OBG Management

Use metrics for populations, not individuals

Dr. Kanofsky’s commentary on CD metrics is 100% correct. As an ethical question for physicians and society alike, I would ask, is applying metrics to physicians even moral?

As an ObGyn for most of 4 decades, my approach to obstetrics has not changed. In some years, my CD rate was very low, and in others my rate was average. Women must be treated as individuals. Although the industrial revolution increased quality and decreased costs in manufacturing, I do not believe that we can or should apply those principles to our patients.

Government regulators, insurance companies, and many physician leaders have lost sight of the Oath of Maimonides, which states, “May the love of my art actuate me at all times; may neither avarice nor miserliness…engage my mind,”¹ as well as Hippocrates’ ancient observation, “Whatsoever house I may enter, my visit shall be for the convenience and advantage of the patient.”² In addition, in the modern version of the Hippocratic Oath that most schools use today, physicians swear to “apply, for the benefit of the sick, all measures [that] are required...”³—not to the benefit of the government, the federal budget, or an accountable care organization (ACO).

Clearly, the informed consent of a 42-year-old who had in vitro fertilization and has a floating presentation with a low Bishop score and an estimated fetal weight of 4,000 at 40 6/7 weeks must include not only the risks of primary CD but also the risks of a long labor that may result in a CD, the occasional risk of shoulder dystocia, or third- or fourth-degree extension. Not having had a case of shoulder dystocia or a third- or fourth-degree in more than a decade clearly justifies my rationale.

The morbidity of a multiple repeat CD or even a primary CD in an obese woman is significantly more risky than a non-labored elective CD in a woman of normal weight who plans to have only 1 or 2 children. We must individualize our care. Metrics are for populations, not individuals.

Health economists who aggressively advocate lower cesarean rates accept stillbirths and babies with hypoxic ischemic encephalopathy, cerebral palsy, or Erb’s palsy as long as governmental expenditures are lowered. Do the parents of these children get a vote? The majority of practicing physicians like myself feel more aligned with the Hippocratic Oath and the Oath of Maimonides. We believe that we have a moral, ethical, and medical responsibility to the individual patient and not to an ACO or government bean counter.

I would suggest an overarching theme: choice—the freedom to make our own intelligent decisions based on reasonable data and interpretation of the medical literature.

One size does not fit all. So why do those pushing comparative metrics tell us there is only one way to practice obstetrics?

Howard C. Mandel, MD
Los Angeles, California
 

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Use metrics for populations, not individuals

Dr. Kanofsky’s commentary on CD metrics is 100% correct. As an ethical question for physicians and society alike, I would ask, is applying metrics to physicians even moral?

As an ObGyn for most of 4 decades, my approach to obstetrics has not changed. In some years, my CD rate was very low, and in others my rate was average. Women must be treated as individuals. Although the industrial revolution increased quality and decreased costs in manufacturing, I do not believe that we can or should apply those principles to our patients.

Government regulators, insurance companies, and many physician leaders have lost sight of the Oath of Maimonides, which states, “May the love of my art actuate me at all times; may neither avarice nor miserliness…engage my mind,”¹ as well as Hippocrates’ ancient observation, “Whatsoever house I may enter, my visit shall be for the convenience and advantage of the patient.”² In addition, in the modern version of the Hippocratic Oath that most schools use today, physicians swear to “apply, for the benefit of the sick, all measures [that] are required...”³—not to the benefit of the government, the federal budget, or an accountable care organization (ACO).

Clearly, the informed consent of a 42-year-old who had in vitro fertilization and has a floating presentation with a low Bishop score and an estimated fetal weight of 4,000 at 40 6/7 weeks must include not only the risks of primary CD but also the risks of a long labor that may result in a CD, the occasional risk of shoulder dystocia, or third- or fourth-degree extension. Not having had a case of shoulder dystocia or a third- or fourth-degree in more than a decade clearly justifies my rationale.

The morbidity of a multiple repeat CD or even a primary CD in an obese woman is significantly more risky than a non-labored elective CD in a woman of normal weight who plans to have only 1 or 2 children. We must individualize our care. Metrics are for populations, not individuals.

Health economists who aggressively advocate lower cesarean rates accept stillbirths and babies with hypoxic ischemic encephalopathy, cerebral palsy, or Erb’s palsy as long as governmental expenditures are lowered. Do the parents of these children get a vote? The majority of practicing physicians like myself feel more aligned with the Hippocratic Oath and the Oath of Maimonides. We believe that we have a moral, ethical, and medical responsibility to the individual patient and not to an ACO or government bean counter.

I would suggest an overarching theme: choice—the freedom to make our own intelligent decisions based on reasonable data and interpretation of the medical literature.

One size does not fit all. So why do those pushing comparative metrics tell us there is only one way to practice obstetrics?

Howard C. Mandel, MD
Los Angeles, California
 

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Use metrics for populations, not individuals

Dr. Kanofsky’s commentary on CD metrics is 100% correct. As an ethical question for physicians and society alike, I would ask, is applying metrics to physicians even moral?

As an ObGyn for most of 4 decades, my approach to obstetrics has not changed. In some years, my CD rate was very low, and in others my rate was average. Women must be treated as individuals. Although the industrial revolution increased quality and decreased costs in manufacturing, I do not believe that we can or should apply those principles to our patients.

Government regulators, insurance companies, and many physician leaders have lost sight of the Oath of Maimonides, which states, “May the love of my art actuate me at all times; may neither avarice nor miserliness…engage my mind,”¹ as well as Hippocrates’ ancient observation, “Whatsoever house I may enter, my visit shall be for the convenience and advantage of the patient.”² In addition, in the modern version of the Hippocratic Oath that most schools use today, physicians swear to “apply, for the benefit of the sick, all measures [that] are required...”³—not to the benefit of the government, the federal budget, or an accountable care organization (ACO).

Clearly, the informed consent of a 42-year-old who had in vitro fertilization and has a floating presentation with a low Bishop score and an estimated fetal weight of 4,000 at 40 6/7 weeks must include not only the risks of primary CD but also the risks of a long labor that may result in a CD, the occasional risk of shoulder dystocia, or third- or fourth-degree extension. Not having had a case of shoulder dystocia or a third- or fourth-degree in more than a decade clearly justifies my rationale.

The morbidity of a multiple repeat CD or even a primary CD in an obese woman is significantly more risky than a non-labored elective CD in a woman of normal weight who plans to have only 1 or 2 children. We must individualize our care. Metrics are for populations, not individuals.

Health economists who aggressively advocate lower cesarean rates accept stillbirths and babies with hypoxic ischemic encephalopathy, cerebral palsy, or Erb’s palsy as long as governmental expenditures are lowered. Do the parents of these children get a vote? The majority of practicing physicians like myself feel more aligned with the Hippocratic Oath and the Oath of Maimonides. We believe that we have a moral, ethical, and medical responsibility to the individual patient and not to an ACO or government bean counter.

I would suggest an overarching theme: choice—the freedom to make our own intelligent decisions based on reasonable data and interpretation of the medical literature.

One size does not fit all. So why do those pushing comparative metrics tell us there is only one way to practice obstetrics?

Howard C. Mandel, MD
Los Angeles, California
 

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Laparoscopic suturing is an option 

Dr. Lum presented a nicely produced video demonstrating various strategies aimed at facilitating total laparoscopic hysterectomy (TLH) of the very large uterus. Her patient’s evaluation included magnetic resonance imaging. In the video, she demonstrates a variety of interventions, including the use of a preoperative gonadotropin–releasing hormone (GNRH) agonist and immediate perioperative radial artery–uterine artery embolization. Intraoperative techniques include use of ureteral stents and securing the uterine arteries at their origins.

Clearly, TLH of a huge uterus is a technical challenge. However, I’d like to suggest that a relatively basic and important skill would greatly assist in such procedures and likely obviate the need for a GNRH agonist and/or uterine artery embolization. The vessel-sealing devices shown in the video are generally not capable of sealing such large vessels adequately, and this is what leads to the massive hemorrhaging that often occurs.

Laparoscopic suturing with extracorporeal knot tying can  be used effectively to control the extremely large vessels associated with a huge uterus. The judicious placement of sutures can completely control such vessels and prevent bleeding from both proximal and distal ends when 2 sutures are placed and the vessels are transected between the stitches. Many laparoscopic surgeons have come to rely on bipolar energy or ultrasonic devices to coagulate vessels. But when dealing with huge vessels, a return to basics using laparoscopic suturing will greatly benefit the patient and the surgeon by reducing blood loss and operative time.

David L. Zisow, MD
Baltimore, Maryland

Dr. Lum responds

I thank Dr. Zisow for his thoughtful comments. I agree that laparoscopic suturing is an essential skill that can be utilized to suture ligate vessels. If we consider the basics of an open hysterectomy, the uterine artery is clamped first, then suture ligated. When approaching a very large vessel during TLH, I would be concerned that a simple suture around a large vessel might tear through and cause more bleeding. To mitigate this risk, the vessel can be clamped with a grasper first, similar to the approach in an open hysterectomy. However, once a vessel is compressed, a sealing device can usually work just as well as a suture. It becomes a matter of preference and cost.

