Jane Salodof MacNeil

PHOENIX, ARIZ. — Adding Botox therapy to cosmetic dermatologic treatments can "extend the results for virtually everything we do," Jean Carruthers, M.D., said at a clinical dermatology conference sponsored by Medicis.

Clinical studies have already shown that combining botulinum toxin type A with broadband light therapy and with nonanimal stabilized hyaluronic acid can produce better results than a single therapy, reported Dr. Carruthers, an ophthalmology professor at the University of British Columbia, Vancouver.

"It makes so much sense to use them together," she said of Botox and Restylane, a nonanimal stabilized hyaluronic acid filler approved for use in the United States. "Botox halts active frown, and Restylane helps the dermis."

Dr. Carruthers cited a prospective study she conducted with her husband Alaistair Carruthers, B.M., of the same university. They randomized 38 adult females with moderate to severe glabellar wrinkles into two cohorts for a comparison of Restylane therapy alone with Restylane plus Botox.

The investigators reported that the women given both treatments "showed a better response both at rest and on maximal frown." The combination treatment also lasted longer. Median time to preinjection furrow status was 32 weeks for the combination patients, compared with 18 weeks for those treated only with the filler (Dermatol. Surg. 2003;29:802–9).

In another study, they randomized 30 women with moderate to severe crow's feet to two groups: one treated only with broadband light therapy and the other to light therapy plus Botox treatment. For this experiment they used Intense Pulsed Light from Lumenis Ltd. of Yokneam, Israel.

The Carruthers reported that all patients showed improvement when their faces were at rest and smiling, but the patients given both treatments improved more. Skin biopsies revealed an increase in dermal collagen for both groups. The researchers also reported improvements in lentigines, telangiectasia, and skin texture (Dermatol. Surg. 2004;30:355–6).

Dr. Carruthers called the synergy with the light system exciting. "Does IPL [intense pulsed light] stimulate new dermal collagen deposition?" she asked. "Does Botox stimulate new collagen formation in the dermis? Is it just IPL, or is Botox additive?"

Dr. Carruthers' commercial disclosures include Allergan, maker of Botox; Medicis Pharmaceuticals, distributor of Restylane; and Lumenis. She said she is a consultant to and investor in Allergan.

PHOENIX, ARIZ. — Adding Botox therapy to cosmetic dermatologic treatments can "extend the results for virtually everything we do," Jean Carruthers, M.D., said at a clinical dermatology conference sponsored by Medicis.

Clinical studies have already shown that combining botulinum toxin type A with broadband light therapy and with nonanimal stabilized hyaluronic acid can produce better results than a single therapy, reported Dr. Carruthers, an ophthalmology professor at the University of British Columbia, Vancouver.

"It makes so much sense to use them together," she said of Botox and Restylane, a nonanimal stabilized hyaluronic acid filler approved for use in the United States. "Botox halts active frown, and Restylane helps the dermis."

Dr. Carruthers cited a prospective study she conducted with her husband Alaistair Carruthers, B.M., of the same university. They randomized 38 adult females with moderate to severe glabellar wrinkles into two cohorts for a comparison of Restylane therapy alone with Restylane plus Botox.

The investigators reported that the women given both treatments "showed a better response both at rest and on maximal frown." The combination treatment also lasted longer. Median time to preinjection furrow status was 32 weeks for the combination patients, compared with 18 weeks for those treated only with the filler (Dermatol. Surg. 2003;29:802–9).

In another study, they randomized 30 women with moderate to severe crow's feet to two groups: one treated only with broadband light therapy and the other to light therapy plus Botox treatment. For this experiment they used Intense Pulsed Light from Lumenis Ltd. of Yokneam, Israel.

The Carruthers reported that all patients showed improvement when their faces were at rest and smiling, but the patients given both treatments improved more. Skin biopsies revealed an increase in dermal collagen for both groups. The researchers also reported improvements in lentigines, telangiectasia, and skin texture (Dermatol. Surg. 2004;30:355–6).

Dr. Carruthers called the synergy with the light system exciting. "Does IPL [intense pulsed light] stimulate new dermal collagen deposition?" she asked. "Does Botox stimulate new collagen formation in the dermis? Is it just IPL, or is Botox additive?"

Dr. Carruthers' commercial disclosures include Allergan, maker of Botox; Medicis Pharmaceuticals, distributor of Restylane; and Lumenis. She said she is a consultant to and investor in Allergan.

PHOENIX, ARIZ. — Adding Botox therapy to cosmetic dermatologic treatments can "extend the results for virtually everything we do," Jean Carruthers, M.D., said at a clinical dermatology conference sponsored by Medicis.

Clinical studies have already shown that combining botulinum toxin type A with broadband light therapy and with nonanimal stabilized hyaluronic acid can produce better results than a single therapy, reported Dr. Carruthers, an ophthalmology professor at the University of British Columbia, Vancouver.

"It makes so much sense to use them together," she said of Botox and Restylane, a nonanimal stabilized hyaluronic acid filler approved for use in the United States. "Botox halts active frown, and Restylane helps the dermis."

Dr. Carruthers cited a prospective study she conducted with her husband Alaistair Carruthers, B.M., of the same university. They randomized 38 adult females with moderate to severe glabellar wrinkles into two cohorts for a comparison of Restylane therapy alone with Restylane plus Botox.

The investigators reported that the women given both treatments "showed a better response both at rest and on maximal frown." The combination treatment also lasted longer. Median time to preinjection furrow status was 32 weeks for the combination patients, compared with 18 weeks for those treated only with the filler (Dermatol. Surg. 2003;29:802–9).

In another study, they randomized 30 women with moderate to severe crow's feet to two groups: one treated only with broadband light therapy and the other to light therapy plus Botox treatment. For this experiment they used Intense Pulsed Light from Lumenis Ltd. of Yokneam, Israel.

The Carruthers reported that all patients showed improvement when their faces were at rest and smiling, but the patients given both treatments improved more. Skin biopsies revealed an increase in dermal collagen for both groups. The researchers also reported improvements in lentigines, telangiectasia, and skin texture (Dermatol. Surg. 2004;30:355–6).

Dr. Carruthers called the synergy with the light system exciting. "Does IPL [intense pulsed light] stimulate new dermal collagen deposition?" she asked. "Does Botox stimulate new collagen formation in the dermis? Is it just IPL, or is Botox additive?"

Dr. Carruthers' commercial disclosures include Allergan, maker of Botox; Medicis Pharmaceuticals, distributor of Restylane; and Lumenis. She said she is a consultant to and investor in Allergan.

PHOENIX, ARIZ. — The lip that is enhanced with filler should meet definable proportions and yet retain its individuality, Arnold W. Klein, M.D., said at a clinical dermatology conference sponsored by Medicis.

"Lips are about volume but more importantly shape. Any enhancement must be undetectable," said Dr. Klein, who holds a dermatology chair in his name at the University of California, Los Angeles' David Geffen School of Medicine.

Lip augmentation requires fillers to increase facial volume in a subtle and aesthetically pleasing manner, he said. It is not about "simply eradicating lines."

The lower third of the aging face, including the lip, is the area least amenable to plastic surgery. Along with the thinning of both lips, he cited prominent labial mandibular grooves, the ends of the upper lips hanging down, loss of bone support from dentition and from the mandible, and decreased vertical support, he said.

According to Dr. Klein's formulation of the aesthetic lip: "The length of the closed, relaxed mouth should equal the distance between the medial aspect of the irises in the well-proportioned face." In addition, the ratio of the upper lip to the lower lip should be 1:1.6.

When the head is photographed in a postural position with a relaxed mouth, an interpupillary line drawn horizontally across the eyes should be parallel to a horizontal commissural line drawn where the lips meet.

Dr. Klein cited other characteristic facial landmarks including curvature of the dorsum and angulation of the nose. He said the base of the nose should be 18–20 mm above the upper lip, whereas the recommended distance between the lower lip and the chin is 36 mm.

Looking at the postural head position in profile, the physician should make sure both lips touch the "Steiner line," he said.

When seen in profile, the nasolabial angle should be about 84–105 degrees, he continued: "You want a good nasolabial angle."

To illustrate this, he showed a photograph in which one extended line connected the base of the nose to the tip of the nose. A second line from the base of the nose touched the "Glogau-Klein point" at the center edge of the upper lip. The angle is formed where the two lines intersect.

The G-K point describes the "ski slope" shape of the lip in profile as you move from the skin above the lip down onto the pink vermillion. There is always a little upturn, a point of reflection, which becomes lost as one ages, Richard G. Glogau, M.D., told SKIN & ALLERGY NEWS.

The cosmetic implication is that you have to recreate this shape with fillers used in the border of the lip to make the lip young and attractive. Also, if you use too much Botox on the upper lip, the orbicularis muscle flattens and makes an older looking lip. Therefore, it is generally a good idea to combine fillers with the Botox if you are trying to reestablish a youthful looking upper lip, said Dr. Glogau, who is a consultant to Allergan Inc., Medicis, and Inamed Aesthetics.

Dr. Klein cited a study of 100 women which showed that aging lips lose height (Dermatology 2004;208:307–13). He said the most important aspect of lip augmentation involves building buttresses to restore the lost height and the ends of the lips.

"You want flying buttresses to hold up the lips because of the loss of dentition," he said. "You want to restore the ends and build buttresses to support the lip. That's really important."

The choice of filling agent is less important than the physician's skill in using it, according to Dr. Klein, who disclosed ties as a consultant and/or investigator for Allergan Inc., Genzyme, Inamed Aesthetics, Anika Inc., Medicis, SkinMedica, and OrthoNeutrogena.

"It is not what you use. It is how you use it," he said, recommending physicians become really skilled in one or two products rather than plow through what he described as a delicatessen menu of filling agents on the market.

Except for correction of scars, Dr. Klein opposes the use of permanent fillers. He warned that these agents could become increasingly visible or create an unnatural appearance as facial contours change over time. "For aesthetic indications I believe permanent fillers are a formula for disaster," he said.

The Glogau-Klein point shows dimensions of the aesthetic lip. Courtesy Dr. Richard G. Glogau and Dr. Arnold W. Klein

PHOENIX, ARIZ. — The lip that is enhanced with filler should meet definable proportions and yet retain its individuality, Arnold W. Klein, M.D., said at a clinical dermatology conference sponsored by Medicis.

"Lips are about volume but more importantly shape. Any enhancement must be undetectable," said Dr. Klein, who holds a dermatology chair in his name at the University of California, Los Angeles' David Geffen School of Medicine.

Lip augmentation requires fillers to increase facial volume in a subtle and aesthetically pleasing manner, he said. It is not about "simply eradicating lines."

The lower third of the aging face, including the lip, is the area least amenable to plastic surgery. Along with the thinning of both lips, he cited prominent labial mandibular grooves, the ends of the upper lips hanging down, loss of bone support from dentition and from the mandible, and decreased vertical support, he said.

According to Dr. Klein's formulation of the aesthetic lip: "The length of the closed, relaxed mouth should equal the distance between the medial aspect of the irises in the well-proportioned face." In addition, the ratio of the upper lip to the lower lip should be 1:1.6.

