIU/mL) indicated that she was pregnant, and 5 weeks after her second menstrual period, a normal intrauterine pregnancy was confirmed by ultrasound. She gave birth vaginally to a healthy infant at 38 weeks' gestation.

“It is extremely unlikely that the restoration of ovarian function in this patient after transplantation was due to residual follicles in the streak ovary of the recipient,” Dr. Silber and his associates wrote. “She had a decade-long history of amenorrhea with elevated gonadotropin levels on all occasions on which they were measured and no detectable follicles on pathologic examination.”

The Israeli transplant patient had experienced ovarian failure after high-dose chemotherapy for non-Hodgkin's lymphoma. Ovarian tissue containing many primordial follicles was harvested and frozen before she underwent high-dose chemotherapy but after she had undergone a second-line conventional chemotherapy regimen.

The patient remained free of disease 24 months after undergoing chemotherapy, at which point she requested autotransplantation of the thawed ovarian tissue. Strips of the tissue were transplanted to the left ovary, and small fragments were injected into the right ovary. Menstruation resumed spontaneously 8 months later, and baseline levels of antimüllerian hormone, which were previously undetectable (consistent with ovarian failure), were high—consistent with the presence of active follicles in an early stage of growth. This was followed by a rise in inhibin B to levels reported in ovulatory women. Ultrasonography revealed a preovulatory follicle in the left ovary.

The next month, another spontaneous menstrual period occurred, after which modified natural-cycle in vitro fertilization was performed. A single egg was retrieved and fertilized, and a four-cell embryo was transferred to the uterus. A healthy infant was delivered by cesarean section at 38 weeks' gestation.

“Although we cannot rule out the possibility that the egg was derived from the native ovary, we consider this possibility very unlikely, given the consistent evidence of ovarian failure after high-dose chemotherapy and the timing of restoration of ovarian function after transplantation,” they reported.

Two recent births made possible through maternal ovarian transplant procedures were the result of markedly different techniques and approaches.

U.S. expert Sherman Silber, M.D., of St. Luke's Hospital, St. Louis, performed an ovarian allotransplant between 24-year-old identical twins, one of whom had premature ovarian failure. The procedure restored the patient's fertility and her ability to conceive naturally (N. Engl. J. Med. 2005;353:58–63).

In Israel, the transplant performed by Dror Meirow, M.D., of Chaim Sheba Medical Center in Tel Hashomer, and colleagues was an autotransplant of a 28-year-old cancer patient's previously frozen healthy ovarian tissue. Conception was achieved through in vitro fertilization (N. Engl. J. Med. 2005;353:318–21).

In the U.S. patient, a woman who had experienced premature ovarian failure at age 14, laparoscopic examination and ovarian biopsy showed atrophic, elongated (“streak”) gonads with no follicles and a small uterus with an otherwise normal reproductive tract. Her donor sister had three children who had been conceived naturally, and she had been using oral contraception in the year preceding the procedure.

The donor's ovary was laparoscopically removed, and the cortical tissue was dissected ex vivo. Meanwhile, the recipient underwent a minilaparotomy during which the cortex of each streak ovary was resected, exposing the raw surface of the medulla.

Hemostasis was controlled with pinpoint microbipolar forceps and continuous irrigation with heparin-treated saline to prevent the formation of a hematoma under the graft.

One-third of the donor ovary was sutured onto the raw medulla of each recipient ovary, and the remaining third was frozen. Analysis of spare tissue from the recipient's ovaries confirmed that there was extensive fibrosis and that there were no follicles.

Both sisters returned home 1 day after the procedure.

At 71 days after transplantation, a 14-mm follicle was observed in the recipient, her serum estradiol level was 154 pg/mL, and her uterine lining was 8 mm thick. Her first postoperative menses occurred at 80 days, although it lasted only a single day. Her ovaries remained quiescent until 128 days after the procedure when another 14-mm follicle was observed. At 142 days after the procedure, she had a heavy menstrual period.