During hysterectomy of a very large uterus, a big challenge is managing bleeding of the uterus itself during manipulation from above. Bleeding from the vascular sinuses of the myometrium can be brisk and obscure visualization, potentially leading to laparotomy conversion. A common misconception is that uterine artery embolization is equivalent to suturing the uterine arteries. In actuality, the goal of a uterine artery embolization is to embolize the distal branches of the uterine arteries, which can help with any potential bleeding from the uterus itself during hysterectomy.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Laparoscopic suturing is an option 

Dr. Lum presented a nicely produced video demonstrating various strategies aimed at facilitating total laparoscopic hysterectomy (TLH) of the very large uterus. Her patient’s evaluation included magnetic resonance imaging. In the video, she demonstrates a variety of interventions, including the use of a preoperative gonadotropin–releasing hormone (GNRH) agonist and immediate perioperative radial artery–uterine artery embolization. Intraoperative techniques include use of ureteral stents and securing the uterine arteries at their origins.

Clearly, TLH of a huge uterus is a technical challenge. However, I’d like to suggest that a relatively basic and important skill would greatly assist in such procedures and likely obviate the need for a GNRH agonist and/or uterine artery embolization. The vessel-sealing devices shown in the video are generally not capable of sealing such large vessels adequately, and this is what leads to the massive hemorrhaging that often occurs.

Laparoscopic suturing with extracorporeal knot tying can  be used effectively to control the extremely large vessels associated with a huge uterus. The judicious placement of sutures can completely control such vessels and prevent bleeding from both proximal and distal ends when 2 sutures are placed and the vessels are transected between the stitches. Many laparoscopic surgeons have come to rely on bipolar energy or ultrasonic devices to coagulate vessels. But when dealing with huge vessels, a return to basics using laparoscopic suturing will greatly benefit the patient and the surgeon by reducing blood loss and operative time.

David L. Zisow, MD
Baltimore, Maryland

Dr. Lum responds

I thank Dr. Zisow for his thoughtful comments. I agree that laparoscopic suturing is an essential skill that can be utilized to suture ligate vessels. If we consider the basics of an open hysterectomy, the uterine artery is clamped first, then suture ligated. When approaching a very large vessel during TLH, I would be concerned that a simple suture around a large vessel might tear through and cause more bleeding. To mitigate this risk, the vessel can be clamped with a grasper first, similar to the approach in an open hysterectomy. However, once a vessel is compressed, a sealing device can usually work just as well as a suture. It becomes a matter of preference and cost.

During hysterectomy of a very large uterus, a big challenge is managing bleeding of the uterus itself during manipulation from above. Bleeding from the vascular sinuses of the myometrium can be brisk and obscure visualization, potentially leading to laparotomy conversion. A common misconception is that uterine artery embolization is equivalent to suturing the uterine arteries. In actuality, the goal of a uterine artery embolization is to embolize the distal branches of the uterine arteries, which can help with any potential bleeding from the uterus itself during hysterectomy.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Laparoscopic suturing is an option 

Dr. Lum presented a nicely produced video demonstrating various strategies aimed at facilitating total laparoscopic hysterectomy (TLH) of the very large uterus. Her patient’s evaluation included magnetic resonance imaging. In the video, she demonstrates a variety of interventions, including the use of a preoperative gonadotropin–releasing hormone (GNRH) agonist and immediate perioperative radial artery–uterine artery embolization. Intraoperative techniques include use of ureteral stents and securing the uterine arteries at their origins.

Clearly, TLH of a huge uterus is a technical challenge. However, I’d like to suggest that a relatively basic and important skill would greatly assist in such procedures and likely obviate the need for a GNRH agonist and/or uterine artery embolization. The vessel-sealing devices shown in the video are generally not capable of sealing such large vessels adequately, and this is what leads to the massive hemorrhaging that often occurs.

Laparoscopic suturing with extracorporeal knot tying can  be used effectively to control the extremely large vessels associated with a huge uterus. The judicious placement of sutures can completely control such vessels and prevent bleeding from both proximal and distal ends when 2 sutures are placed and the vessels are transected between the stitches. Many laparoscopic surgeons have come to rely on bipolar energy or ultrasonic devices to coagulate vessels. But when dealing with huge vessels, a return to basics using laparoscopic suturing will greatly benefit the patient and the surgeon by reducing blood loss and operative time.

David L. Zisow, MD
Baltimore, Maryland

Dr. Lum responds

I thank Dr. Zisow for his thoughtful comments. I agree that laparoscopic suturing is an essential skill that can be utilized to suture ligate vessels. If we consider the basics of an open hysterectomy, the uterine artery is clamped first, then suture ligated. When approaching a very large vessel during TLH, I would be concerned that a simple suture around a large vessel might tear through and cause more bleeding. To mitigate this risk, the vessel can be clamped with a grasper first, similar to the approach in an open hysterectomy. However, once a vessel is compressed, a sealing device can usually work just as well as a suture. It becomes a matter of preference and cost.

During hysterectomy of a very large uterus, a big challenge is managing bleeding of the uterus itself during manipulation from above. Bleeding from the vascular sinuses of the myometrium can be brisk and obscure visualization, potentially leading to laparotomy conversion. A common misconception is that uterine artery embolization is equivalent to suturing the uterine arteries. In actuality, the goal of a uterine artery embolization is to embolize the distal branches of the uterine arteries, which can help with any potential bleeding from the uterus itself during hysterectomy.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Multiple payment systems impede universal HPV screening access 

Unless the issue of multiple systems of payment and access (that is, multiple insurance companies and providers) can be resolved in the United States, I do not believe there will be an advancement across the board for human papillomavirus (HPV) screening. In my opinion, we need to work toward access to health care for all and a single-payer system.

C.L. Conrad-Forrest, MD
Davis, California

Dr. Barbieri responds

I agree with Dr. Conrad-Forrest that improving cervical cancer screening would be advanced by interoperable electronic medical records and health systems that are designed to manage population health. I predict that a large integrated health system will be the first to adopt the use of high-risk HPV testing to screen for cervical cancer in the United States.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Multiple payment systems impede universal HPV screening access 

Unless the issue of multiple systems of payment and access (that is, multiple insurance companies and providers) can be resolved in the United States, I do not believe there will be an advancement across the board for human papillomavirus (HPV) screening. In my opinion, we need to work toward access to health care for all and a single-payer system.

C.L. Conrad-Forrest, MD
Davis, California

Dr. Barbieri responds

I agree with Dr. Conrad-Forrest that improving cervical cancer screening would be advanced by interoperable electronic medical records and health systems that are designed to manage population health. I predict that a large integrated health system will be the first to adopt the use of high-risk HPV testing to screen for cervical cancer in the United States.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Multiple payment systems impede universal HPV screening access 

Unless the issue of multiple systems of payment and access (that is, multiple insurance companies and providers) can be resolved in the United States, I do not believe there will be an advancement across the board for human papillomavirus (HPV) screening. In my opinion, we need to work toward access to health care for all and a single-payer system.

C.L. Conrad-Forrest, MD
Davis, California

Dr. Barbieri responds

I agree with Dr. Conrad-Forrest that improving cervical cancer screening would be advanced by interoperable electronic medical records and health systems that are designed to manage population health. I predict that a large integrated health system will be the first to adopt the use of high-risk HPV testing to screen for cervical cancer in the United States.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The 2018 meeting of the American Gynecological and Obstetrical Society, held in Philadelphia, Pennsylvania, September 6 to 8, featured a talk by Louis J. Muglia, MD, PhD, on “Evolution, Genetics, and Preterm Birth.” Dr. Muglia, who is Co-Director of the Perinatal Institute, Director of the Center for Prevention of Preterm Birth, and Director of the Division of Human Genetics at the Cincinnati Children’s Hospital Medical Center, discussed his recent research on genetic associations of gestational duration and spontaneous preterm birth and some of his key findings. OBG Management caught up with Dr. Muglia on how he feels the study of the human genome could lead to advancements in the prevention of preterm birth.

OBG Management: You discussed the “genetic architecture of human pregnancy.” Can you define what that is?

The genetic architecture tells us which pathways are activated that initiate birth to occur. By understanding that, we can begin to understand not only the genetic factors that the architecture describes, but also that the genetic architecture is going to be modified in response to environmental stimuli that will disrupt the outcomes. In the future, we will be able to develop biomarkers, predictive genetic algorithms, and other tools that will allow us to assess risk in a way that we can’t right now.

OBG Management: How is gene study adding to the overall knowledge of preterm birth?

Gene study is giving us new pathways to look at. It will give us biomarkers; it will give us targets for potential therapeutic interventions. I mentioned in my talk that one of the genes that we identified in our recent New England Journal of Medicine (NEJM) study pinpointed selenium as an important component and a whole process of determining risk for preterm birth that we never even thought of before. For instance, could there be preventive strategies for prematurity, like we have for neural tube defects and folic acid? The possibility of supplementation with selenium, or other micronutrients that some of the genetic studies will reveal to us in a nonbiased fashion, would not be discovered without the study of genes.