When the head is photographed in a postural position with a relaxed mouth, an interpupillary line drawn horizontally across the eyes should be parallel to a horizontal commissural line drawn where the lips meet.

Dr. Klein cited other characteristic facial landmarks including curvature of the dorsum and angulation of the nose. He said the base of the nose should be 18–20 mm above the upper lip, whereas the recommended distance between the lower lip and the chin is 36 mm.

Looking at the postural head position in profile, the physician should make sure both lips touch the "Steiner line," he said.

When seen in profile, the nasolabial angle should be about 84–105 degrees, he continued: "You want a good nasolabial angle."

To illustrate this, he showed a photograph in which one extended line connected the base of the nose to the tip of the nose. A second line from the base of the nose touched the "Glogau-Klein point" at the center edge of the upper lip. The angle is formed where the two lines intersect.

The G-K point describes the "ski slope" shape of the lip in profile as you move from the skin above the lip down onto the pink vermillion. There is always a little upturn, a point of reflection, which becomes lost as one ages, Richard G. Glogau, M.D., told SKIN & ALLERGY NEWS.

The cosmetic implication is that you have to recreate this shape with fillers used in the border of the lip to make the lip young and attractive. Also, if you use too much Botox on the upper lip, the orbicularis muscle flattens and makes an older looking lip. Therefore, it is generally a good idea to combine fillers with the Botox if you are trying to reestablish a youthful looking upper lip, said Dr. Glogau, who is a consultant to Allergan Inc., Medicis, and Inamed Aesthetics.

Dr. Klein cited a study of 100 women which showed that aging lips lose height (Dermatology 2004;208:307–13). He said the most important aspect of lip augmentation involves building buttresses to restore the lost height and the ends of the lips.

"You want flying buttresses to hold up the lips because of the loss of dentition," he said. "You want to restore the ends and build buttresses to support the lip. That's really important."

The choice of filling agent is less important than the physician's skill in using it, according to Dr. Klein, who disclosed ties as a consultant and/or investigator for Allergan Inc., Genzyme, Inamed Aesthetics, Anika Inc., Medicis, SkinMedica, and OrthoNeutrogena.

"It is not what you use. It is how you use it," he said, recommending physicians become really skilled in one or two products rather than plow through what he described as a delicatessen menu of filling agents on the market.

Except for correction of scars, Dr. Klein opposes the use of permanent fillers. He warned that these agents could become increasingly visible or create an unnatural appearance as facial contours change over time. "For aesthetic indications I believe permanent fillers are a formula for disaster," he said.

The Glogau-Klein point shows dimensions of the aesthetic lip. Courtesy Dr. Richard G. Glogau and Dr. Arnold W. Klein

PHOENIX, ARIZ. — The lip that is enhanced with filler should meet definable proportions and yet retain its individuality, Arnold W. Klein, M.D., said at a clinical dermatology conference sponsored by Medicis.

"Lips are about volume but more importantly shape. Any enhancement must be undetectable," said Dr. Klein, who holds a dermatology chair in his name at the University of California, Los Angeles' David Geffen School of Medicine.

Lip augmentation requires fillers to increase facial volume in a subtle and aesthetically pleasing manner, he said. It is not about "simply eradicating lines."

The lower third of the aging face, including the lip, is the area least amenable to plastic surgery. Along with the thinning of both lips, he cited prominent labial mandibular grooves, the ends of the upper lips hanging down, loss of bone support from dentition and from the mandible, and decreased vertical support, he said.

According to Dr. Klein's formulation of the aesthetic lip: "The length of the closed, relaxed mouth should equal the distance between the medial aspect of the irises in the well-proportioned face." In addition, the ratio of the upper lip to the lower lip should be 1:1.6.

When the head is photographed in a postural position with a relaxed mouth, an interpupillary line drawn horizontally across the eyes should be parallel to a horizontal commissural line drawn where the lips meet.

Dr. Klein cited other characteristic facial landmarks including curvature of the dorsum and angulation of the nose. He said the base of the nose should be 18–20 mm above the upper lip, whereas the recommended distance between the lower lip and the chin is 36 mm.

Looking at the postural head position in profile, the physician should make sure both lips touch the "Steiner line," he said.

When seen in profile, the nasolabial angle should be about 84–105 degrees, he continued: "You want a good nasolabial angle."

To illustrate this, he showed a photograph in which one extended line connected the base of the nose to the tip of the nose. A second line from the base of the nose touched the "Glogau-Klein point" at the center edge of the upper lip. The angle is formed where the two lines intersect.

The G-K point describes the "ski slope" shape of the lip in profile as you move from the skin above the lip down onto the pink vermillion. There is always a little upturn, a point of reflection, which becomes lost as one ages, Richard G. Glogau, M.D., told SKIN & ALLERGY NEWS.

The cosmetic implication is that you have to recreate this shape with fillers used in the border of the lip to make the lip young and attractive. Also, if you use too much Botox on the upper lip, the orbicularis muscle flattens and makes an older looking lip. Therefore, it is generally a good idea to combine fillers with the Botox if you are trying to reestablish a youthful looking upper lip, said Dr. Glogau, who is a consultant to Allergan Inc., Medicis, and Inamed Aesthetics.

Dr. Klein cited a study of 100 women which showed that aging lips lose height (Dermatology 2004;208:307–13). He said the most important aspect of lip augmentation involves building buttresses to restore the lost height and the ends of the lips.

"You want flying buttresses to hold up the lips because of the loss of dentition," he said. "You want to restore the ends and build buttresses to support the lip. That's really important."

The choice of filling agent is less important than the physician's skill in using it, according to Dr. Klein, who disclosed ties as a consultant and/or investigator for Allergan Inc., Genzyme, Inamed Aesthetics, Anika Inc., Medicis, SkinMedica, and OrthoNeutrogena.

"It is not what you use. It is how you use it," he said, recommending physicians become really skilled in one or two products rather than plow through what he described as a delicatessen menu of filling agents on the market.

Except for correction of scars, Dr. Klein opposes the use of permanent fillers. He warned that these agents could become increasingly visible or create an unnatural appearance as facial contours change over time. "For aesthetic indications I believe permanent fillers are a formula for disaster," he said.

The Glogau-Klein point shows dimensions of the aesthetic lip. Courtesy Dr. Richard G. Glogau and Dr. Arnold W. Klein

ORLANDO, FLA. — Breast cancer survivors on a low-fat diet had their rate of recurrence reduced by 24% in what may be the first phase III trial to show that a lifestyle change can protect cancer patients from relapse.

In a study with a median of 5 years of follow-up, investigator Rowan T. Chlebowski, M.D., determined the disease had recurred in 12.4% of postmenopausal women on a standard diet but only 9.8% of those on the low-fat regimen.

The protective effect was stronger in women who had estrogen receptor-negative tumors, he reported at the annual meeting of the American Society of Clinical Oncology.

Although patients with such tumors have an elevated risk of relapse, a low-fat diet reduced their risk of recurrence by 42%.

For women who had estrogen receptor-positive cancers, the benefit was a 15% drop in recurrence risk.

“Many physicians would say, how [could] a lifestyle intervention work at all?” Dr. Chlebowski, an oncologist at the Los Angeles Biomedical Research Institute in Torrance, Calif. acknowledged during a press briefing. “It seems unlikely just talking to a dietitian for eight visits [would] change anything.”

During a plenary session discussion of the findings, Eric T. Winer, M.D., called the results “tantalizing,” noting that “the magnitude of effects are similar to many widely accepted interventions.”

Begun in 1994 and stopped because the investigators ran out of funds, the Women's Intervention Nutrition Study (WINS) randomized women at 37 cancer centers within 365 days of surgery for early-stage breast cancer.

The women had an average age of 52 years, with a range of 48 to 79 years. Many also received radiation and adjuvant chemotherapy according to standard protocols.

A total of 975 postmenopausal women were assigned to the low-fat arm, with a goal of reducing fat intake to 15% of calories; they cut their average intake to 33.3 g of fat daily. These women attended eight biweekly nutrition counseling sessions, met with a nutritionist every 3 months, and had monthly group meetings. The program taught them to swap low-fat foods for high-fat foods (for example, eating cereal instead of baked goods), reduce intake of oils and margarines, and eat smaller portions of red meat.

The 1,462 women in the control group consumed an average of 51.3 g of fat per day on their standard diets; they had “dietitian contact” every 3 months, but no additional dietary intervention.

The goal of the low-fat diet was fat reduction, not weight loss, Dr. Chlebowski stressed.

Nonetheless, the women lost a statistically significant 4 pounds on average that may have confounded the results by contributing to the treatment effect.

“The weight loss is remarkable, as women with breast cancer tend to gain weight,” said Dr. Winer of Dana-Farber Cancer Institute in Boston. “Weight gain is common as individuals age.”

He cautioned that the study does not establish that a low-fat diet will protect breast cancer survivors and is, therefore, insufficient to recommend that postmenopausal women with breast cancer use dietary fat reduction to reduce the risk of recurrence.

Dr. Winer called for more research into dietary intervention, noting that the preliminary evidence suggests that a low-fat diet and/or weight loss might, indeed, lower the risk of recurrence.

Dr. Chlebowski said the investigators will continue to follow the patients. The effects would persist for women committed to making a dietary change, he predicted. “It is a sustainable intervention because you are eating different foods rather than trying to lose weight.”

In a statement issued by the American Cancer Society, deputy chief medical officer Len Lichtenfeld, M.D., said comparable findings would be cause for excitement if the trial had been a preventive chemotherapy study.

More trials are needed to determine whether large numbers of women can make and maintain such large dietary changes, he added.

“For now, a postmenopausal woman who has been diagnosed with breast cancer that is estrogen receptor negative should consider adopting a low-fat diet after speaking with her physician,” Dr. Lichtenfeld said. “Until this study has been confirmed by others, we can't say with absolute certainty that this will be beneficial for her breast cancer,” he said.

ORLANDO, FLA. — Breast cancer survivors on a low-fat diet had their rate of recurrence reduced by 24% in what may be the first phase III trial to show that a lifestyle change can protect cancer patients from relapse.

In a study with a median of 5 years of follow-up, investigator Rowan T. Chlebowski, M.D., determined the disease had recurred in 12.4% of postmenopausal women on a standard diet but only 9.8% of those on the low-fat regimen.

The protective effect was stronger in women who had estrogen receptor-negative tumors, he reported at the annual meeting of the American Society of Clinical Oncology.

Although patients with such tumors have an elevated risk of relapse, a low-fat diet reduced their risk of recurrence by 42%.

For women who had estrogen receptor-positive cancers, the benefit was a 15% drop in recurrence risk.

“Many physicians would say, how [could] a lifestyle intervention work at all?” Dr. Chlebowski, an oncologist at the Los Angeles Biomedical Research Institute in Torrance, Calif. acknowledged during a press briefing. “It seems unlikely just talking to a dietitian for eight visits [would] change anything.”

During a plenary session discussion of the findings, Eric T. Winer, M.D., called the results “tantalizing,” noting that “the magnitude of effects are similar to many widely accepted interventions.”