On day 26 of her second menstrual cycle, her β-hCG level (828 mIU/mL) indicated that she was pregnant, and 5 weeks after her second menstrual period, a normal intrauterine pregnancy was confirmed by ultrasound. She gave birth vaginally to a healthy infant at 38 weeks' gestation.

“It is extremely unlikely that the restoration of ovarian function in this patient after transplantation was due to residual follicles in the streak ovary of the recipient,” Dr. Silber and his associates wrote. “She had a decade-long history of amenorrhea with elevated gonadotropin levels on all occasions on which they were measured and no detectable follicles on pathologic examination.”

The Israeli transplant patient had experienced ovarian failure after high-dose chemotherapy for non-Hodgkin's lymphoma. Ovarian tissue containing many primordial follicles was harvested and frozen before she underwent high-dose chemotherapy but after she had undergone a second-line conventional chemotherapy regimen.

The patient remained free of disease 24 months after undergoing chemotherapy, at which point she requested autotransplantation of the thawed ovarian tissue. Strips of the tissue were transplanted to the left ovary, and small fragments were injected into the right ovary. Menstruation resumed spontaneously 8 months later, and baseline levels of antimüllerian hormone, which were previously undetectable (consistent with ovarian failure), were high—consistent with the presence of active follicles in an early stage of growth. This was followed by a rise in inhibin B to levels reported in ovulatory women. Ultrasonography revealed a preovulatory follicle in the left ovary.

The next month, another spontaneous menstrual period occurred, after which modified natural-cycle in vitro fertilization was performed. A single egg was retrieved and fertilized, and a four-cell embryo was transferred to the uterus. A healthy infant was delivered by cesarean section at 38 weeks' gestation.

“Although we cannot rule out the possibility that the egg was derived from the native ovary, we consider this possibility very unlikely, given the consistent evidence of ovarian failure after high-dose chemotherapy and the timing of restoration of ovarian function after transplantation,” they reported.

Two recent births made possible through maternal ovarian transplant procedures were the result of markedly different techniques and approaches.

U.S. expert Sherman Silber, M.D., of St. Luke's Hospital, St. Louis, performed an ovarian allotransplant between 24-year-old identical twins, one of whom had premature ovarian failure. The procedure restored the patient's fertility and her ability to conceive naturally (N. Engl. J. Med. 2005;353:58–63).

In Israel, the transplant performed by Dror Meirow, M.D., of Chaim Sheba Medical Center in Tel Hashomer, and colleagues was an autotransplant of a 28-year-old cancer patient's previously frozen healthy ovarian tissue. Conception was achieved through in vitro fertilization (N. Engl. J. Med. 2005;353:318–21).

In the U.S. patient, a woman who had experienced premature ovarian failure at age 14, laparoscopic examination and ovarian biopsy showed atrophic, elongated (“streak”) gonads with no follicles and a small uterus with an otherwise normal reproductive tract. Her donor sister had three children who had been conceived naturally, and she had been using oral contraception in the year preceding the procedure.

The donor's ovary was laparoscopically removed, and the cortical tissue was dissected ex vivo. Meanwhile, the recipient underwent a minilaparotomy during which the cortex of each streak ovary was resected, exposing the raw surface of the medulla.

Hemostasis was controlled with pinpoint microbipolar forceps and continuous irrigation with heparin-treated saline to prevent the formation of a hematoma under the graft.

One-third of the donor ovary was sutured onto the raw medulla of each recipient ovary, and the remaining third was frozen. Analysis of spare tissue from the recipient's ovaries confirmed that there was extensive fibrosis and that there were no follicles.

Both sisters returned home 1 day after the procedure.

At 71 days after transplantation, a 14-mm follicle was observed in the recipient, her serum estradiol level was 154 pg/mL, and her uterine lining was 8 mm thick. Her first postoperative menses occurred at 80 days, although it lasted only a single day. Her ovaries remained quiescent until 128 days after the procedure when another 14-mm follicle was observed. At 142 days after the procedure, she had a heavy menstrual period.