OBG Management : You mentioned your NEJM paper. Can you describe the large data sets that your team used in your gene research?

The discovery cohort, which refers to essentially the biggest compilation, was a wonderful collaboration that we had with the direct-to-consumer genotyping company 23andme. I had contacted them to determine if they had captured any pregnancy-related data, particularly birth-timing information related to individuals who had completed their research surveys. They indicated that they had asked the question, “What was the length of your first pregnancy?” With this information, we were able to get essentially 44,000 responses to that question. That really provided the foundation for the study in the NEJM.

Now, there are caveats with that information, since it was all recollection and self-reported data. We were unsure how accurate it would be. In addition, we did not always know why the delivery occurred—was it spontaneous or was it medically indicated? We were interested in the spontaneous, naturally-occurring preterm birth. Using that as a discovery cohort, with those reservations in mind, we identified 6 genes for birth length. We then asked in a carefully collected series of cohorts that we had amassed on our own, and with collaborators over the years from Finland, Norway, and Denmark, whether those same associations still existed. And every one of them did. Every one of them was validated in our carefully phenotyped cohort. In total, that was about 55,000 women that we had analyzed and studied between the discovery and the validation cohort. Since then, we have accessed another 3 or 4 cohorts, which has increased our sample size even more, so we have identified even more genes than we originally reported in our paper.

OBG Management: What do you identify as the next steps in your research after identifying several genes associated with the timing of birth?

The idea is not just to develop longer and longer lists of genes that are suggested or associated with birth timing phenotypes that we are interested in—either preterm birth or duration of gestation—but to actually understand what they are doing. That is a little bit trickier than saying we have identified genes. We have identified the precise region of mom’s genome that is involved in regulating birth timing, but in many cases I have indicated the closest gene that is involved in birth timing. For some of the regions, however, there are many genes involved, and so is it regulating one pathway, is it regulating many? Which tissue is involved in regulating? Is it in the uterus, in the cervix, or in the immune system? The next steps are to figure out how these things are acting so that we can design better strategies for prevention. The goal is to really bring down preterm birth rates by implementing strategies for prevention and treatment that we don’t currently have.

OBG Management: What is the significance of maternal selenium status and preterm birth risk?

Well, we really don’t know. We identified one of these gene regions, a variant near a factory involved in production of what are called selenoproteins—proteins that incorporate selenium into them. (There are about 25 of those in the human genome.) We identified a genetic risk factor in a region that is linked to the selenoprotein production chain. What we were brought to think about was this: In parts of the world where we know there is substantial selenium deficiency (parts of sub-Saharan Africa, parts of China, parts of Asia), could selenium deficiency itself be contributing to very high rates of preterm birth? Right now we are trying to figure out if there is an association by measuring maternal plasma selenium levels about halfway through pregnancy and then asking what was the outcome from the pregnancy. Are women with low levels of selenium at increased risk for preterm birth? There have been 2 studies published that do already suggest that women with lower selenium levels tend to give birth to premature babies often.

OBG Management : What is the HSPA1L pathway and why is it important for pregnancy outcomes?

In our study where we performed genome-wide association, we looked at what are called common variants in the human genome—common variants in general are carried by more people. They had to be carried by a couple percent of the population to be included in our study. But there is also the thought that individual, more severe variants (that do not necessarily get transmitted because of how severe their effects are), will also affect birth outcomes. So we did a study to sequence mom’s genome to look for these rarities, things that account for less than 1% of the whole population. We were able to identify this gene, HSPA1L, which again, as found in our genome-wide studies, seems to be involved in controlling the strength of the steroid hormone signal, which is very important for maintaining and ending pregnancy. Progesterone and estrogen are the yin and yang of maintaining and ending pregnancy, and we think HSPA1L, the variant we identified, decreases the steroid hormone signal function so that it is not able to regulate that progesterone/estrogen signal the same way anymore.
 

OBG Management: Why is this an exciting time to be studying genes in pregnancy?

To understand how gene study can optimize our knowledge of human pregnancy outcomes really requires a study of human pregnancy specifically, and one of the best opportunities we have is to gather these large data sets. And we can’t forget about collecting pregnancy outcomes on women as part of new National Institutes of Health initiatives that are developing personalized medicine strategies. We looked at 50,000 women in our research, but we have the capacity to look at 500,000 women. As we go from identifying 6 genes to 12 genes to 100 genes, we will be able to understand better how these things are talking to one another and better define the signatures of what tissues are being acted on. We will be able to get sequentially synergistic information that will allow us to solve this in a way we couldn’t before.

The 2018 meeting of the American Gynecological and Obstetrical Society, held in Philadelphia, Pennsylvania, September 6 to 8, featured a talk by Louis J. Muglia, MD, PhD, on “Evolution, Genetics, and Preterm Birth.” Dr. Muglia, who is Co-Director of the Perinatal Institute, Director of the Center for Prevention of Preterm Birth, and Director of the Division of Human Genetics at the Cincinnati Children’s Hospital Medical Center, discussed his recent research on genetic associations of gestational duration and spontaneous preterm birth and some of his key findings. OBG Management caught up with Dr. Muglia on how he feels the study of the human genome could lead to advancements in the prevention of preterm birth.

OBG Management: You discussed the “genetic architecture of human pregnancy.” Can you define what that is?

The genetic architecture tells us which pathways are activated that initiate birth to occur. By understanding that, we can begin to understand not only the genetic factors that the architecture describes, but also that the genetic architecture is going to be modified in response to environmental stimuli that will disrupt the outcomes. In the future, we will be able to develop biomarkers, predictive genetic algorithms, and other tools that will allow us to assess risk in a way that we can’t right now.

OBG Management: How is gene study adding to the overall knowledge of preterm birth?

Gene study is giving us new pathways to look at. It will give us biomarkers; it will give us targets for potential therapeutic interventions. I mentioned in my talk that one of the genes that we identified in our recent New England Journal of Medicine (NEJM) study pinpointed selenium as an important component and a whole process of determining risk for preterm birth that we never even thought of before. For instance, could there be preventive strategies for prematurity, like we have for neural tube defects and folic acid? The possibility of supplementation with selenium, or other micronutrients that some of the genetic studies will reveal to us in a nonbiased fashion, would not be discovered without the study of genes.

OBG Management : You mentioned your NEJM paper. Can you describe the large data sets that your team used in your gene research?

The discovery cohort, which refers to essentially the biggest compilation, was a wonderful collaboration that we had with the direct-to-consumer genotyping company 23andme. I had contacted them to determine if they had captured any pregnancy-related data, particularly birth-timing information related to individuals who had completed their research surveys. They indicated that they had asked the question, “What was the length of your first pregnancy?” With this information, we were able to get essentially 44,000 responses to that question. That really provided the foundation for the study in the NEJM.

Now, there are caveats with that information, since it was all recollection and self-reported data. We were unsure how accurate it would be. In addition, we did not always know why the delivery occurred—was it spontaneous or was it medically indicated? We were interested in the spontaneous, naturally-occurring preterm birth. Using that as a discovery cohort, with those reservations in mind, we identified 6 genes for birth length. We then asked in a carefully collected series of cohorts that we had amassed on our own, and with collaborators over the years from Finland, Norway, and Denmark, whether those same associations still existed. And every one of them did. Every one of them was validated in our carefully phenotyped cohort. In total, that was about 55,000 women that we had analyzed and studied between the discovery and the validation cohort. Since then, we have accessed another 3 or 4 cohorts, which has increased our sample size even more, so we have identified even more genes than we originally reported in our paper.

OBG Management: What do you identify as the next steps in your research after identifying several genes associated with the timing of birth?

The idea is not just to develop longer and longer lists of genes that are suggested or associated with birth timing phenotypes that we are interested in—either preterm birth or duration of gestation—but to actually understand what they are doing. That is a little bit trickier than saying we have identified genes. We have identified the precise region of mom’s genome that is involved in regulating birth timing, but in many cases I have indicated the closest gene that is involved in birth timing. For some of the regions, however, there are many genes involved, and so is it regulating one pathway, is it regulating many? Which tissue is involved in regulating? Is it in the uterus, in the cervix, or in the immune system? The next steps are to figure out how these things are acting so that we can design better strategies for prevention. The goal is to really bring down preterm birth rates by implementing strategies for prevention and treatment that we don’t currently have.

OBG Management: What is the significance of maternal selenium status and preterm birth risk?

Well, we really don’t know. We identified one of these gene regions, a variant near a factory involved in production of what are called selenoproteins—proteins that incorporate selenium into them. (There are about 25 of those in the human genome.) We identified a genetic risk factor in a region that is linked to the selenoprotein production chain. What we were brought to think about was this: In parts of the world where we know there is substantial selenium deficiency (parts of sub-Saharan Africa, parts of China, parts of Asia), could selenium deficiency itself be contributing to very high rates of preterm birth? Right now we are trying to figure out if there is an association by measuring maternal plasma selenium levels about halfway through pregnancy and then asking what was the outcome from the pregnancy. Are women with low levels of selenium at increased risk for preterm birth? There have been 2 studies published that do already suggest that women with lower selenium levels tend to give birth to premature babies often.