Begun in 1994 and stopped because the investigators ran out of funds, the Women's Intervention Nutrition Study (WINS) randomized women at 37 cancer centers within 365 days of surgery for early-stage breast cancer.

The women had an average age of 52 years, with a range of 48 to 79 years. Many also received radiation and adjuvant chemotherapy according to standard protocols.

A total of 975 postmenopausal women were assigned to the low-fat arm, with a goal of reducing fat intake to 15% of calories; they cut their average intake to 33.3 g of fat daily. These women attended eight biweekly nutrition counseling sessions, met with a nutritionist every 3 months, and had monthly group meetings. The program taught them to swap low-fat foods for high-fat foods (for example, eating cereal instead of baked goods), reduce intake of oils and margarines, and eat smaller portions of red meat.

The 1,462 women in the control group consumed an average of 51.3 g of fat per day on their standard diets; they had “dietitian contact” every 3 months, but no additional dietary intervention.

The goal of the low-fat diet was fat reduction, not weight loss, Dr. Chlebowski stressed.

Nonetheless, the women lost a statistically significant 4 pounds on average that may have confounded the results by contributing to the treatment effect.

“The weight loss is remarkable, as women with breast cancer tend to gain weight,” said Dr. Winer of Dana-Farber Cancer Institute in Boston. “Weight gain is common as individuals age.”

He cautioned that the study does not establish that a low-fat diet will protect breast cancer survivors and is, therefore, insufficient to recommend that postmenopausal women with breast cancer use dietary fat reduction to reduce the risk of recurrence.

Dr. Winer called for more research into dietary intervention, noting that the preliminary evidence suggests that a low-fat diet and/or weight loss might, indeed, lower the risk of recurrence.

Dr. Chlebowski said the investigators will continue to follow the patients. The effects would persist for women committed to making a dietary change, he predicted. “It is a sustainable intervention because you are eating different foods rather than trying to lose weight.”

In a statement issued by the American Cancer Society, deputy chief medical officer Len Lichtenfeld, M.D., said comparable findings would be cause for excitement if the trial had been a preventive chemotherapy study.

More trials are needed to determine whether large numbers of women can make and maintain such large dietary changes, he added.

“For now, a postmenopausal woman who has been diagnosed with breast cancer that is estrogen receptor negative should consider adopting a low-fat diet after speaking with her physician,” Dr. Lichtenfeld said. “Until this study has been confirmed by others, we can't say with absolute certainty that this will be beneficial for her breast cancer,” he said.

ORLANDO, FLA. — Breast cancer survivors on a low-fat diet had their rate of recurrence reduced by 24% in what may be the first phase III trial to show that a lifestyle change can protect cancer patients from relapse.

In a study with a median of 5 years of follow-up, investigator Rowan T. Chlebowski, M.D., determined the disease had recurred in 12.4% of postmenopausal women on a standard diet but only 9.8% of those on the low-fat regimen.

The protective effect was stronger in women who had estrogen receptor-negative tumors, he reported at the annual meeting of the American Society of Clinical Oncology.

Although patients with such tumors have an elevated risk of relapse, a low-fat diet reduced their risk of recurrence by 42%.

For women who had estrogen receptor-positive cancers, the benefit was a 15% drop in recurrence risk.

“Many physicians would say, how [could] a lifestyle intervention work at all?” Dr. Chlebowski, an oncologist at the Los Angeles Biomedical Research Institute in Torrance, Calif. acknowledged during a press briefing. “It seems unlikely just talking to a dietitian for eight visits [would] change anything.”

During a plenary session discussion of the findings, Eric T. Winer, M.D., called the results “tantalizing,” noting that “the magnitude of effects are similar to many widely accepted interventions.”

Begun in 1994 and stopped because the investigators ran out of funds, the Women's Intervention Nutrition Study (WINS) randomized women at 37 cancer centers within 365 days of surgery for early-stage breast cancer.

The women had an average age of 52 years, with a range of 48 to 79 years. Many also received radiation and adjuvant chemotherapy according to standard protocols.

A total of 975 postmenopausal women were assigned to the low-fat arm, with a goal of reducing fat intake to 15% of calories; they cut their average intake to 33.3 g of fat daily. These women attended eight biweekly nutrition counseling sessions, met with a nutritionist every 3 months, and had monthly group meetings. The program taught them to swap low-fat foods for high-fat foods (for example, eating cereal instead of baked goods), reduce intake of oils and margarines, and eat smaller portions of red meat.

The 1,462 women in the control group consumed an average of 51.3 g of fat per day on their standard diets; they had “dietitian contact” every 3 months, but no additional dietary intervention.

The goal of the low-fat diet was fat reduction, not weight loss, Dr. Chlebowski stressed.

Nonetheless, the women lost a statistically significant 4 pounds on average that may have confounded the results by contributing to the treatment effect.

“The weight loss is remarkable, as women with breast cancer tend to gain weight,” said Dr. Winer of Dana-Farber Cancer Institute in Boston. “Weight gain is common as individuals age.”

He cautioned that the study does not establish that a low-fat diet will protect breast cancer survivors and is, therefore, insufficient to recommend that postmenopausal women with breast cancer use dietary fat reduction to reduce the risk of recurrence.

Dr. Winer called for more research into dietary intervention, noting that the preliminary evidence suggests that a low-fat diet and/or weight loss might, indeed, lower the risk of recurrence.

Dr. Chlebowski said the investigators will continue to follow the patients. The effects would persist for women committed to making a dietary change, he predicted. “It is a sustainable intervention because you are eating different foods rather than trying to lose weight.”

In a statement issued by the American Cancer Society, deputy chief medical officer Len Lichtenfeld, M.D., said comparable findings would be cause for excitement if the trial had been a preventive chemotherapy study.

More trials are needed to determine whether large numbers of women can make and maintain such large dietary changes, he added.

“For now, a postmenopausal woman who has been diagnosed with breast cancer that is estrogen receptor negative should consider adopting a low-fat diet after speaking with her physician,” Dr. Lichtenfeld said. “Until this study has been confirmed by others, we can't say with absolute certainty that this will be beneficial for her breast cancer,” he said.

LOS ANGELES — More than a third of the women trying to become pregnant and about half the would-be fathers consumed low levels of vitamin C or vitamin E when they entered a large, randomized clinical trial comparing infertility regimens.

Based on pooled data for both partners, 79% of couples trying to conceive in the Fast Track and Standard Treatment Trial (FASTT) consumed less than the estimated average requirement (EAR) for at least one of these antioxidant vitamins from the food they ate.

The EAR is defined as the daily intake estimated to meet the requirement in half of healthy individuals in each age and gender category.

For example, for pregnant women ages 19–30, the EARs would be 70 mg/day of vitamin C and 12 mg/day of vitamin E.

Even after the researchers factored in dietary supplements, 22% of couples who participated in the study still fell below recommended levels at baseline.

“These are people who wanted to do everything possible to get pregnant, and, even if they were taking supplements, there were couples with both [partners] low in C or E,” study investigator Marlene B. Goldman, Sc.D., said during the annual meeting of the Society for Gynecologic Investigation.

The couples' self-reported baseline intake levels probably are an overestimate of actual intake.

She added: “If anything, we would expect them to overreport.”

Dr. Goldman of Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, presented the nutritional analysis in the first report of data from the study, which was funded by the National Institute of Child Health and Human Development.

Between September 2001 and May 2003, the trial enrolled 250 couples with unexplained infertility, mild male factor, or mild endometriosis.

All of the women who participated in the study had been unable to conceive for at least 12 months; none of the women had undergone prior infertility treatment.

The women were aged 21–39 years with normal ovarian reserve.

No results have been reported yet for the main outcome measures comparing an accelerated regimen of clomiphene and intrauterine insemination followed by in vitro fertilization to a standard regimen of clomiphene and intrauterine insemination followed by gonadotropin and intrauterine insemination followed by in vitro fertilization.

The investigators said recent animal research suggests antioxidants play a role in ovulation and fertilization, but human data in this area were limited. “Our hypothesis is that oxidative stress might negatively impact the ability to establish pregnancy,” Dr. Goldman said of the decision to compare the study population's nutritional intake with national recommendations.

Patients completed the 1998 Block food questionnaire from Block Dietary Data Systems in Berkeley, Calif., upon enrollment. The validated survey included 110 food items, with analysis for 36 macro- and micronutrients.

Data were available for a total of 241 women (mean age 33) and 229 men (mean age 34).

Less than 7% of women and 12% of men were smokers. Most women, 83%, but less than half the men, 41%, used supplements.

Most couples, 52%, did not meet the standard recommendation of five servings per day of fruit and vegetables. A total of 68% of women and 74% of men consumed fewer than five servings per day: The average was 4.1 servings for women and 4 servings for men.

For the antioxidant analysis, the investigators matched reported intake to recommended daily intake values for each person's age and gender.

When diet alone was analyzed, 15% of couples consumed too little vitamin C, and 78% of couples were low on vitamin E intake. Among those who took a dietary supplement, the percentage fell to 4% consuming too little vitamin C, but 21% still were not getting enough vitamin E.

Based on diet alone, 94% of women were low on vitamin C or E. Even with a supplement, 34% did not meet the recommendation for at least one of the antioxidants.

Among the men, 85% did not get enough vitamins C or E from their diets. More than half of the men who were taking a supplement, 53%, still did not meet the daily recommendations for vitamins C or E.

The investigators announced plans to evaluate the relationship of antioxidant status and other nutritional factors to time to pregnancy and pregnancy outcomes in the trial population.

LOS ANGELES — More than a third of the women trying to become pregnant and about half the would-be fathers consumed low levels of vitamin C or vitamin E when they entered a large, randomized clinical trial comparing infertility regimens.

Based on pooled data for both partners, 79% of couples trying to conceive in the Fast Track and Standard Treatment Trial (FASTT) consumed less than the estimated average requirement (EAR) for at least one of these antioxidant vitamins from the food they ate.

The EAR is defined as the daily intake estimated to meet the requirement in half of healthy individuals in each age and gender category.

For example, for pregnant women ages 19–30, the EARs would be 70 mg/day of vitamin C and 12 mg/day of vitamin E.

Even after the researchers factored in dietary supplements, 22% of couples who participated in the study still fell below recommended levels at baseline.

“These are people who wanted to do everything possible to get pregnant, and, even if they were taking supplements, there were couples with both [partners] low in C or E,” study investigator Marlene B. Goldman, Sc.D., said during the annual meeting of the Society for Gynecologic Investigation.

The couples' self-reported baseline intake levels probably are an overestimate of actual intake.

She added: “If anything, we would expect them to overreport.”

Dr. Goldman of Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, presented the nutritional analysis in the first report of data from the study, which was funded by the National Institute of Child Health and Human Development.

Between September 2001 and May 2003, the trial enrolled 250 couples with unexplained infertility, mild male factor, or mild endometriosis.

All of the women who participated in the study had been unable to conceive for at least 12 months; none of the women had undergone prior infertility treatment.

The women were aged 21–39 years with normal ovarian reserve.