On day 26 of her second menstrual cycle, her β-hCG level (828 mIU/mL) indicated that she was pregnant, and 5 weeks after her second menstrual period, a normal intrauterine pregnancy was confirmed by ultrasound. She gave birth vaginally to a healthy infant at 38 weeks' gestation.

“It is extremely unlikely that the restoration of ovarian function in this patient after transplantation was due to residual follicles in the streak ovary of the recipient,” Dr. Silber and his associates wrote. “She had a decade-long history of amenorrhea with elevated gonadotropin levels on all occasions on which they were measured and no detectable follicles on pathologic examination.”

The Israeli transplant patient had experienced ovarian failure after high-dose chemotherapy for non-Hodgkin's lymphoma. Ovarian tissue containing many primordial follicles was harvested and frozen before she underwent high-dose chemotherapy but after she had undergone a second-line conventional chemotherapy regimen.

The patient remained free of disease 24 months after undergoing chemotherapy, at which point she requested autotransplantation of the thawed ovarian tissue. Strips of the tissue were transplanted to the left ovary, and small fragments were injected into the right ovary. Menstruation resumed spontaneously 8 months later, and baseline levels of antimüllerian hormone, which were previously undetectable (consistent with ovarian failure), were high—consistent with the presence of active follicles in an early stage of growth. This was followed by a rise in inhibin B to levels reported in ovulatory women. Ultrasonography revealed a preovulatory follicle in the left ovary.

The next month, another spontaneous menstrual period occurred, after which modified natural-cycle in vitro fertilization was performed. A single egg was retrieved and fertilized, and a four-cell embryo was transferred to the uterus. A healthy infant was delivered by cesarean section at 38 weeks' gestation.

“Although we cannot rule out the possibility that the egg was derived from the native ovary, we consider this possibility very unlikely, given the consistent evidence of ovarian failure after high-dose chemotherapy and the timing of restoration of ovarian function after transplantation,” they reported.

COPENHAGEN — The science is the same, but when it comes to the approach, European and U.S. fertility treatments are starting to branch out in different directions.

The latest (2002) figures from the European IVF Monitoring Program, which includes data from 24 countries, show that the overall pregnancy rate per transfer for in vitro fertilization (IVF) and intracytoplasmic sperm injection is just below 30%, compared with about 35% in the United States, reported Dr. Anders Nyboe Andersen at the annual meeting of the European Society of Human Reproduction and Embryology.

But where the Europeans really differ is in their multiple birth rate—which already is significantly lower than that of the United States and is falling faster.

Of all IVF births in Europe in 2002, 1.3% were triplet births, down from 3.6% in 1997. That's in stark contrast to the U.S. rate, which currently is 3.8%, down from 7% in 1996.

But it is the rate of twins in IVF births that fertility experts focus on most. That rate stands at 23.6% in Europe, compared with 31.6% in the United States.

The widespread adoption of elective single embryo transfer (eSET) in Europe is the driving force behind the lower multiple pregnancy rate, commented Dr. Andersen, coordinator of the European IVF Monitoring Program and head of the fertility clinic at the Rigshospitalet at Copenhagen University Hospital.

Although there is a wide variation in embryo transfer policies across European countries, 70% of all European embryo transfers involved just one or two embryos in 2002. After 2003, when the Swedish government legislated further restrictions, 70% of all Swedish transfers were elective single embryo transfers, reported Dr. Karl Nygren, an ob.gyn. at Sofiahemmet Hospital in Stockholm.

In the United States in 2002, the eSET rate was 1.2%, up from 0.8% the year before, according to Eric S. Surrey, M.D., president of the Society for Assisted Reproductive Technology (SART).

Recent guidelines released by the American Society for Reproductive Medicine, of which SART is an affiliate, suggest that priority for eSET should be given to patients with “the most favorable prognosis” (Fertil. Steril. 2004;82:773–4), and it is important to consider that the most recent eSET figures predate the new guidelines, Dr. Surrey told this newspaper.