OBG Management : What is the HSPA1L pathway and why is it important for pregnancy outcomes?

In our study where we performed genome-wide association, we looked at what are called common variants in the human genome—common variants in general are carried by more people. They had to be carried by a couple percent of the population to be included in our study. But there is also the thought that individual, more severe variants (that do not necessarily get transmitted because of how severe their effects are), will also affect birth outcomes. So we did a study to sequence mom’s genome to look for these rarities, things that account for less than 1% of the whole population. We were able to identify this gene, HSPA1L, which again, as found in our genome-wide studies, seems to be involved in controlling the strength of the steroid hormone signal, which is very important for maintaining and ending pregnancy. Progesterone and estrogen are the yin and yang of maintaining and ending pregnancy, and we think HSPA1L, the variant we identified, decreases the steroid hormone signal function so that it is not able to regulate that progesterone/estrogen signal the same way anymore.
 

OBG Management: Why is this an exciting time to be studying genes in pregnancy?

To understand how gene study can optimize our knowledge of human pregnancy outcomes really requires a study of human pregnancy specifically, and one of the best opportunities we have is to gather these large data sets. And we can’t forget about collecting pregnancy outcomes on women as part of new National Institutes of Health initiatives that are developing personalized medicine strategies. We looked at 50,000 women in our research, but we have the capacity to look at 500,000 women. As we go from identifying 6 genes to 12 genes to 100 genes, we will be able to understand better how these things are talking to one another and better define the signatures of what tissues are being acted on. We will be able to get sequentially synergistic information that will allow us to solve this in a way we couldn’t before.

The 2018 meeting of the American Gynecological and Obstetrical Society, held in Philadelphia, Pennsylvania, September 6 to 8, featured a talk by Louis J. Muglia, MD, PhD, on “Evolution, Genetics, and Preterm Birth.” Dr. Muglia, who is Co-Director of the Perinatal Institute, Director of the Center for Prevention of Preterm Birth, and Director of the Division of Human Genetics at the Cincinnati Children’s Hospital Medical Center, discussed his recent research on genetic associations of gestational duration and spontaneous preterm birth and some of his key findings. OBG Management caught up with Dr. Muglia on how he feels the study of the human genome could lead to advancements in the prevention of preterm birth.

OBG Management: You discussed the “genetic architecture of human pregnancy.” Can you define what that is?

The genetic architecture tells us which pathways are activated that initiate birth to occur. By understanding that, we can begin to understand not only the genetic factors that the architecture describes, but also that the genetic architecture is going to be modified in response to environmental stimuli that will disrupt the outcomes. In the future, we will be able to develop biomarkers, predictive genetic algorithms, and other tools that will allow us to assess risk in a way that we can’t right now.

OBG Management: How is gene study adding to the overall knowledge of preterm birth?

Gene study is giving us new pathways to look at. It will give us biomarkers; it will give us targets for potential therapeutic interventions. I mentioned in my talk that one of the genes that we identified in our recent New England Journal of Medicine (NEJM) study pinpointed selenium as an important component and a whole process of determining risk for preterm birth that we never even thought of before. For instance, could there be preventive strategies for prematurity, like we have for neural tube defects and folic acid? The possibility of supplementation with selenium, or other micronutrients that some of the genetic studies will reveal to us in a nonbiased fashion, would not be discovered without the study of genes.

OBG Management : You mentioned your NEJM paper. Can you describe the large data sets that your team used in your gene research?

The discovery cohort, which refers to essentially the biggest compilation, was a wonderful collaboration that we had with the direct-to-consumer genotyping company 23andme. I had contacted them to determine if they had captured any pregnancy-related data, particularly birth-timing information related to individuals who had completed their research surveys. They indicated that they had asked the question, “What was the length of your first pregnancy?” With this information, we were able to get essentially 44,000 responses to that question. That really provided the foundation for the study in the NEJM.

Now, there are caveats with that information, since it was all recollection and self-reported data. We were unsure how accurate it would be. In addition, we did not always know why the delivery occurred—was it spontaneous or was it medically indicated? We were interested in the spontaneous, naturally-occurring preterm birth. Using that as a discovery cohort, with those reservations in mind, we identified 6 genes for birth length. We then asked in a carefully collected series of cohorts that we had amassed on our own, and with collaborators over the years from Finland, Norway, and Denmark, whether those same associations still existed. And every one of them did. Every one of them was validated in our carefully phenotyped cohort. In total, that was about 55,000 women that we had analyzed and studied between the discovery and the validation cohort. Since then, we have accessed another 3 or 4 cohorts, which has increased our sample size even more, so we have identified even more genes than we originally reported in our paper.

OBG Management: What do you identify as the next steps in your research after identifying several genes associated with the timing of birth?

The idea is not just to develop longer and longer lists of genes that are suggested or associated with birth timing phenotypes that we are interested in—either preterm birth or duration of gestation—but to actually understand what they are doing. That is a little bit trickier than saying we have identified genes. We have identified the precise region of mom’s genome that is involved in regulating birth timing, but in many cases I have indicated the closest gene that is involved in birth timing. For some of the regions, however, there are many genes involved, and so is it regulating one pathway, is it regulating many? Which tissue is involved in regulating? Is it in the uterus, in the cervix, or in the immune system? The next steps are to figure out how these things are acting so that we can design better strategies for prevention. The goal is to really bring down preterm birth rates by implementing strategies for prevention and treatment that we don’t currently have.

OBG Management: What is the significance of maternal selenium status and preterm birth risk?

Well, we really don’t know. We identified one of these gene regions, a variant near a factory involved in production of what are called selenoproteins—proteins that incorporate selenium into them. (There are about 25 of those in the human genome.) We identified a genetic risk factor in a region that is linked to the selenoprotein production chain. What we were brought to think about was this: In parts of the world where we know there is substantial selenium deficiency (parts of sub-Saharan Africa, parts of China, parts of Asia), could selenium deficiency itself be contributing to very high rates of preterm birth? Right now we are trying to figure out if there is an association by measuring maternal plasma selenium levels about halfway through pregnancy and then asking what was the outcome from the pregnancy. Are women with low levels of selenium at increased risk for preterm birth? There have been 2 studies published that do already suggest that women with lower selenium levels tend to give birth to premature babies often.

OBG Management : What is the HSPA1L pathway and why is it important for pregnancy outcomes?

In our study where we performed genome-wide association, we looked at what are called common variants in the human genome—common variants in general are carried by more people. They had to be carried by a couple percent of the population to be included in our study. But there is also the thought that individual, more severe variants (that do not necessarily get transmitted because of how severe their effects are), will also affect birth outcomes. So we did a study to sequence mom’s genome to look for these rarities, things that account for less than 1% of the whole population. We were able to identify this gene, HSPA1L, which again, as found in our genome-wide studies, seems to be involved in controlling the strength of the steroid hormone signal, which is very important for maintaining and ending pregnancy. Progesterone and estrogen are the yin and yang of maintaining and ending pregnancy, and we think HSPA1L, the variant we identified, decreases the steroid hormone signal function so that it is not able to regulate that progesterone/estrogen signal the same way anymore.
 

OBG Management: Why is this an exciting time to be studying genes in pregnancy?

To understand how gene study can optimize our knowledge of human pregnancy outcomes really requires a study of human pregnancy specifically, and one of the best opportunities we have is to gather these large data sets. And we can’t forget about collecting pregnancy outcomes on women as part of new National Institutes of Health initiatives that are developing personalized medicine strategies. We looked at 50,000 women in our research, but we have the capacity to look at 500,000 women. As we go from identifying 6 genes to 12 genes to 100 genes, we will be able to understand better how these things are talking to one another and better define the signatures of what tissues are being acted on. We will be able to get sequentially synergistic information that will allow us to solve this in a way we couldn’t before.

Immunization resources

Current recommended adult (anyone over 18 years old) immunization schedule

ACOG Immunization Champions (ACOG members who have demonstrated exceptional progress in increasing immunization rates among adults and pregnant women in their communities through leadership, innovation, collaboration, and educational activities aimed at following ACOG and CDC guidance.)

Summary of Maternal Immunization Recommendations is a provider resource from ACOG and the Centers for Disease Control and Prevention.

Maternal Immunization Toolkit contains materials, including the Vaccines During Pregnancy Poster, to support ObGyns on recommending the influenza vaccine and the Tdap vaccine to all pregnant patients.

Influenza Immunization During Pregnancy Toolkit

Tdap Immunization Toolkit

Immunization resources

Current recommended adult (anyone over 18 years old) immunization schedule

ACOG Immunization Champions (ACOG members who have demonstrated exceptional progress in increasing immunization rates among adults and pregnant women in their communities through leadership, innovation, collaboration, and educational activities aimed at following ACOG and CDC guidance.)

Summary of Maternal Immunization Recommendations is a provider resource from ACOG and the Centers for Disease Control and Prevention.

Maternal Immunization Toolkit contains materials, including the Vaccines During Pregnancy Poster, to support ObGyns on recommending the influenza vaccine and the Tdap vaccine to all pregnant patients.