No results have been reported yet for the main outcome measures comparing an accelerated regimen of clomiphene and intrauterine insemination followed by in vitro fertilization to a standard regimen of clomiphene and intrauterine insemination followed by gonadotropin and intrauterine insemination followed by in vitro fertilization.

The investigators said recent animal research suggests antioxidants play a role in ovulation and fertilization, but human data in this area were limited. “Our hypothesis is that oxidative stress might negatively impact the ability to establish pregnancy,” Dr. Goldman said of the decision to compare the study population's nutritional intake with national recommendations.

Patients completed the 1998 Block food questionnaire from Block Dietary Data Systems in Berkeley, Calif., upon enrollment. The validated survey included 110 food items, with analysis for 36 macro- and micronutrients.

Data were available for a total of 241 women (mean age 33) and 229 men (mean age 34).

Less than 7% of women and 12% of men were smokers. Most women, 83%, but less than half the men, 41%, used supplements.

Most couples, 52%, did not meet the standard recommendation of five servings per day of fruit and vegetables. A total of 68% of women and 74% of men consumed fewer than five servings per day: The average was 4.1 servings for women and 4 servings for men.

For the antioxidant analysis, the investigators matched reported intake to recommended daily intake values for each person's age and gender.

When diet alone was analyzed, 15% of couples consumed too little vitamin C, and 78% of couples were low on vitamin E intake. Among those who took a dietary supplement, the percentage fell to 4% consuming too little vitamin C, but 21% still were not getting enough vitamin E.

Based on diet alone, 94% of women were low on vitamin C or E. Even with a supplement, 34% did not meet the recommendation for at least one of the antioxidants.

Among the men, 85% did not get enough vitamins C or E from their diets. More than half of the men who were taking a supplement, 53%, still did not meet the daily recommendations for vitamins C or E.

The investigators announced plans to evaluate the relationship of antioxidant status and other nutritional factors to time to pregnancy and pregnancy outcomes in the trial population.

LOS ANGELES — More than a third of the women trying to become pregnant and about half the would-be fathers consumed low levels of vitamin C or vitamin E when they entered a large, randomized clinical trial comparing infertility regimens.

Based on pooled data for both partners, 79% of couples trying to conceive in the Fast Track and Standard Treatment Trial (FASTT) consumed less than the estimated average requirement (EAR) for at least one of these antioxidant vitamins from the food they ate.

The EAR is defined as the daily intake estimated to meet the requirement in half of healthy individuals in each age and gender category.

For example, for pregnant women ages 19–30, the EARs would be 70 mg/day of vitamin C and 12 mg/day of vitamin E.

Even after the researchers factored in dietary supplements, 22% of couples who participated in the study still fell below recommended levels at baseline.

“These are people who wanted to do everything possible to get pregnant, and, even if they were taking supplements, there were couples with both [partners] low in C or E,” study investigator Marlene B. Goldman, Sc.D., said during the annual meeting of the Society for Gynecologic Investigation.

The couples' self-reported baseline intake levels probably are an overestimate of actual intake.

She added: “If anything, we would expect them to overreport.”

Dr. Goldman of Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston, presented the nutritional analysis in the first report of data from the study, which was funded by the National Institute of Child Health and Human Development.

Between September 2001 and May 2003, the trial enrolled 250 couples with unexplained infertility, mild male factor, or mild endometriosis.

All of the women who participated in the study had been unable to conceive for at least 12 months; none of the women had undergone prior infertility treatment.

The women were aged 21–39 years with normal ovarian reserve.

No results have been reported yet for the main outcome measures comparing an accelerated regimen of clomiphene and intrauterine insemination followed by in vitro fertilization to a standard regimen of clomiphene and intrauterine insemination followed by gonadotropin and intrauterine insemination followed by in vitro fertilization.

The investigators said recent animal research suggests antioxidants play a role in ovulation and fertilization, but human data in this area were limited. “Our hypothesis is that oxidative stress might negatively impact the ability to establish pregnancy,” Dr. Goldman said of the decision to compare the study population's nutritional intake with national recommendations.

Patients completed the 1998 Block food questionnaire from Block Dietary Data Systems in Berkeley, Calif., upon enrollment. The validated survey included 110 food items, with analysis for 36 macro- and micronutrients.

Data were available for a total of 241 women (mean age 33) and 229 men (mean age 34).

Less than 7% of women and 12% of men were smokers. Most women, 83%, but less than half the men, 41%, used supplements.

Most couples, 52%, did not meet the standard recommendation of five servings per day of fruit and vegetables. A total of 68% of women and 74% of men consumed fewer than five servings per day: The average was 4.1 servings for women and 4 servings for men.

For the antioxidant analysis, the investigators matched reported intake to recommended daily intake values for each person's age and gender.

When diet alone was analyzed, 15% of couples consumed too little vitamin C, and 78% of couples were low on vitamin E intake. Among those who took a dietary supplement, the percentage fell to 4% consuming too little vitamin C, but 21% still were not getting enough vitamin E.

Based on diet alone, 94% of women were low on vitamin C or E. Even with a supplement, 34% did not meet the recommendation for at least one of the antioxidants.

Among the men, 85% did not get enough vitamins C or E from their diets. More than half of the men who were taking a supplement, 53%, still did not meet the daily recommendations for vitamins C or E.

The investigators announced plans to evaluate the relationship of antioxidant status and other nutritional factors to time to pregnancy and pregnancy outcomes in the trial population.

LOS ANGELES — Pregnancies complicated by type 1 or type 2 diabetes mellitus can have good outcomes with new strategies for glucose control, Steven G. Gabbe, M.D., said at the annual meeting of the Society for Gynecologic Investigation.

At less than 5%, the perinatal mortality of children whose mothers have diabetes is comparable with the rate in children of women without diabetes, according to Dr. Gabbe, dean of Vanderbilt University School of Medicine in Nashville, Tenn.

Nonetheless, preventing congenital malformations and overly large babies remains a challenge. “We have to develop individualized programs of insulin for our patients,” he said, offering strategies for patient education and self-management.

Glucose control goals change with pregnancy, said Dr. Gabbe. Physicians should counsel diabetic women before conception to bring their glycosylated hemoglobin (HbA_1c) levels to no more than 1% above the normal range. Targeted plasma glucose levels should be 80–110 mg/dL before meals and less than 155 mg/dL after meals.

During pregnancy, target plasma glucose levels should be 60–90 mg/dL before breakfast; 60–105 mg/dL before lunch, supper, or a bedtime snack; less than 120 mg/dL 2 hours after meals; and above 60 mg/dL between 2 a.m. and 6 a.m. The mean capillary glucose level should be maintained below 100 mg/dL.

To help patients use HbA_1c levels to approximate mean glucose levels, he suggested teaching them “the rule of eights”: An HbA_1c of 8% equals 180 mg/dL, and each 1% change equals ±30 mg/dL.

Pregnant patients need to understand that there is a “lag time” between an injection of insulin and a meal (N. Engl. J. Med. 2005;352:174–83), he continued. Physicians should also warn them against “insulin stacking” in which a correction dose of insulin is given before the prior dose of prandial insulin has reached its peak effect (JAMA 2003;289:2254–64).

Insulin stacking leads to hypoglycemia, he warned. “You have to remember and remind patients about overcorrecting with too much insulin too soon before the insulin they have taken has played out.”

Dr. Gabbe said insulin levels increase in pregnancy, but changes can vary for each woman. To help with the adjustment, he advised teaching the patient that:

▸ One unit of short-acting insulin will lower her blood glucose level by approximately 30 mg/dL.

▸ Ten grams of carbohydrate will elevate her blood glucose by about 30 mg/dL.

▸ One unit of short-acting insulin will cover approximately 10 g of carbohydrates.

He recommended the short-acting insulins lispro and aspart for pregnant patients; these can be injected or used with an insulin pump. He said there are concerns but not much experience with the long-acting insulin glargine in pregnancy.

Insulin pumps offer many advantages. Along with eliminating the need for multiple injections, they provide a continuous basal rate, which reduces the risk of mean glucose excursions and hypoglycemia. They also allow a more flexible lifestyle.

But the pumps also have disadvantages. They require excellent compliance, intensive glucose monitoring, and can produce hypo- or hyperglycemia if mechanical problems occur. Pump failure increases the risk of ketoacidosis, and there is the potential for infection at the insertion site. It also “costs $140 more per month to use a pump vs. multiple injections,” he said.

Whatever method is used, Dr. Gabbe said diet is critical as well. Patients should have three meals and three snacks each day.

Another concern is hypoglycemia unawareness, which could be exacerbated by intensive insulin therapy during pregnancy. Determine if the patient has hypoglycemia unawareness; review and adjust her diet, insulin, and exercise; and teach family members to treat hypoglycemia, Dr. Gabbe said.

“Does all of this really make a difference?” he asked rhetorically. “Yes, it does—in having a baby that grows normally and behaves normally in the nursery.”

LOS ANGELES — Pregnancies complicated by type 1 or type 2 diabetes mellitus can have good outcomes with new strategies for glucose control, Steven G. Gabbe, M.D., said at the annual meeting of the Society for Gynecologic Investigation.

At less than 5%, the perinatal mortality of children whose mothers have diabetes is comparable with the rate in children of women without diabetes, according to Dr. Gabbe, dean of Vanderbilt University School of Medicine in Nashville, Tenn.

Nonetheless, preventing congenital malformations and overly large babies remains a challenge. “We have to develop individualized programs of insulin for our patients,” he said, offering strategies for patient education and self-management.

Glucose control goals change with pregnancy, said Dr. Gabbe. Physicians should counsel diabetic women before conception to bring their glycosylated hemoglobin (HbA_1c) levels to no more than 1% above the normal range. Targeted plasma glucose levels should be 80–110 mg/dL before meals and less than 155 mg/dL after meals.

During pregnancy, target plasma glucose levels should be 60–90 mg/dL before breakfast; 60–105 mg/dL before lunch, supper, or a bedtime snack; less than 120 mg/dL 2 hours after meals; and above 60 mg/dL between 2 a.m. and 6 a.m. The mean capillary glucose level should be maintained below 100 mg/dL.

To help patients use HbA_1c levels to approximate mean glucose levels, he suggested teaching them “the rule of eights”: An HbA_1c of 8% equals 180 mg/dL, and each 1% change equals ±30 mg/dL.

Pregnant patients need to understand that there is a “lag time” between an injection of insulin and a meal (N. Engl. J. Med. 2005;352:174–83), he continued. Physicians should also warn them against “insulin stacking” in which a correction dose of insulin is given before the prior dose of prandial insulin has reached its peak effect (JAMA 2003;289:2254–64).

Insulin stacking leads to hypoglycemia, he warned. “You have to remember and remind patients about overcorrecting with too much insulin too soon before the insulin they have taken has played out.”

Dr. Gabbe said insulin levels increase in pregnancy, but changes can vary for each woman. To help with the adjustment, he advised teaching the patient that:

▸ One unit of short-acting insulin will lower her blood glucose level by approximately 30 mg/dL.

▸ Ten grams of carbohydrate will elevate her blood glucose by about 30 mg/dL.