“Any impact of this recommendation would not be seen until the 2005 outcome data,” he said. At the meeting, when Dr. Andersen was asked why IVF birth rates remain consistently higher in the United States than in Europe, he said that it is too easy to focus exclusively on the fact that Americans transfer more embryos.

“We have to face the fact that they are doing a pretty good job,” he told delegates at the meeting.

A key advantage to the U.S. approach is the trend toward smaller and more highly specialized clinics, where doctors can take a lot of time with each patient. “Perhaps Europe could learn from the United States in this regard,” he said.

ICSI Procedures Rise in Europe

For the first time in Europe, the number of intracytoplasmic sperm injection cycles exceeded regular IVF cycles; ICSI was used in 52% of all IVF cycles in 2002.

This is similar to the U.S. situation in which ICSI is used in 53% of cycles.

There are probably many reasons for the shift. “One of them could be that the relative causes of infertility are shifting,” Dr. Andersen said.

There are now fewer severe tubal problems because of better protection against STDs, while there is growing evidence male subfertility may be increasing as a result of environmental pollutants, he said. Also, many couples who previously might have used artificial insemination with donor sperm are now opting for ICSI.

Finally, since the procedure was first introduced in 1992, clinics have become more familiar and more skilled at performing it, thus making it more widely available.

COPENHAGEN — The science is the same, but when it comes to the approach, European and U.S. fertility treatments are starting to branch out in different directions.

The latest (2002) figures from the European IVF Monitoring Program, which includes data from 24 countries, show that the overall pregnancy rate per transfer for in vitro fertilization (IVF) and intracytoplasmic sperm injection is just below 30%, compared with about 35% in the United States, reported Dr. Anders Nyboe Andersen at the annual meeting of the European Society of Human Reproduction and Embryology.

But where the Europeans really differ is in their multiple birth rate—which already is significantly lower than that of the United States and is falling faster.

Of all IVF births in Europe in 2002, 1.3% were triplet births, down from 3.6% in 1997. That's in stark contrast to the U.S. rate, which currently is 3.8%, down from 7% in 1996.

But it is the rate of twins in IVF births that fertility experts focus on most. That rate stands at 23.6% in Europe, compared with 31.6% in the United States.

The widespread adoption of elective single embryo transfer (eSET) in Europe is the driving force behind the lower multiple pregnancy rate, commented Dr. Andersen, coordinator of the European IVF Monitoring Program and head of the fertility clinic at the Rigshospitalet at Copenhagen University Hospital.

Although there is a wide variation in embryo transfer policies across European countries, 70% of all European embryo transfers involved just one or two embryos in 2002. After 2003, when the Swedish government legislated further restrictions, 70% of all Swedish transfers were elective single embryo transfers, reported Dr. Karl Nygren, an ob.gyn. at Sofiahemmet Hospital in Stockholm.

In the United States in 2002, the eSET rate was 1.2%, up from 0.8% the year before, according to Eric S. Surrey, M.D., president of the Society for Assisted Reproductive Technology (SART).

Recent guidelines released by the American Society for Reproductive Medicine, of which SART is an affiliate, suggest that priority for eSET should be given to patients with “the most favorable prognosis” (Fertil. Steril. 2004;82:773–4), and it is important to consider that the most recent eSET figures predate the new guidelines, Dr. Surrey told this newspaper.

“Any impact of this recommendation would not be seen until the 2005 outcome data,” he said. At the meeting, when Dr. Andersen was asked why IVF birth rates remain consistently higher in the United States than in Europe, he said that it is too easy to focus exclusively on the fact that Americans transfer more embryos.

“We have to face the fact that they are doing a pretty good job,” he told delegates at the meeting.

A key advantage to the U.S. approach is the trend toward smaller and more highly specialized clinics, where doctors can take a lot of time with each patient. “Perhaps Europe could learn from the United States in this regard,” he said.