Influenza Immunization During Pregnancy Toolkit

Tdap Immunization Toolkit

Immunization resources

Current recommended adult (anyone over 18 years old) immunization schedule

ACOG Immunization Champions (ACOG members who have demonstrated exceptional progress in increasing immunization rates among adults and pregnant women in their communities through leadership, innovation, collaboration, and educational activities aimed at following ACOG and CDC guidance.)

Summary of Maternal Immunization Recommendations is a provider resource from ACOG and the Centers for Disease Control and Prevention.

Maternal Immunization Toolkit contains materials, including the Vaccines During Pregnancy Poster, to support ObGyns on recommending the influenza vaccine and the Tdap vaccine to all pregnant patients.

Influenza Immunization During Pregnancy Toolkit

Tdap Immunization Toolkit

Citation: Grobman WA, Rice MM, Reddy UM, et al; for the Eunice Kennedy Schriver National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network. Labor induction versus expectant management in low-risk nulliparous women. N Engl J Med. 2018;379(6):513–523. doi:10.1056/NEJMoa1800566.

Citation: Grobman WA, Rice MM, Reddy UM, et al; for the Eunice Kennedy Schriver National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network. Labor induction versus expectant management in low-risk nulliparous women. N Engl J Med. 2018;379(6):513–523. doi:10.1056/NEJMoa1800566.

Citation: Grobman WA, Rice MM, Reddy UM, et al; for the Eunice Kennedy Schriver National Institute of Child Health and Human Development Maternal–Fetal Medicine Units Network. Labor induction versus expectant management in low-risk nulliparous women. N Engl J Med. 2018;379(6):513–523. doi:10.1056/NEJMoa1800566.

SURGICAL SITE WOUND THERAPY

PICO NPWT is a negative-pressure wound therapy device to treat surgical site infection (SSI). According to Smith & Nephew, a new meta-analysis demonstrates that the prophylactic application of PICO with AIRLOCK™ Technology significantly reduces surgical site complications by 58%, the rate of dehiscence by 26%, and length of stay by one-half day when compared with standard care.

The PICO System is canister-free and disposable. Patients can be discharged safely with PICO in place. Seven days of therapy are provided in each kit, with 1 pump, 2 dressings, and fixation strips to allow for a dressing change.

PICO uses a 4-layer multifunction dressing design in which the layers work together to ensure that negative pressure is delivered to the wound bed and exudate is removed through absorption and evaporation. Approximately 20% of fluid still remains in the dressing. The top film layer has a high-moisture vapor transmission rate to transpire as much as 80% of the exudate, says Smith & Nephew.

FOR MORE INFORMATION, VISIT: http://www.smith-nephew.com/

SHIELDED LAPAROSCOPIC INSTRUMENTS PREVENT BURNS

Encision’s patented Active Electrode Monitoring (AEM®) Shielded Laparoscopic Instruments eliminate patient burns and the associated complications.

Every 90 minutes in the United States, a patient is severely injured from a stray energy burn during laparoscopic surgery, according to Encision. The AEM® Shielded Instruments are designed to eliminate burns caused by monopolar energy insulation failure and capacitive coupling, reducing complications and re-admissions.

In addition to helping health care professionals improve patient safety in line with a recent FDA safety communication, Active Electrode Monitoring is a recommended practice of AORN and AAGL.

Encision offers a complete line of premium laparoscopic monopolar surgical instruments with integrated AEM® technology as well as complimentary products to improve clinical effectiveness and patient safety, including bipolar and cold instrumentation.

FOR MORE INFORMATION, VISIT: https://www.encision.com/

iSORT: 7-DAY BLUETOOTH PILLBOX

TimerCap has a new Bluetooth-enabled 7-day pill box called the iSort that sends reminders to take medication to a patient’s phone using a free TimerCap App found at the AppStore and Android Market.

The iSort automatically records and stores the times when each door/slot is opened and closed. It knows which door has been used and seamlessly updates the TimerCap App. The app will notify the patient and, if designated, a caregiver, whenever a dose is due or missed using pictures to show what and how many meds are scheduled. More than one iSort box can be used with the app.

iSort provides reminders that help improve adherence to medication dosing instructions and eliminates annoying false alarms, double entries, and unnecessary reminders when pills already have been taken. The portable iSort uses 2 AA batteries that need to be changed about once per year.

FOR MORE INFORMATION, VISIT: https://www.timercap.com/isort

PLATFORM TO COORDINATE HEALTH AND TECHNOLOGY

The American Medical Association (AMA) recently has established a new initiative that introduces a solution to improve, organize, and share health care information. The Integrated Health Model Initiative (IHMI) is a platform that coordinates the health and technology sectors around a common data model. IHMI fills the national imperative to pioneer a shared framework for organizing health data, emphasizing patient-centric information, and refining data elements to those most predictive of better outcomes. The AMA says that evolving available health data to depict a complete picture of a patient’s journey from wellness to illness to treatment and beyond allows health care delivery to fully focus on patient outcomes, goals, and wellness. Participation in IHMI is open to all health care and technology stakeholders.

FOR MORE INFORMATION, VISIT: www.ama-assn.org/ihmi

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice. 

SURGICAL SITE WOUND THERAPY

PICO NPWT is a negative-pressure wound therapy device to treat surgical site infection (SSI). According to Smith & Nephew, a new meta-analysis demonstrates that the prophylactic application of PICO with AIRLOCK™ Technology significantly reduces surgical site complications by 58%, the rate of dehiscence by 26%, and length of stay by one-half day when compared with standard care.

The PICO System is canister-free and disposable. Patients can be discharged safely with PICO in place. Seven days of therapy are provided in each kit, with 1 pump, 2 dressings, and fixation strips to allow for a dressing change.

PICO uses a 4-layer multifunction dressing design in which the layers work together to ensure that negative pressure is delivered to the wound bed and exudate is removed through absorption and evaporation. Approximately 20% of fluid still remains in the dressing. The top film layer has a high-moisture vapor transmission rate to transpire as much as 80% of the exudate, says Smith & Nephew.

FOR MORE INFORMATION, VISIT: http://www.smith-nephew.com/

SHIELDED LAPAROSCOPIC INSTRUMENTS PREVENT BURNS

Encision’s patented Active Electrode Monitoring (AEM®) Shielded Laparoscopic Instruments eliminate patient burns and the associated complications.

Every 90 minutes in the United States, a patient is severely injured from a stray energy burn during laparoscopic surgery, according to Encision. The AEM® Shielded Instruments are designed to eliminate burns caused by monopolar energy insulation failure and capacitive coupling, reducing complications and re-admissions.

In addition to helping health care professionals improve patient safety in line with a recent FDA safety communication, Active Electrode Monitoring is a recommended practice of AORN and AAGL.

Encision offers a complete line of premium laparoscopic monopolar surgical instruments with integrated AEM® technology as well as complimentary products to improve clinical effectiveness and patient safety, including bipolar and cold instrumentation.

FOR MORE INFORMATION, VISIT: https://www.encision.com/

iSORT: 7-DAY BLUETOOTH PILLBOX

TimerCap has a new Bluetooth-enabled 7-day pill box called the iSort that sends reminders to take medication to a patient’s phone using a free TimerCap App found at the AppStore and Android Market.

The iSort automatically records and stores the times when each door/slot is opened and closed. It knows which door has been used and seamlessly updates the TimerCap App. The app will notify the patient and, if designated, a caregiver, whenever a dose is due or missed using pictures to show what and how many meds are scheduled. More than one iSort box can be used with the app.

iSort provides reminders that help improve adherence to medication dosing instructions and eliminates annoying false alarms, double entries, and unnecessary reminders when pills already have been taken. The portable iSort uses 2 AA batteries that need to be changed about once per year.

FOR MORE INFORMATION, VISIT: https://www.timercap.com/isort

PLATFORM TO COORDINATE HEALTH AND TECHNOLOGY

The American Medical Association (AMA) recently has established a new initiative that introduces a solution to improve, organize, and share health care information. The Integrated Health Model Initiative (IHMI) is a platform that coordinates the health and technology sectors around a common data model. IHMI fills the national imperative to pioneer a shared framework for organizing health data, emphasizing patient-centric information, and refining data elements to those most predictive of better outcomes. The AMA says that evolving available health data to depict a complete picture of a patient’s journey from wellness to illness to treatment and beyond allows health care delivery to fully focus on patient outcomes, goals, and wellness. Participation in IHMI is open to all health care and technology stakeholders.

FOR MORE INFORMATION, VISIT: www.ama-assn.org/ihmi

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice. 

SURGICAL SITE WOUND THERAPY

PICO NPWT is a negative-pressure wound therapy device to treat surgical site infection (SSI). According to Smith & Nephew, a new meta-analysis demonstrates that the prophylactic application of PICO with AIRLOCK™ Technology significantly reduces surgical site complications by 58%, the rate of dehiscence by 26%, and length of stay by one-half day when compared with standard care.

The PICO System is canister-free and disposable. Patients can be discharged safely with PICO in place. Seven days of therapy are provided in each kit, with 1 pump, 2 dressings, and fixation strips to allow for a dressing change.