▸ One unit of short-acting insulin will cover approximately 10 g of carbohydrates.

He recommended the short-acting insulins lispro and aspart for pregnant patients; these can be injected or used with an insulin pump. He said there are concerns but not much experience with the long-acting insulin glargine in pregnancy.

Insulin pumps offer many advantages. Along with eliminating the need for multiple injections, they provide a continuous basal rate, which reduces the risk of mean glucose excursions and hypoglycemia. They also allow a more flexible lifestyle.

But the pumps also have disadvantages. They require excellent compliance, intensive glucose monitoring, and can produce hypo- or hyperglycemia if mechanical problems occur. Pump failure increases the risk of ketoacidosis, and there is the potential for infection at the insertion site. It also “costs $140 more per month to use a pump vs. multiple injections,” he said.

Whatever method is used, Dr. Gabbe said diet is critical as well. Patients should have three meals and three snacks each day.

Another concern is hypoglycemia unawareness, which could be exacerbated by intensive insulin therapy during pregnancy. Determine if the patient has hypoglycemia unawareness; review and adjust her diet, insulin, and exercise; and teach family members to treat hypoglycemia, Dr. Gabbe said.

“Does all of this really make a difference?” he asked rhetorically. “Yes, it does—in having a baby that grows normally and behaves normally in the nursery.”

LOS ANGELES — Pregnancies complicated by type 1 or type 2 diabetes mellitus can have good outcomes with new strategies for glucose control, Steven G. Gabbe, M.D., said at the annual meeting of the Society for Gynecologic Investigation.

At less than 5%, the perinatal mortality of children whose mothers have diabetes is comparable with the rate in children of women without diabetes, according to Dr. Gabbe, dean of Vanderbilt University School of Medicine in Nashville, Tenn.

Nonetheless, preventing congenital malformations and overly large babies remains a challenge. “We have to develop individualized programs of insulin for our patients,” he said, offering strategies for patient education and self-management.

Glucose control goals change with pregnancy, said Dr. Gabbe. Physicians should counsel diabetic women before conception to bring their glycosylated hemoglobin (HbA_1c) levels to no more than 1% above the normal range. Targeted plasma glucose levels should be 80–110 mg/dL before meals and less than 155 mg/dL after meals.

During pregnancy, target plasma glucose levels should be 60–90 mg/dL before breakfast; 60–105 mg/dL before lunch, supper, or a bedtime snack; less than 120 mg/dL 2 hours after meals; and above 60 mg/dL between 2 a.m. and 6 a.m. The mean capillary glucose level should be maintained below 100 mg/dL.

To help patients use HbA_1c levels to approximate mean glucose levels, he suggested teaching them “the rule of eights”: An HbA_1c of 8% equals 180 mg/dL, and each 1% change equals ±30 mg/dL.

Pregnant patients need to understand that there is a “lag time” between an injection of insulin and a meal (N. Engl. J. Med. 2005;352:174–83), he continued. Physicians should also warn them against “insulin stacking” in which a correction dose of insulin is given before the prior dose of prandial insulin has reached its peak effect (JAMA 2003;289:2254–64).

Insulin stacking leads to hypoglycemia, he warned. “You have to remember and remind patients about overcorrecting with too much insulin too soon before the insulin they have taken has played out.”

Dr. Gabbe said insulin levels increase in pregnancy, but changes can vary for each woman. To help with the adjustment, he advised teaching the patient that:

▸ One unit of short-acting insulin will lower her blood glucose level by approximately 30 mg/dL.

▸ Ten grams of carbohydrate will elevate her blood glucose by about 30 mg/dL.

▸ One unit of short-acting insulin will cover approximately 10 g of carbohydrates.

He recommended the short-acting insulins lispro and aspart for pregnant patients; these can be injected or used with an insulin pump. He said there are concerns but not much experience with the long-acting insulin glargine in pregnancy.

Insulin pumps offer many advantages. Along with eliminating the need for multiple injections, they provide a continuous basal rate, which reduces the risk of mean glucose excursions and hypoglycemia. They also allow a more flexible lifestyle.

But the pumps also have disadvantages. They require excellent compliance, intensive glucose monitoring, and can produce hypo- or hyperglycemia if mechanical problems occur. Pump failure increases the risk of ketoacidosis, and there is the potential for infection at the insertion site. It also “costs $140 more per month to use a pump vs. multiple injections,” he said.

Whatever method is used, Dr. Gabbe said diet is critical as well. Patients should have three meals and three snacks each day.

Another concern is hypoglycemia unawareness, which could be exacerbated by intensive insulin therapy during pregnancy. Determine if the patient has hypoglycemia unawareness; review and adjust her diet, insulin, and exercise; and teach family members to treat hypoglycemia, Dr. Gabbe said.

“Does all of this really make a difference?” he asked rhetorically. “Yes, it does—in having a baby that grows normally and behaves normally in the nursery.”

LOS ANGELES — Scientists have developed a noninvasive “genetic Pap” test to screen for Down syndrome and other chromosomal abnormalities early in pregnancy.

The test analyzes trophoblast cells shed by the fetus and scraped from the cervix, investigator Moshe D. Fejgin, M.D., reported in an oral presentation at the annual meeting of the Society for Gynecologic Investigation.

Researchers found fetal cells in about 87% of nearly 500 samples from two studies. The test identified two cases of trisomy 21 and one case each of Turner's syndrome and Klinefelter's syndrome in 110 pregnancies, according to Dr. Fejgin of the Meir Medical Center in Kfar Saba, Israel.

Gender predictions were correct in 92% of samples, he said, with accuracy ranging from 89% in samples from women planning to complete their pregnancies and 94% from a group that chose termination. Dr. Fejgin described the test as 100% accurate in determining male gender.

“When you are running 80%–90% accuracy, it can be used as a diagnostic,” Dr. Fejgin said.

He and his coinvestigators concluded that the “genetic Pap” has the potential to replace other noninvasive screening techniques for Down syndrome.

Their announced goal is to find an alternative to invasive procedures such as amniocentesis and chorionic villi sampling, which can be risky as well as costly.

The concept is not entirely new. Scientists have long attempted to isolate fetal cells from maternal blood for this purpose without success, according to Dr. Fejgin.

Fetal cells are shed into the cervix between 5 and 12 weeks of gestation, Dr. Fejgin said, describing the time frame as a window of opportunity for the “genetic Pap.”

After the cells are obtained with a cytobrush, the screening process includes immunohistochemistry and fluorescence in situ hybridization (FISH) analysis for gender and for chromosomal abnormalities.

The investigators have formed a company to commercialize the test, Dr. Fejgin added during an interview.

He said they plan to start clinical trials in Europe and the United States and plan to submit the test to the Food and Drug Administration for approval.

LOS ANGELES — Scientists have developed a noninvasive “genetic Pap” test to screen for Down syndrome and other chromosomal abnormalities early in pregnancy.

The test analyzes trophoblast cells shed by the fetus and scraped from the cervix, investigator Moshe D. Fejgin, M.D., reported in an oral presentation at the annual meeting of the Society for Gynecologic Investigation.

Researchers found fetal cells in about 87% of nearly 500 samples from two studies. The test identified two cases of trisomy 21 and one case each of Turner's syndrome and Klinefelter's syndrome in 110 pregnancies, according to Dr. Fejgin of the Meir Medical Center in Kfar Saba, Israel.

Gender predictions were correct in 92% of samples, he said, with accuracy ranging from 89% in samples from women planning to complete their pregnancies and 94% from a group that chose termination. Dr. Fejgin described the test as 100% accurate in determining male gender.

“When you are running 80%–90% accuracy, it can be used as a diagnostic,” Dr. Fejgin said.

He and his coinvestigators concluded that the “genetic Pap” has the potential to replace other noninvasive screening techniques for Down syndrome.

Their announced goal is to find an alternative to invasive procedures such as amniocentesis and chorionic villi sampling, which can be risky as well as costly.

The concept is not entirely new. Scientists have long attempted to isolate fetal cells from maternal blood for this purpose without success, according to Dr. Fejgin.

Fetal cells are shed into the cervix between 5 and 12 weeks of gestation, Dr. Fejgin said, describing the time frame as a window of opportunity for the “genetic Pap.”

After the cells are obtained with a cytobrush, the screening process includes immunohistochemistry and fluorescence in situ hybridization (FISH) analysis for gender and for chromosomal abnormalities.

The investigators have formed a company to commercialize the test, Dr. Fejgin added during an interview.

He said they plan to start clinical trials in Europe and the United States and plan to submit the test to the Food and Drug Administration for approval.

LOS ANGELES — Scientists have developed a noninvasive “genetic Pap” test to screen for Down syndrome and other chromosomal abnormalities early in pregnancy.

The test analyzes trophoblast cells shed by the fetus and scraped from the cervix, investigator Moshe D. Fejgin, M.D., reported in an oral presentation at the annual meeting of the Society for Gynecologic Investigation.

Researchers found fetal cells in about 87% of nearly 500 samples from two studies. The test identified two cases of trisomy 21 and one case each of Turner's syndrome and Klinefelter's syndrome in 110 pregnancies, according to Dr. Fejgin of the Meir Medical Center in Kfar Saba, Israel.

Gender predictions were correct in 92% of samples, he said, with accuracy ranging from 89% in samples from women planning to complete their pregnancies and 94% from a group that chose termination. Dr. Fejgin described the test as 100% accurate in determining male gender.

“When you are running 80%–90% accuracy, it can be used as a diagnostic,” Dr. Fejgin said.

He and his coinvestigators concluded that the “genetic Pap” has the potential to replace other noninvasive screening techniques for Down syndrome.

Their announced goal is to find an alternative to invasive procedures such as amniocentesis and chorionic villi sampling, which can be risky as well as costly.

The concept is not entirely new. Scientists have long attempted to isolate fetal cells from maternal blood for this purpose without success, according to Dr. Fejgin.

Fetal cells are shed into the cervix between 5 and 12 weeks of gestation, Dr. Fejgin said, describing the time frame as a window of opportunity for the “genetic Pap.”

After the cells are obtained with a cytobrush, the screening process includes immunohistochemistry and fluorescence in situ hybridization (FISH) analysis for gender and for chromosomal abnormalities.

The investigators have formed a company to commercialize the test, Dr. Fejgin added during an interview.

He said they plan to start clinical trials in Europe and the United States and plan to submit the test to the Food and Drug Administration for approval.

LOS ANGELES — A small study adds to the growing body of evidence implicating periodontal disease in poor pregnancy outcomes.

Twelve percent of women with periodontal disease had low-birth-weight babies in a 277-patient observational study. In comparison, only 2% of women with healthy gums had small babies, a statistically significant difference.

The data were presented in poster form at the annual meeting of the Society for Gynecologic Investigation.

The women with periodontal disease also had a higher incidence of preterm births (7% vs. 3%) but Alexis L. Shub, M.D., an investigator in the study, said this difference was not statistically significant. About 15% of women in the study had periodontal disease.