ICSI Procedures Rise in Europe

For the first time in Europe, the number of intracytoplasmic sperm injection cycles exceeded regular IVF cycles; ICSI was used in 52% of all IVF cycles in 2002.

This is similar to the U.S. situation in which ICSI is used in 53% of cycles.

There are probably many reasons for the shift. “One of them could be that the relative causes of infertility are shifting,” Dr. Andersen said.

There are now fewer severe tubal problems because of better protection against STDs, while there is growing evidence male subfertility may be increasing as a result of environmental pollutants, he said. Also, many couples who previously might have used artificial insemination with donor sperm are now opting for ICSI.

Finally, since the procedure was first introduced in 1992, clinics have become more familiar and more skilled at performing it, thus making it more widely available.

COPENHAGEN — The science is the same, but when it comes to the approach, European and U.S. fertility treatments are starting to branch out in different directions.

The latest (2002) figures from the European IVF Monitoring Program, which includes data from 24 countries, show that the overall pregnancy rate per transfer for in vitro fertilization (IVF) and intracytoplasmic sperm injection is just below 30%, compared with about 35% in the United States, reported Dr. Anders Nyboe Andersen at the annual meeting of the European Society of Human Reproduction and Embryology.

But where the Europeans really differ is in their multiple birth rate—which already is significantly lower than that of the United States and is falling faster.

Of all IVF births in Europe in 2002, 1.3% were triplet births, down from 3.6% in 1997. That's in stark contrast to the U.S. rate, which currently is 3.8%, down from 7% in 1996.

But it is the rate of twins in IVF births that fertility experts focus on most. That rate stands at 23.6% in Europe, compared with 31.6% in the United States.

The widespread adoption of elective single embryo transfer (eSET) in Europe is the driving force behind the lower multiple pregnancy rate, commented Dr. Andersen, coordinator of the European IVF Monitoring Program and head of the fertility clinic at the Rigshospitalet at Copenhagen University Hospital.

Although there is a wide variation in embryo transfer policies across European countries, 70% of all European embryo transfers involved just one or two embryos in 2002. After 2003, when the Swedish government legislated further restrictions, 70% of all Swedish transfers were elective single embryo transfers, reported Dr. Karl Nygren, an ob.gyn. at Sofiahemmet Hospital in Stockholm.

In the United States in 2002, the eSET rate was 1.2%, up from 0.8% the year before, according to Eric S. Surrey, M.D., president of the Society for Assisted Reproductive Technology (SART).

Recent guidelines released by the American Society for Reproductive Medicine, of which SART is an affiliate, suggest that priority for eSET should be given to patients with “the most favorable prognosis” (Fertil. Steril. 2004;82:773–4), and it is important to consider that the most recent eSET figures predate the new guidelines, Dr. Surrey told this newspaper.

“Any impact of this recommendation would not be seen until the 2005 outcome data,” he said. At the meeting, when Dr. Andersen was asked why IVF birth rates remain consistently higher in the United States than in Europe, he said that it is too easy to focus exclusively on the fact that Americans transfer more embryos.

“We have to face the fact that they are doing a pretty good job,” he told delegates at the meeting.

A key advantage to the U.S. approach is the trend toward smaller and more highly specialized clinics, where doctors can take a lot of time with each patient. “Perhaps Europe could learn from the United States in this regard,” he said.

ICSI Procedures Rise in Europe

For the first time in Europe, the number of intracytoplasmic sperm injection cycles exceeded regular IVF cycles; ICSI was used in 52% of all IVF cycles in 2002.

This is similar to the U.S. situation in which ICSI is used in 53% of cycles.

There are probably many reasons for the shift. “One of them could be that the relative causes of infertility are shifting,” Dr. Andersen said.

There are now fewer severe tubal problems because of better protection against STDs, while there is growing evidence male subfertility may be increasing as a result of environmental pollutants, he said. Also, many couples who previously might have used artificial insemination with donor sperm are now opting for ICSI.

Finally, since the procedure was first introduced in 1992, clinics have become more familiar and more skilled at performing it, thus making it more widely available.