PICO uses a 4-layer multifunction dressing design in which the layers work together to ensure that negative pressure is delivered to the wound bed and exudate is removed through absorption and evaporation. Approximately 20% of fluid still remains in the dressing. The top film layer has a high-moisture vapor transmission rate to transpire as much as 80% of the exudate, says Smith & Nephew.

FOR MORE INFORMATION, VISIT: http://www.smith-nephew.com/

SHIELDED LAPAROSCOPIC INSTRUMENTS PREVENT BURNS

Encision’s patented Active Electrode Monitoring (AEM®) Shielded Laparoscopic Instruments eliminate patient burns and the associated complications.

Every 90 minutes in the United States, a patient is severely injured from a stray energy burn during laparoscopic surgery, according to Encision. The AEM® Shielded Instruments are designed to eliminate burns caused by monopolar energy insulation failure and capacitive coupling, reducing complications and re-admissions.

In addition to helping health care professionals improve patient safety in line with a recent FDA safety communication, Active Electrode Monitoring is a recommended practice of AORN and AAGL.

Encision offers a complete line of premium laparoscopic monopolar surgical instruments with integrated AEM® technology as well as complimentary products to improve clinical effectiveness and patient safety, including bipolar and cold instrumentation.

FOR MORE INFORMATION, VISIT: https://www.encision.com/

iSORT: 7-DAY BLUETOOTH PILLBOX

TimerCap has a new Bluetooth-enabled 7-day pill box called the iSort that sends reminders to take medication to a patient’s phone using a free TimerCap App found at the AppStore and Android Market.

The iSort automatically records and stores the times when each door/slot is opened and closed. It knows which door has been used and seamlessly updates the TimerCap App. The app will notify the patient and, if designated, a caregiver, whenever a dose is due or missed using pictures to show what and how many meds are scheduled. More than one iSort box can be used with the app.

iSort provides reminders that help improve adherence to medication dosing instructions and eliminates annoying false alarms, double entries, and unnecessary reminders when pills already have been taken. The portable iSort uses 2 AA batteries that need to be changed about once per year.

FOR MORE INFORMATION, VISIT: https://www.timercap.com/isort

PLATFORM TO COORDINATE HEALTH AND TECHNOLOGY

The American Medical Association (AMA) recently has established a new initiative that introduces a solution to improve, organize, and share health care information. The Integrated Health Model Initiative (IHMI) is a platform that coordinates the health and technology sectors around a common data model. IHMI fills the national imperative to pioneer a shared framework for organizing health data, emphasizing patient-centric information, and refining data elements to those most predictive of better outcomes. The AMA says that evolving available health data to depict a complete picture of a patient’s journey from wellness to illness to treatment and beyond allows health care delivery to fully focus on patient outcomes, goals, and wellness. Participation in IHMI is open to all health care and technology stakeholders.

FOR MORE INFORMATION, VISIT: www.ama-assn.org/ihmi

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice. 

In recent years, an increasing number of laser and radiofrequency device outpatient treatments have been heralded as safe and effective interventions for various gynecologic conditions. Laser devices and radiofrequency technology rapidly have been incorporated into certain clinical settings, including medical practices specializing in dermatology, plastic surgery, and gynecology. While this developing technology has excellent promise, many clinical and research questions remain unanswered.

Illustration: Kimberly Martens for OBG Management

Concerns about energy-based vaginal treatments

Although marketing material often suggests otherwise, most laser and radiofrequency devices are cleared by the US Food and Drug Administration (FDA) only for nonspecific gynecologic and hematologic interventions. However, both laser and radiofrequency device treatments, performed as outpatient procedures, have been touted as appropriate interventions for many conditions, including female sexual dysfunction, arousal and orgasmic concerns, vaginal laxity, vaginismus, lichen sclerosus, urinary incontinence, and vulvar vestibulitis.

Well-designed studies are needed. Prospective, randomized sham-controlled trials of energy-based devices are rare, and most data in the public domain are derived from case series. Many studies are of short duration with limited follow-up. Randomized controlled trials therefore are warranted and should have stringent inclusion and exclusion criteria. Body dysmorphic syndrome, for example, should be a trial exclusion. Study design for research should include the use of standardized, validated scales and long-term follow-up of participants.

Which specialists have the expertise to offer treatment? Important ethical and medical concerns regarding the technology need to be addressed. A prime concern is determining which health care professional specialist is best qualified to assess and treat underlying gynecologic conditions. It is not uncommon to see internists, emergency medicine providers, family physicians, plastic surgeons, psychiatrists, and dermatologists self-proclaiming their gynecologic “vaginal rejuvenation” expertise.

In my experience, some ObGyns have voiced concern about the diverse medical specialties involved in performing these procedures. Currently, no standard level of training is required to perform them. In addition, those providers lack the training needed to adequately and accurately assess the potential for confounding, underlying gynecologic pathology, and they are inadequately trained to offer patients the full gamut of therapeutic interventions. Many may be unfamiliar with female pelvic anatomy and sexual function and a multidisciplinary treatment paradigm.

We need established standards. A common vernacular, nosology, classification, and decision-tree assessment paradigm for genitopelvic laxity (related to the condition of the pelvic floor and not simply a loose feeling in the vagina) is lacking, which may make research and peer-to-peer discussions difficult.

Which patients are appropriate candidates? Proper patient selection criteria for energy-based vaginal treatment have not been standardized, yet this remains a paramount need. A comprehensive patient evaluation should be performed and include a discussion on the difference between an aesthetic complaint and a functional medical problem. Assessment should include the patient’s level of concern or distress and the impact of her symptoms on her overall quality of life. Patients should be evaluated for body dysmorphic syndrome and relationship discord. A complete physical examination, including a detailed pelvic assessment, often is indicated. A treatment algorithm that incorporates conservative therapies coupled with medical, technologic, and psychologic interventions also should be developed.

Various energy-based devices are available for outpatient procedures

Although the number of procedures performed (such as vaginal rejuvenation, labiaplasty, vulvar liposculpturing, hymenoplasty, G-spot amplification, and O-Shot treatment) for both cosmetic and functional problems has increased, the published scientific data on the procedures’ short- and long-term efficacy and safety are limited. The American College of Obstetricians and Gynecologists (ACOG) published a committee opinion stating that many of these procedures, including “vaginal rejuvenation,” may not be considered medically indicated and may lack scientific merit or ample supportive data to confirm their efficacy and safety.¹ ObGyns should proceed with caution before incorporating these technologic treatments into their medical practice.

Much diversity exists within the device-technology space. The underpinnings of each device vary regarding their proposed mechanism of action and theoretical therapeutic and tissue effect. In device marketing materials, many devices have been claimed to have effects on multiple tissue types (for example, both vaginal mucosa and vulvar tissue), whereas others are said to have more focal and localized effects (that is, targeted behind the hymenal ring). Some are marketed as a one-time treatment, while others require multiple repeated treatments over an extended period. When it comes to published data, adverse effect reporting remains limited and follow-up data often are short term.

Radiofrequency and laser devices are separate and very distinct technologies with similar and differing proposed utilizations. Combining radiofrequency and laser treatments in tandem or sequentially may have clinical utility, but long-term safety may be a concern for lasers.

Radiofrequency-based devices

Typically, radiofrequency device treatments:

• are used for outpatient procedures
• do not require topical anesthesia
• are constructed to emit focused electromagnetic waves
• are applied to vaginal, vulvar, or vaginal introital or vestibular tissue
• deliver energy to the deeper connective tissue of the vaginal wall architecture.

Radiofrequency device energy can be monopolar, unipolar, bipolar, or multipolar depending on design. Design also dictates current and the number of electrodes that pass from the device to the grounding pad. Monopolar is the only type of radiofrequency that has a grounding pad; bipolar and multipolar energy returns to the treatment tip.

Radiofrequency devices typically are FDA 510(k)-cleared devices for nonspecific electrocoagulation and hemostasis for surgical procedures. None are currently FDA cleared in the United States for the treatment of vaginal or vulvar laxity or genitourinary syndrome of menopause (GSM). These energy-based devices aim to induce collagen contraction, neocollagenesis, vascularization, and growth factor infiltration to restore the elasticity and moisture of the underlying vaginal mucosa. Heat shock protein activation and inflammation activation are thought to be the underlying mechanisms of action.^2–5

Treatment outcomes with 2 radiofrequency devices

Multiple prospective small case series studies have reported outcomes of women treated with the ThermiVa (ThermiAesthetics LLC) radiofrequency system.^3,4 Typically, 3 treatments (with a between-treatment interval of 4 to 6 weeks) were applied. The clinical end point temperature had a range of 40°C to 45°C, which was maintained for 3 to 5 minutes per treated zone during 30 minutes’ total treatment time.