An updated analysis completed just before the meeting also found higher rates of tumor necrosis factor-α in the cord blood of women with periodontal disease, Dr. Shub, an obstetrician at the University of Western Australia in Perth, said in an interview.

These data were not included in the poster presentation, she noted, adding that the findings suggest an ongoing inflammatory process in these women and their fetuses.

John P. Newnham, M.D., who is the study's lead author and director of the Women and Infants Research Foundation at King Edward Memorial Hospital in Perth, said in an interview that he is also working on a large, randomized controlled trial to study this issue. The investigators have begun to divide 1,000 pregnant women with periodontal disease into two cohorts: one given periodontal care during pregnancy and the other afterward. The trial's primary outcomes will be preterm birth, fetal growth, and preeclampsia.

He said the investigators are concerned that heightened awareness of possible harm from periodontal disease could skew outcomes. They suspect screening patients for periodontal disease in the observational study led to better dental care. The preterm birth rates were expected to be about 11%, according to Dr. Newnham, who also plans to monitor pregnancy outcomes and prenatal care in a region-wide medical database.

“The exciting thing is that it is possible that a simple community-based public health intervention could have a profound impact on the need for expensive high-tech hospital resources,” he said.

LOS ANGELES — A small study adds to the growing body of evidence implicating periodontal disease in poor pregnancy outcomes.

Twelve percent of women with periodontal disease had low-birth-weight babies in a 277-patient observational study. In comparison, only 2% of women with healthy gums had small babies, a statistically significant difference.

The data were presented in poster form at the annual meeting of the Society for Gynecologic Investigation.

The women with periodontal disease also had a higher incidence of preterm births (7% vs. 3%) but Alexis L. Shub, M.D., an investigator in the study, said this difference was not statistically significant. About 15% of women in the study had periodontal disease.

An updated analysis completed just before the meeting also found higher rates of tumor necrosis factor-α in the cord blood of women with periodontal disease, Dr. Shub, an obstetrician at the University of Western Australia in Perth, said in an interview.

These data were not included in the poster presentation, she noted, adding that the findings suggest an ongoing inflammatory process in these women and their fetuses.

John P. Newnham, M.D., who is the study's lead author and director of the Women and Infants Research Foundation at King Edward Memorial Hospital in Perth, said in an interview that he is also working on a large, randomized controlled trial to study this issue. The investigators have begun to divide 1,000 pregnant women with periodontal disease into two cohorts: one given periodontal care during pregnancy and the other afterward. The trial's primary outcomes will be preterm birth, fetal growth, and preeclampsia.

He said the investigators are concerned that heightened awareness of possible harm from periodontal disease could skew outcomes. They suspect screening patients for periodontal disease in the observational study led to better dental care. The preterm birth rates were expected to be about 11%, according to Dr. Newnham, who also plans to monitor pregnancy outcomes and prenatal care in a region-wide medical database.

“The exciting thing is that it is possible that a simple community-based public health intervention could have a profound impact on the need for expensive high-tech hospital resources,” he said.

LOS ANGELES — A small study adds to the growing body of evidence implicating periodontal disease in poor pregnancy outcomes.

Twelve percent of women with periodontal disease had low-birth-weight babies in a 277-patient observational study. In comparison, only 2% of women with healthy gums had small babies, a statistically significant difference.

The data were presented in poster form at the annual meeting of the Society for Gynecologic Investigation.

The women with periodontal disease also had a higher incidence of preterm births (7% vs. 3%) but Alexis L. Shub, M.D., an investigator in the study, said this difference was not statistically significant. About 15% of women in the study had periodontal disease.

An updated analysis completed just before the meeting also found higher rates of tumor necrosis factor-α in the cord blood of women with periodontal disease, Dr. Shub, an obstetrician at the University of Western Australia in Perth, said in an interview.

These data were not included in the poster presentation, she noted, adding that the findings suggest an ongoing inflammatory process in these women and their fetuses.

John P. Newnham, M.D., who is the study's lead author and director of the Women and Infants Research Foundation at King Edward Memorial Hospital in Perth, said in an interview that he is also working on a large, randomized controlled trial to study this issue. The investigators have begun to divide 1,000 pregnant women with periodontal disease into two cohorts: one given periodontal care during pregnancy and the other afterward. The trial's primary outcomes will be preterm birth, fetal growth, and preeclampsia.

He said the investigators are concerned that heightened awareness of possible harm from periodontal disease could skew outcomes. They suspect screening patients for periodontal disease in the observational study led to better dental care. The preterm birth rates were expected to be about 11%, according to Dr. Newnham, who also plans to monitor pregnancy outcomes and prenatal care in a region-wide medical database.

“The exciting thing is that it is possible that a simple community-based public health intervention could have a profound impact on the need for expensive high-tech hospital resources,” he said.

LOS ANGELES — Physicians counseling patients after in vitro fertilization can use early β-HCG levels and slopes to predict whether a pregnancy is viable, according to a study presented at the annual meeting of the Society for Gynecologic Investigation.

Researchers in the Center for Reproductive Medicine at New Jersey Medical School, Newark, have identified β-HCG thresholds at 16 and 18 days after oocyte retrieval based on a retrospective chart review of 322 pregnancies by in vitro fertilization.

Investigator Shirley A. Fong, M.D., and her colleagues reported in a poster presentation at the meeting that the new levels were highly significant for distinguishing viable pregnancies from those that did not sustain a fetal heart beat through the first trimester. They also were significantly higher for multiple pregnancies, compared with singleton pregnancies.

“What it puts in my mind is, if their first level is below 100, they are probably not going to have a viable pregnancy outcome. … I know to couch my counseling,” Dr. Fong said in an interview.

The investigators reviewed all IVF pregnancies at the New Jersey center from June 1998 to March 2004. A total of 53 patients did not have a fetal heartbeat at the end of the first trimester. Their mean β-HCG levels were 56 mIU/mL on day 16, and 115 mIU/mL on day 18, with an average slope of 24 mIU/mL.

Levels and slopes were much higher for the remaining 269 women with viable pregnancies with mean levels of 216 mIU/mL on day 16 and 505 mIU/mL on day 18, with an average slope of 140 mIU/mL.

Most of the women, 180, had singleton pregnancies. Their average β-HCG levels were 169 mIU/mL on day 16 and 401 mIU/mL on day 18. The researchers noted that the average slope of 111 mIU/mL was 4.62 times higher than in the pregnancies that were not viable.

For the 89 women who had multiple births, average β-HCG levels were 348 mIU/mL on day 16 and 798 mIU/mL on day 18. Their average slope, 220 mIU/mL, was reported as 9.16 times higher than the slope in patients who did not have a fetal heart beat at the end of the first trimester.

Dr. Fong said the group undertook the study because they did not know how to advise patients with β-HCG levels that are low but not low enough to establish that a pregnancy is not viable.

“Are you enthusiastic? Are you guarded? What sort of tone should you take with your patient when giving levels?” she said. “Often they ask what that means, and we were looking for a point when we should be cautious in advising patients about what their pregnancy outcomes are going to be.”

The investigators noted that β-HCG levels and their rate of rise over 48 hours have been used to manage early pregnancy in the absence of ultrasound. They said the threshold has been a rise of 66% or more over 48 hours to predict a viable pregnancy.

This threshold was based on a 20-patient study with a confidence interval of 85% (Obstet. Gynecol. 1981;58:162–6), according to Dr. Fong.

She and her colleagues have noted that the researchers in that study concluded that about 15% of normal intrauterine pregnancies would appear abnormal by this measure, and that diagnosis actually would be delayed beyond 48 hours in an estimated 13% of ectopic pregnancies.

Dr. Fong emphasized that the new study is specific to in vitro fertilization and more accurate with a confidence interval of 95%. Dr. Fong also cautioned, however, that the averages are not absolutes and that the study does not predict pregnancy outcomes beyond the first trimester.

“We are just reporting a fetal heart,” she said. “People miscarry for reasons other than infertility.”

LOS ANGELES — Physicians counseling patients after in vitro fertilization can use early β-HCG levels and slopes to predict whether a pregnancy is viable, according to a study presented at the annual meeting of the Society for Gynecologic Investigation.

Researchers in the Center for Reproductive Medicine at New Jersey Medical School, Newark, have identified β-HCG thresholds at 16 and 18 days after oocyte retrieval based on a retrospective chart review of 322 pregnancies by in vitro fertilization.

Investigator Shirley A. Fong, M.D., and her colleagues reported in a poster presentation at the meeting that the new levels were highly significant for distinguishing viable pregnancies from those that did not sustain a fetal heart beat through the first trimester. They also were significantly higher for multiple pregnancies, compared with singleton pregnancies.

“What it puts in my mind is, if their first level is below 100, they are probably not going to have a viable pregnancy outcome. … I know to couch my counseling,” Dr. Fong said in an interview.

The investigators reviewed all IVF pregnancies at the New Jersey center from June 1998 to March 2004. A total of 53 patients did not have a fetal heartbeat at the end of the first trimester. Their mean β-HCG levels were 56 mIU/mL on day 16, and 115 mIU/mL on day 18, with an average slope of 24 mIU/mL.

Levels and slopes were much higher for the remaining 269 women with viable pregnancies with mean levels of 216 mIU/mL on day 16 and 505 mIU/mL on day 18, with an average slope of 140 mIU/mL.

Most of the women, 180, had singleton pregnancies. Their average β-HCG levels were 169 mIU/mL on day 16 and 401 mIU/mL on day 18. The researchers noted that the average slope of 111 mIU/mL was 4.62 times higher than in the pregnancies that were not viable.

For the 89 women who had multiple births, average β-HCG levels were 348 mIU/mL on day 16 and 798 mIU/mL on day 18. Their average slope, 220 mIU/mL, was reported as 9.16 times higher than the slope in patients who did not have a fetal heart beat at the end of the first trimester.

Dr. Fong said the group undertook the study because they did not know how to advise patients with β-HCG levels that are low but not low enough to establish that a pregnancy is not viable.

“Are you enthusiastic? Are you guarded? What sort of tone should you take with your patient when giving levels?” she said. “Often they ask what that means, and we were looking for a point when we should be cautious in advising patients about what their pregnancy outcomes are going to be.”

The investigators noted that β-HCG levels and their rate of rise over 48 hours have been used to manage early pregnancy in the absence of ultrasound. They said the threshold has been a rise of 66% or more over 48 hours to predict a viable pregnancy.

This threshold was based on a 20-patient study with a confidence interval of 85% (Obstet. Gynecol. 1981;58:162–6), according to Dr. Fong.

She and her colleagues have noted that the researchers in that study concluded that about 15% of normal intrauterine pregnancies would appear abnormal by this measure, and that diagnosis actually would be delayed beyond 48 hours in an estimated 13% of ectopic pregnancies.

Dr. Fong emphasized that the new study is specific to in vitro fertilization and more accurate with a confidence interval of 95%. Dr. Fong also cautioned, however, that the averages are not absolutes and that the study does not predict pregnancy outcomes beyond the first trimester.

“We are just reporting a fetal heart,” she said. “People miscarry for reasons other than infertility.”

LOS ANGELES — Physicians counseling patients after in vitro fertilization can use early β-HCG levels and slopes to predict whether a pregnancy is viable, according to a study presented at the annual meeting of the Society for Gynecologic Investigation.

Researchers in the Center for Reproductive Medicine at New Jersey Medical School, Newark, have identified β-HCG thresholds at 16 and 18 days after oocyte retrieval based on a retrospective chart review of 322 pregnancies by in vitro fertilization.

Investigator Shirley A. Fong, M.D., and her colleagues reported in a poster presentation at the meeting that the new levels were highly significant for distinguishing viable pregnancies from those that did not sustain a fetal heart beat through the first trimester. They also were significantly higher for multiple pregnancies, compared with singleton pregnancies.

“What it puts in my mind is, if their first level is below 100, they are probably not going to have a viable pregnancy outcome. … I know to couch my counseling,” Dr. Fong said in an interview.

The investigators reviewed all IVF pregnancies at the New Jersey center from June 1998 to March 2004. A total of 53 patients did not have a fetal heartbeat at the end of the first trimester. Their mean β-HCG levels were 56 mIU/mL on day 16, and 115 mIU/mL on day 18, with an average slope of 24 mIU/mL.

Levels and slopes were much higher for the remaining 269 women with viable pregnancies with mean levels of 216 mIU/mL on day 16 and 505 mIU/mL on day 18, with an average slope of 140 mIU/mL.

Most of the women, 180, had singleton pregnancies. Their average β-HCG levels were 169 mIU/mL on day 16 and 401 mIU/mL on day 18. The researchers noted that the average slope of 111 mIU/mL was 4.62 times higher than in the pregnancies that were not viable.

For the 89 women who had multiple births, average β-HCG levels were 348 mIU/mL on day 16 and 798 mIU/mL on day 18. Their average slope, 220 mIU/mL, was reported as 9.16 times higher than the slope in patients who did not have a fetal heart beat at the end of the first trimester.

Dr. Fong said the group undertook the study because they did not know how to advise patients with β-HCG levels that are low but not low enough to establish that a pregnancy is not viable.

“Are you enthusiastic? Are you guarded? What sort of tone should you take with your patient when giving levels?” she said. “Often they ask what that means, and we were looking for a point when we should be cautious in advising patients about what their pregnancy outcomes are going to be.”

The investigators noted that β-HCG levels and their rate of rise over 48 hours have been used to manage early pregnancy in the absence of ultrasound. They said the threshold has been a rise of 66% or more over 48 hours to predict a viable pregnancy.

This threshold was based on a 20-patient study with a confidence interval of 85% (Obstet. Gynecol. 1981;58:162–6), according to Dr. Fong.

She and her colleagues have noted that the researchers in that study concluded that about 15% of normal intrauterine pregnancies would appear abnormal by this measure, and that diagnosis actually would be delayed beyond 48 hours in an estimated 13% of ectopic pregnancies.

Dr. Fong emphasized that the new study is specific to in vitro fertilization and more accurate with a confidence interval of 95%. Dr. Fong also cautioned, however, that the averages are not absolutes and that the study does not predict pregnancy outcomes beyond the first trimester.

“We are just reporting a fetal heart,” she said. “People miscarry for reasons other than infertility.”

LOS ANGELES — New data from two pilot studies support the use of aromatase inhibitors to promote pregnancy in women with ovulatory dysfunction or unexplained infertility, according to poster presentations at the annual meeting of the Society for Gynecologic Investigation.

In the first randomized study to test anastrozole as an infertility treatment, women who took the aromatase inhibitor before undergoing intrauterine insemination (IUI) had a pregnancy rate comparable overall with those undergoing standard treatment with clomiphene and IUI. Anastrozole cycles appeared to offer an advantage, however, in that they led to more pregnancies in women with polycystic ovary syndrome and generated three times fewer follicles overall.

In the second study, women taking letrozole before undergoing in vitro fertilization (IVF) produced more oocytes and had higher pregnancy rates than those who were treated with a standard protocol of gonadotropins, although the differences between groups were not statistically significant. This study was a randomized feasibility trial in low responders who had failed previous treatments and were scheduled for an aggressive IVF protocol.

Christopher S. Sipe, M.D., lead investigator of the anastrozole study, said in an interview that he believes enough data exist for physicians to start prescribing aromatase inhibitors for infertility patients, but that few will without an indication for infertility from the Food and Drug Administration. “I think you can still use it, but I don't think a lot of people will with the medicolegal aspects in the field,” said Dr. Sipe of the department of ob.gyn. at the University of Iowa Hospitals and Clinics, Iowa City.

The anastrozole trial recruited 50 couples from the University of Iowa Infertility Treatment Center. Patients with tubal factor infertility or severe male factor infertility were excluded.

Women were randomized to receive 1 mg of anastrozole or 100 mg of clomiphene citrate on cycle days 3 through 7. All women received intramuscular injections of 75 IU of purified FSH on days 7 through 11.

On day 12, ultrasounds and measurements of serum estradiol were initiated and performed every other day. If needed, FSH injections continued until a follicle greater than 18 mm was observed and the patient received 10,000 U of human chorionic gonadotropin. IUI followed 36 hours later.

Overall, the cancellation rate was 16% and the pregnancy rate 18% with nine pregnancies achieved. Though the pregnancy rates of 16% with anastrazole and 20% with clomiphene were similar, Dr. Sipe said the trial was too small to draw conclusions.

Serum estradiol was lower with anastrazole, and the investigators proposed that the smaller number of follicles in those patients suggests the aromatase inhibitor could produce fewer multiple births. “This study did not have enough patients to look at the multiple pregnancy rate—you need 1,200 patients or so—but that is what we are thinking,” Dr. Sipe said.

Perhaps the most provocative finding was in women with polycystic ovary syndrome. Anastrozole produced three pregnancies in this group, but clomiphene produced only one. A published study has also found these patients benefitted from letrozole (Fertil. Steril. 2001;75:305–9), so Dr. Sipe said the Iowa investigators plan further studies with anastrozole in this population.

Sonya Kashyap, M.D., worked on the letrozole study presented at the meeting while she was a fellow at the Cornell Center for Reproductive Medicine and Infertility, New York. Her group was able to randomize 55 patients, of whom 48 completed and were eligible for evaluation, according to Dr. Kashyap, now at the University of Ottawa.

The patients willing to enter the study were largely older couples who had nearly exhausted their options. Most fulfilled at least three of five entry criteria, only one of which was required for eligibility.

The study was not blinded but randomized patients by “concealment of allocation” to either a standard protocol of gonadotropins or letrozole before IVF. Physicians did not know which group patients would be in, and Dr. Kashyap maintained in an interview that the outcomes measured protected the study from bias once treatment began.

The final sample was small (26 women on the standard regimen and 22 on letrozole), and the primary outcome data were not statistically significant but trended in favor of the aromatase inhibitor. Compared with the control group, patients treated with letrozole had higher pregnancy rates per cycle started (3/22 vs. 1/26), per retrieval (3/14 vs. 1/16), and per transfer (3/13 vs. 1/14).

LOS ANGELES — New data from two pilot studies support the use of aromatase inhibitors to promote pregnancy in women with ovulatory dysfunction or unexplained infertility, according to poster presentations at the annual meeting of the Society for Gynecologic Investigation.

In the first randomized study to test anastrozole as an infertility treatment, women who took the aromatase inhibitor before undergoing intrauterine insemination (IUI) had a pregnancy rate comparable overall with those undergoing standard treatment with clomiphene and IUI. Anastrozole cycles appeared to offer an advantage, however, in that they led to more pregnancies in women with polycystic ovary syndrome and generated three times fewer follicles overall.

In the second study, women taking letrozole before undergoing in vitro fertilization (IVF) produced more oocytes and had higher pregnancy rates than those who were treated with a standard protocol of gonadotropins, although the differences between groups were not statistically significant. This study was a randomized feasibility trial in low responders who had failed previous treatments and were scheduled for an aggressive IVF protocol.

Christopher S. Sipe, M.D., lead investigator of the anastrozole study, said in an interview that he believes enough data exist for physicians to start prescribing aromatase inhibitors for infertility patients, but that few will without an indication for infertility from the Food and Drug Administration. “I think you can still use it, but I don't think a lot of people will with the medicolegal aspects in the field,” said Dr. Sipe of the department of ob.gyn. at the University of Iowa Hospitals and Clinics, Iowa City.

The anastrozole trial recruited 50 couples from the University of Iowa Infertility Treatment Center. Patients with tubal factor infertility or severe male factor infertility were excluded.

Women were randomized to receive 1 mg of anastrozole or 100 mg of clomiphene citrate on cycle days 3 through 7. All women received intramuscular injections of 75 IU of purified FSH on days 7 through 11.

On day 12, ultrasounds and measurements of serum estradiol were initiated and performed every other day. If needed, FSH injections continued until a follicle greater than 18 mm was observed and the patient received 10,000 U of human chorionic gonadotropin. IUI followed 36 hours later.

Overall, the cancellation rate was 16% and the pregnancy rate 18% with nine pregnancies achieved. Though the pregnancy rates of 16% with anastrazole and 20% with clomiphene were similar, Dr. Sipe said the trial was too small to draw conclusions.

Serum estradiol was lower with anastrazole, and the investigators proposed that the smaller number of follicles in those patients suggests the aromatase inhibitor could produce fewer multiple births. “This study did not have enough patients to look at the multiple pregnancy rate—you need 1,200 patients or so—but that is what we are thinking,” Dr. Sipe said.

Perhaps the most provocative finding was in women with polycystic ovary syndrome. Anastrozole produced three pregnancies in this group, but clomiphene produced only one. A published study has also found these patients benefitted from letrozole (Fertil. Steril. 2001;75:305–9), so Dr. Sipe said the Iowa investigators plan further studies with anastrozole in this population.

Sonya Kashyap, M.D., worked on the letrozole study presented at the meeting while she was a fellow at the Cornell Center for Reproductive Medicine and Infertility, New York. Her group was able to randomize 55 patients, of whom 48 completed and were eligible for evaluation, according to Dr. Kashyap, now at the University of Ottawa.

The patients willing to enter the study were largely older couples who had nearly exhausted their options. Most fulfilled at least three of five entry criteria, only one of which was required for eligibility.

The study was not blinded but randomized patients by “concealment of allocation” to either a standard protocol of gonadotropins or letrozole before IVF. Physicians did not know which group patients would be in, and Dr. Kashyap maintained in an interview that the outcomes measured protected the study from bias once treatment began.

The final sample was small (26 women on the standard regimen and 22 on letrozole), and the primary outcome data were not statistically significant but trended in favor of the aromatase inhibitor. Compared with the control group, patients treated with letrozole had higher pregnancy rates per cycle started (3/22 vs. 1/26), per retrieval (3/14 vs. 1/16), and per transfer (3/13 vs. 1/14).

LOS ANGELES — New data from two pilot studies support the use of aromatase inhibitors to promote pregnancy in women with ovulatory dysfunction or unexplained infertility, according to poster presentations at the annual meeting of the Society for Gynecologic Investigation.