Some participants self-reported improvement in vaginal laxity symptoms with the 3 treatments. In addition, women reported subjective improvements in both vaginal atrophy symptoms and sexual function, including positive effect in multiple domains. No serious adverse events were reported in these case series. However, there was no placebo-controlled arm, and validated questionnaires were not used in much of this research.^3,4

In another trial, the ThermiVa system was studied in a cohort of 25 sexually active women with self-reported anorgasmia or increased latency to orgasmic response.⁶ Participants received 3 treatments 4 weeks apart. Approximately three-quarters of the participants reported improved orgasmic responsivity, vaginal lubrication, and clitoral sensitivity. Notably, this research did not use validated questionnaires or a placebo or sham-controlled design. The authors suggested sustained treatment benefits at 9 to 12 months. While repeat treatment was advocated, data were lacking to support the optimal time for repeat treatment efficacy.⁶

A cryogen-cooled monopolar radiofrequency device, the Viveve system (Viveve Medical, Inc) differs from other radiofrequency procedures because it systematically cryogen cools and protects the surface of the vaginal mucosal tissue while heating the underlying structures.

The Viveve system was evaluated in 2 small pilot studies (24 and 30 participants) and in a large, randomized, sham-controlled, prospective trial that included 108 participants (VIVEVE I trial).^5,7,8 Results from both preliminary small studies indicated that participants experienced significant improvement in overall sexual function at 6 months. In one of the small studies (in Japanese women), sustained efficacy at 12 months posttreatment was reported.⁷ Neither small study included a placebo-control arm, but they did include the use of validated questionnaires.

In the VIVEVE I trial (a multicenter international study), treatment in the active group consisted of a single, 30-minute outpatient procedure that delivered 90 J/cm² of radiofrequency energy at the level just behind the hymenal ring behind the vaginal introitus. The sham-treated group received ≤1 J/cm² of energy with a similar machine tip.⁸

Statistically significant improvements were reported in the arousal and orgasm domains of the validated Female Sexual Function Index (FSFI) for the active-treatment group compared with the sham-treated group. In addition, there were statistically significant differences in the FSFI and the Female Sexual Distress Scale–Revised total scores in favor of active treatment. Participants in the active-treatment arm reported statistically significant improvement in overall sexual satisfaction coupled with lowered overall sexual distress.⁸

These data are provocative, since the Viveve treatment demonstrated superior efficacy compared with the sham treatment, and prior evidence demonstrated that medical device trials employing a sham arm often demonstrate particularly large placebo/sham effects.⁹ A confirmatory randomized, sham-controlled multicenter US-based trial is currently underway. At present, the VIVEVE I trial remains the only published, large-scale, randomized, sham-controlled, blinded study of a radiofrequency-based treatment.

New emerging data support the efficacy and safety of this specific radiofrequency treatment in patients with mild to moderate urinary stress incontinence; further studies confirming these outcomes are anticipated. The Viveve system is approved in many countries for various conditions, including urinary incontinence (1 country), sexual function (17 countries), vaginal laxity (41 countries), and electrocoagulation and hemostasis (4 countries, including the United States).

Laser technology devices

Laser (Light Amplification by Stimulated Emission of Radiation) therapy, which uses a carbon dioxide (CO2), argon, YAG, or erbium energy source, also is currently marketed as a method to improve various gynecologic conditions, including genital pelvic relaxation syndrome, vaginal laxity, GSM, lichen sclerosus, and sexual problems such as dyspareunia and arousal or orgasmic disorders.

The CO2 laser therapy device, such as the MonaLisa Touch (DEKA Laser), appears to be very popular and widely available. It delivers fractional CO2 laser energy to the vaginal wall, creating sequential micro traumas that subsequently undergo a healing reaction; the newly healed area has an improved underlying tissue architecture (but at a superficial level). The laser’s proposed mechanism of action is that it ablates only a minute fraction of the superficial lamina propria; it acts primarily to stimulate rapid healing of the tissue, creating new collagen and elastic fibers. There is no evidence of scarring.¹⁰

Treatment outcomes with laser device therapy

Authors of a 2017 study series of CO2 laser treatments in women with moderate to severe GSM found that 84% of participants experienced significant improvement in sexual function, dyspareunia, and otherwise unspecified sexual issues from pretreatment to 12 to 24 months posttreatment.¹¹ These findings are consistent with several other case series and provide supportive evidence for the efficacy and safety of CO2 laser therapy. This technology may be appropriate for the treatment of GSM.

Laser technology shows excellent promise for the treatment of GSM symptoms by virtue of its superficial mechanism of action. In addition, several trials have demonstrated efficacy and safety in breast cancer patient populations.¹² This is particularly interesting since breast cancer treatments, such as aromatase inhibitors (considered a mainstay of cancer treatment), can cause severe atrophic vaginitis. Breast cancer survivors often avoid minimally absorbed local vaginal hormonal products, and over-the-counter products (moisturizers and lubricants) are not widely accepted. Hence, a nonhormonal treatment for distressing GSM symptoms is welcomed in this population.

Pagano and colleagues recently studied 82 breast cancer survivors in whom treatment with vaginal moisturizers and lubricants failed.¹² Participants underwent 3 laser treatment cycles approximately 30 to 40 days apart; they demonstrated improvements in vaginal dryness, vaginal itchiness, stinging, dyspareunia, and reduced sensitivity.

Microablative fractional CO2 laser may help reestablish a normative vaginal microbiome by altering the prevalence of lactobacillus species and reestablishing a normative postmenopausal vaginal flora.¹³

The tracking and reporting of adverse events associated with laser procedures has been less than optimal. In my personal clinical experience, consequences from both short- and long-term laser treatments have included vaginal canal agglutination, worsening dyspareunia, and constricture causing vaginal hemorrhage.

Cruz and colleagues recently conducted a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy of fractional CO2 laser compared with topical estriol and laser plus estriol for the treatment of vaginal atrophy in 45 postmenopausal women.¹⁴ They found statistically significant differences in dyspareunia, dryness, and burning compared with baseline levels in all 3 treatment groups. Results with the fractional CO2 laser treatment were deemed to be similar to those of the topical estriol and the combined therapy.¹⁴

By contrast, an erbium (Er):YAG laser, such as the IntimaLase (Fotona, LLC) laser, functions by heating the pelvic tissue and collagen within the introitus and vaginal canal.^15,16 When the underlying collagen is heated, the fibers are thought to thicken and shorten, which may result in immediate contracture of the treated tissue. Additionally, this process stimulates the existing collagen to undergo remodeling and it also may cause neocollagen deposition.¹⁵ In a general review of gynecologic procedures, after 1 to 4 treatment sessions (depending on the study), most patients reported improved sexual satisfaction or vaginal tightness.¹⁵

Although trials have included small numbers of patients, early evidence suggests some lasers with reportedly deeper penetration may be useful for treatment of vaginal laxity, but further studies are needed. In smaller studies, the Er:YAG laser has shown efficacy and safety in the treatment of stress urinary incontinence and improved lower urinary tract symptoms, quality of life, and sexual function.^16,17

Insurance does not cover energy-based treatment costs

Currently, both laser and radiofrequency device treatments are considered fee-for-service interventions. Radiofrequency and laser treatments for gynecologic conditions are not covered by health insurance, and treatment costs can be prohibitive for many patients. In addition, the long-term safety of these treatments remains to be studied further, and the optimal time for a repeat procedure has yet to be elucidated.

The FDA cautions against energy-based procedures

In July 2018, the FDA released a statement of concern reiterating the need for research and randomized clinical trials before energy-based device treatments can be widely accepted, and that they are currently cleared only for general gynecologic indications and not for disorders and symptoms related to menopause, urinary incontinence, or sexual function.¹⁸

The FDA stated that “we have not cleared or approved for marketing any energy-based devices to treat these symptoms or conditions [vaginal laxity; vaginal atrophy, dryness, or itching; pain during sexual intercourse; pain during urination; decreased sexual sensation], or any symptoms related to menopause, urinary incontinence, or sexual function.” The FDA noted that serious complications have been reported, including vaginal burns, scarring, pain during sexual intercourse, and recurring, chronic pain. The FDA issued letters to 7 companies regarding concerns about the marketing of their devices for off-label use and promotion.

Several societies have responded. ACOG reaffirmed its 2016 position statement on fractional laser treatment of vulvovaginal atrophy.¹⁹ JoAnn Pinkerton, MD, Executive Director of The North American Menopause Society (NAMS), and Sheryl Kingsberg, PhD, President of NAMS, alerted their members that both health care professionals and consumers should tread cautiously, and they encouraged scrutiny of existing evidence as all energy-based treatments are not created equal.²⁰ They noted that some research does exist and cited 2 randomized, sham-controlled clinical trials that have been published.

Looking forward

Various novel technologic therapies are entering the gynecologic market. ObGyns must critically evaluate these emerging technologies with a keen understanding of their underlying mechanism of action, the level of scientific evidence, and the treatment’s proposed therapeutic value.

Radiofrequency energy devices appear to be better positioned to treat urinary incontinence and vaginal relaxation syndrome because of their capability for deep tissue penetration. Current data show that laser technology has excellent promise for the treatment and management of GSM. Both technologies warrant further investigation in long-term randomized, sham-controlled trials that assess efficacy and safety with validated instruments over an extended period. In addition, should these technologies prove useful in the overall treatment armamentarium for gynecologic conditions, the question of affordability and insurance coverage needs to be addressed.