In the first randomized study to test anastrozole as an infertility treatment, women who took the aromatase inhibitor before undergoing intrauterine insemination (IUI) had a pregnancy rate comparable overall with those undergoing standard treatment with clomiphene and IUI. Anastrozole cycles appeared to offer an advantage, however, in that they led to more pregnancies in women with polycystic ovary syndrome and generated three times fewer follicles overall.

In the second study, women taking letrozole before undergoing in vitro fertilization (IVF) produced more oocytes and had higher pregnancy rates than those who were treated with a standard protocol of gonadotropins, although the differences between groups were not statistically significant. This study was a randomized feasibility trial in low responders who had failed previous treatments and were scheduled for an aggressive IVF protocol.

Christopher S. Sipe, M.D., lead investigator of the anastrozole study, said in an interview that he believes enough data exist for physicians to start prescribing aromatase inhibitors for infertility patients, but that few will without an indication for infertility from the Food and Drug Administration. “I think you can still use it, but I don't think a lot of people will with the medicolegal aspects in the field,” said Dr. Sipe of the department of ob.gyn. at the University of Iowa Hospitals and Clinics, Iowa City.

The anastrozole trial recruited 50 couples from the University of Iowa Infertility Treatment Center. Patients with tubal factor infertility or severe male factor infertility were excluded.

Women were randomized to receive 1 mg of anastrozole or 100 mg of clomiphene citrate on cycle days 3 through 7. All women received intramuscular injections of 75 IU of purified FSH on days 7 through 11.

On day 12, ultrasounds and measurements of serum estradiol were initiated and performed every other day. If needed, FSH injections continued until a follicle greater than 18 mm was observed and the patient received 10,000 U of human chorionic gonadotropin. IUI followed 36 hours later.

Overall, the cancellation rate was 16% and the pregnancy rate 18% with nine pregnancies achieved. Though the pregnancy rates of 16% with anastrazole and 20% with clomiphene were similar, Dr. Sipe said the trial was too small to draw conclusions.

Serum estradiol was lower with anastrazole, and the investigators proposed that the smaller number of follicles in those patients suggests the aromatase inhibitor could produce fewer multiple births. “This study did not have enough patients to look at the multiple pregnancy rate—you need 1,200 patients or so—but that is what we are thinking,” Dr. Sipe said.

Perhaps the most provocative finding was in women with polycystic ovary syndrome. Anastrozole produced three pregnancies in this group, but clomiphene produced only one. A published study has also found these patients benefitted from letrozole (Fertil. Steril. 2001;75:305–9), so Dr. Sipe said the Iowa investigators plan further studies with anastrozole in this population.

Sonya Kashyap, M.D., worked on the letrozole study presented at the meeting while she was a fellow at the Cornell Center for Reproductive Medicine and Infertility, New York. Her group was able to randomize 55 patients, of whom 48 completed and were eligible for evaluation, according to Dr. Kashyap, now at the University of Ottawa.

The patients willing to enter the study were largely older couples who had nearly exhausted their options. Most fulfilled at least three of five entry criteria, only one of which was required for eligibility.

The study was not blinded but randomized patients by “concealment of allocation” to either a standard protocol of gonadotropins or letrozole before IVF. Physicians did not know which group patients would be in, and Dr. Kashyap maintained in an interview that the outcomes measured protected the study from bias once treatment began.

The final sample was small (26 women on the standard regimen and 22 on letrozole), and the primary outcome data were not statistically significant but trended in favor of the aromatase inhibitor. Compared with the control group, patients treated with letrozole had higher pregnancy rates per cycle started (3/22 vs. 1/26), per retrieval (3/14 vs. 1/16), and per transfer (3/13 vs. 1/14).

PHOENIX, ARIZ. — Intravenous nicardipine can reduce blood pressure by 15%–20% without impairing blood supply to the brain in hypertensive emergencies, preliminary results from an ongoing case-control study suggest.

Results so far suggest nicardipine therapy might even improve cerebral oxygenation (PbrO₂) in ischemic patients, reported study investigator Varun Puri, M.D. “There was no reduction in oxygen delivery to the brain despite significant reduction in [the fraction of inspired oxygen],” he said at a meeting sponsored by the Society of Critical Care Medicine.

Dr. Puri presented data on 17 patients with acute neurologic disorders, 11 of whom were women. The patients' average age was 57 years, and pathologies included seven subarachnoid hemorrhages, four traumatic brain injuries, three intracerebral hemorrhages, two arteriovenous malformations, and one case of anoxia.

The patients had 36 episodes of hypertensive emergency during the study: 11 from acute cardiovascular syndrome, 14 postoperatively, and 11 after trauma. The nicardipine dose, titrated as clinically indicated to lower blood pressure, ranged from 2.5 mg to 15 mg per hour. The duration of treatment ranged from 12 hours to 10 days.

Dr. Puri reported that systolic blood pressure fell from 175 mm Hg pretreatment to 143 mm Hg at 8 hours after treatment, diastolic blood pressure decreased from 84 mm Hg to 69 mm Hg, and mean arterial blood pressure dropped from 114 mm Hg to 95 mm Hg. All the changes were statistically significant.

Brain tissue monitoring over an 8-hour period showed no significant changes in intracranial pressure or partial brain tissue oxygenation (PbtO₂). Fraction of inspired oxygen (FiO₂) fell from 0.72 to 0.62, a statistically significant difference.

In six patients presenting with cerebral hypoxia, average PbtO₂ was 10.4 mm Hg before treatment with nicardipine, a specific arterial dilator. By 4 hours post treatment, oxygenation had increased to 20.4 mm Hg. At 8 hours, it was 22.2 mm Hg, a statistically significant change.

One severe adverse event was reported: a case of hypotension that responded quickly to a reduction in the nicardipine dose, Dr. Puri said. Five patients eventually required oral antihypertensive agents, and three went on to β-blockers, he said. None had been on β-blockers before the trial, and patients taking two or more agents for hypertension had also been excluded.

The investigators are continuing to enroll patients, said Dr. Puri, of Creighton University Medical Center in Omaha, Neb. Integra LifeSciences Corp., maker of the Licox brain tissue oxygen monitoring system, provided funding for the study.

PHOENIX, ARIZ. — Intravenous nicardipine can reduce blood pressure by 15%–20% without impairing blood supply to the brain in hypertensive emergencies, preliminary results from an ongoing case-control study suggest.

Results so far suggest nicardipine therapy might even improve cerebral oxygenation (PbrO₂) in ischemic patients, reported study investigator Varun Puri, M.D. “There was no reduction in oxygen delivery to the brain despite significant reduction in [the fraction of inspired oxygen],” he said at a meeting sponsored by the Society of Critical Care Medicine.

Dr. Puri presented data on 17 patients with acute neurologic disorders, 11 of whom were women. The patients' average age was 57 years, and pathologies included seven subarachnoid hemorrhages, four traumatic brain injuries, three intracerebral hemorrhages, two arteriovenous malformations, and one case of anoxia.

The patients had 36 episodes of hypertensive emergency during the study: 11 from acute cardiovascular syndrome, 14 postoperatively, and 11 after trauma. The nicardipine dose, titrated as clinically indicated to lower blood pressure, ranged from 2.5 mg to 15 mg per hour. The duration of treatment ranged from 12 hours to 10 days.

Dr. Puri reported that systolic blood pressure fell from 175 mm Hg pretreatment to 143 mm Hg at 8 hours after treatment, diastolic blood pressure decreased from 84 mm Hg to 69 mm Hg, and mean arterial blood pressure dropped from 114 mm Hg to 95 mm Hg. All the changes were statistically significant.

Brain tissue monitoring over an 8-hour period showed no significant changes in intracranial pressure or partial brain tissue oxygenation (PbtO₂). Fraction of inspired oxygen (FiO₂) fell from 0.72 to 0.62, a statistically significant difference.

In six patients presenting with cerebral hypoxia, average PbtO₂ was 10.4 mm Hg before treatment with nicardipine, a specific arterial dilator. By 4 hours post treatment, oxygenation had increased to 20.4 mm Hg. At 8 hours, it was 22.2 mm Hg, a statistically significant change.

One severe adverse event was reported: a case of hypotension that responded quickly to a reduction in the nicardipine dose, Dr. Puri said. Five patients eventually required oral antihypertensive agents, and three went on to β-blockers, he said. None had been on β-blockers before the trial, and patients taking two or more agents for hypertension had also been excluded.

The investigators are continuing to enroll patients, said Dr. Puri, of Creighton University Medical Center in Omaha, Neb. Integra LifeSciences Corp., maker of the Licox brain tissue oxygen monitoring system, provided funding for the study.

PHOENIX, ARIZ. — Intravenous nicardipine can reduce blood pressure by 15%–20% without impairing blood supply to the brain in hypertensive emergencies, preliminary results from an ongoing case-control study suggest.

Results so far suggest nicardipine therapy might even improve cerebral oxygenation (PbrO₂) in ischemic patients, reported study investigator Varun Puri, M.D. “There was no reduction in oxygen delivery to the brain despite significant reduction in [the fraction of inspired oxygen],” he said at a meeting sponsored by the Society of Critical Care Medicine.

Dr. Puri presented data on 17 patients with acute neurologic disorders, 11 of whom were women. The patients' average age was 57 years, and pathologies included seven subarachnoid hemorrhages, four traumatic brain injuries, three intracerebral hemorrhages, two arteriovenous malformations, and one case of anoxia.

The patients had 36 episodes of hypertensive emergency during the study: 11 from acute cardiovascular syndrome, 14 postoperatively, and 11 after trauma. The nicardipine dose, titrated as clinically indicated to lower blood pressure, ranged from 2.5 mg to 15 mg per hour. The duration of treatment ranged from 12 hours to 10 days.

Dr. Puri reported that systolic blood pressure fell from 175 mm Hg pretreatment to 143 mm Hg at 8 hours after treatment, diastolic blood pressure decreased from 84 mm Hg to 69 mm Hg, and mean arterial blood pressure dropped from 114 mm Hg to 95 mm Hg. All the changes were statistically significant.

Brain tissue monitoring over an 8-hour period showed no significant changes in intracranial pressure or partial brain tissue oxygenation (PbtO₂). Fraction of inspired oxygen (FiO₂) fell from 0.72 to 0.62, a statistically significant difference.

In six patients presenting with cerebral hypoxia, average PbtO₂ was 10.4 mm Hg before treatment with nicardipine, a specific arterial dilator. By 4 hours post treatment, oxygenation had increased to 20.4 mm Hg. At 8 hours, it was 22.2 mm Hg, a statistically significant change.

One severe adverse event was reported: a case of hypotension that responded quickly to a reduction in the nicardipine dose, Dr. Puri said. Five patients eventually required oral antihypertensive agents, and three went on to β-blockers, he said. None had been on β-blockers before the trial, and patients taking two or more agents for hypertension had also been excluded.

The investigators are continuing to enroll patients, said Dr. Puri, of Creighton University Medical Center in Omaha, Neb. Integra LifeSciences Corp., maker of the Licox brain tissue oxygen monitoring system, provided funding for the study.