ObGyns must advocate for female sexual wellness and encourage a comprehensive multidisciplinary team approach for offering various therapies. Ultimately, responsible use of evidence-based innovative technology should be incorporated into the treatment paradigm.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

In recent years, an increasing number of laser and radiofrequency device outpatient treatments have been heralded as safe and effective interventions for various gynecologic conditions. Laser devices and radiofrequency technology rapidly have been incorporated into certain clinical settings, including medical practices specializing in dermatology, plastic surgery, and gynecology. While this developing technology has excellent promise, many clinical and research questions remain unanswered.

Illustration: Kimberly Martens for OBG Management

Concerns about energy-based vaginal treatments

Although marketing material often suggests otherwise, most laser and radiofrequency devices are cleared by the US Food and Drug Administration (FDA) only for nonspecific gynecologic and hematologic interventions. However, both laser and radiofrequency device treatments, performed as outpatient procedures, have been touted as appropriate interventions for many conditions, including female sexual dysfunction, arousal and orgasmic concerns, vaginal laxity, vaginismus, lichen sclerosus, urinary incontinence, and vulvar vestibulitis.

Well-designed studies are needed. Prospective, randomized sham-controlled trials of energy-based devices are rare, and most data in the public domain are derived from case series. Many studies are of short duration with limited follow-up. Randomized controlled trials therefore are warranted and should have stringent inclusion and exclusion criteria. Body dysmorphic syndrome, for example, should be a trial exclusion. Study design for research should include the use of standardized, validated scales and long-term follow-up of participants.

Which specialists have the expertise to offer treatment? Important ethical and medical concerns regarding the technology need to be addressed. A prime concern is determining which health care professional specialist is best qualified to assess and treat underlying gynecologic conditions. It is not uncommon to see internists, emergency medicine providers, family physicians, plastic surgeons, psychiatrists, and dermatologists self-proclaiming their gynecologic “vaginal rejuvenation” expertise.

In my experience, some ObGyns have voiced concern about the diverse medical specialties involved in performing these procedures. Currently, no standard level of training is required to perform them. In addition, those providers lack the training needed to adequately and accurately assess the potential for confounding, underlying gynecologic pathology, and they are inadequately trained to offer patients the full gamut of therapeutic interventions. Many may be unfamiliar with female pelvic anatomy and sexual function and a multidisciplinary treatment paradigm.

We need established standards. A common vernacular, nosology, classification, and decision-tree assessment paradigm for genitopelvic laxity (related to the condition of the pelvic floor and not simply a loose feeling in the vagina) is lacking, which may make research and peer-to-peer discussions difficult.

Which patients are appropriate candidates? Proper patient selection criteria for energy-based vaginal treatment have not been standardized, yet this remains a paramount need. A comprehensive patient evaluation should be performed and include a discussion on the difference between an aesthetic complaint and a functional medical problem. Assessment should include the patient’s level of concern or distress and the impact of her symptoms on her overall quality of life. Patients should be evaluated for body dysmorphic syndrome and relationship discord. A complete physical examination, including a detailed pelvic assessment, often is indicated. A treatment algorithm that incorporates conservative therapies coupled with medical, technologic, and psychologic interventions also should be developed.

Various energy-based devices are available for outpatient procedures

Although the number of procedures performed (such as vaginal rejuvenation, labiaplasty, vulvar liposculpturing, hymenoplasty, G-spot amplification, and O-Shot treatment) for both cosmetic and functional problems has increased, the published scientific data on the procedures’ short- and long-term efficacy and safety are limited. The American College of Obstetricians and Gynecologists (ACOG) published a committee opinion stating that many of these procedures, including “vaginal rejuvenation,” may not be considered medically indicated and may lack scientific merit or ample supportive data to confirm their efficacy and safety.¹ ObGyns should proceed with caution before incorporating these technologic treatments into their medical practice.

Much diversity exists within the device-technology space. The underpinnings of each device vary regarding their proposed mechanism of action and theoretical therapeutic and tissue effect. In device marketing materials, many devices have been claimed to have effects on multiple tissue types (for example, both vaginal mucosa and vulvar tissue), whereas others are said to have more focal and localized effects (that is, targeted behind the hymenal ring). Some are marketed as a one-time treatment, while others require multiple repeated treatments over an extended period. When it comes to published data, adverse effect reporting remains limited and follow-up data often are short term.

Radiofrequency and laser devices are separate and very distinct technologies with similar and differing proposed utilizations. Combining radiofrequency and laser treatments in tandem or sequentially may have clinical utility, but long-term safety may be a concern for lasers.

Radiofrequency-based devices

Typically, radiofrequency device treatments:

• are used for outpatient procedures
• do not require topical anesthesia
• are constructed to emit focused electromagnetic waves
• are applied to vaginal, vulvar, or vaginal introital or vestibular tissue
• deliver energy to the deeper connective tissue of the vaginal wall architecture.

Radiofrequency device energy can be monopolar, unipolar, bipolar, or multipolar depending on design. Design also dictates current and the number of electrodes that pass from the device to the grounding pad. Monopolar is the only type of radiofrequency that has a grounding pad; bipolar and multipolar energy returns to the treatment tip.

Radiofrequency devices typically are FDA 510(k)-cleared devices for nonspecific electrocoagulation and hemostasis for surgical procedures. None are currently FDA cleared in the United States for the treatment of vaginal or vulvar laxity or genitourinary syndrome of menopause (GSM). These energy-based devices aim to induce collagen contraction, neocollagenesis, vascularization, and growth factor infiltration to restore the elasticity and moisture of the underlying vaginal mucosa. Heat shock protein activation and inflammation activation are thought to be the underlying mechanisms of action.^2–5

Treatment outcomes with 2 radiofrequency devices

Multiple prospective small case series studies have reported outcomes of women treated with the ThermiVa (ThermiAesthetics LLC) radiofrequency system.^3,4 Typically, 3 treatments (with a between-treatment interval of 4 to 6 weeks) were applied. The clinical end point temperature had a range of 40°C to 45°C, which was maintained for 3 to 5 minutes per treated zone during 30 minutes’ total treatment time.

Some participants self-reported improvement in vaginal laxity symptoms with the 3 treatments. In addition, women reported subjective improvements in both vaginal atrophy symptoms and sexual function, including positive effect in multiple domains. No serious adverse events were reported in these case series. However, there was no placebo-controlled arm, and validated questionnaires were not used in much of this research.^3,4

In another trial, the ThermiVa system was studied in a cohort of 25 sexually active women with self-reported anorgasmia or increased latency to orgasmic response.⁶ Participants received 3 treatments 4 weeks apart. Approximately three-quarters of the participants reported improved orgasmic responsivity, vaginal lubrication, and clitoral sensitivity. Notably, this research did not use validated questionnaires or a placebo or sham-controlled design. The authors suggested sustained treatment benefits at 9 to 12 months. While repeat treatment was advocated, data were lacking to support the optimal time for repeat treatment efficacy.⁶

A cryogen-cooled monopolar radiofrequency device, the Viveve system (Viveve Medical, Inc) differs from other radiofrequency procedures because it systematically cryogen cools and protects the surface of the vaginal mucosal tissue while heating the underlying structures.

The Viveve system was evaluated in 2 small pilot studies (24 and 30 participants) and in a large, randomized, sham-controlled, prospective trial that included 108 participants (VIVEVE I trial).^5,7,8 Results from both preliminary small studies indicated that participants experienced significant improvement in overall sexual function at 6 months. In one of the small studies (in Japanese women), sustained efficacy at 12 months posttreatment was reported.⁷ Neither small study included a placebo-control arm, but they did include the use of validated questionnaires.

In the VIVEVE I trial (a multicenter international study), treatment in the active group consisted of a single, 30-minute outpatient procedure that delivered 90 J/cm² of radiofrequency energy at the level just behind the hymenal ring behind the vaginal introitus. The sham-treated group received ≤1 J/cm² of energy with a similar machine tip.⁸

Statistically significant improvements were reported in the arousal and orgasm domains of the validated Female Sexual Function Index (FSFI) for the active-treatment group compared with the sham-treated group. In addition, there were statistically significant differences in the FSFI and the Female Sexual Distress Scale–Revised total scores in favor of active treatment. Participants in the active-treatment arm reported statistically significant improvement in overall sexual satisfaction coupled with lowered overall sexual distress.⁸

These data are provocative, since the Viveve treatment demonstrated superior efficacy compared with the sham treatment, and prior evidence demonstrated that medical device trials employing a sham arm often demonstrate particularly large placebo/sham effects.⁹ A confirmatory randomized, sham-controlled multicenter US-based trial is currently underway. At present, the VIVEVE I trial remains the only published, large-scale, randomized, sham-controlled, blinded study of a radiofrequency-based treatment.

New emerging data support the efficacy and safety of this specific radiofrequency treatment in patients with mild to moderate urinary stress incontinence; further studies confirming these outcomes are anticipated. The Viveve system is approved in many countries for various conditions, including urinary incontinence (1 country), sexual function (17 countries), vaginal laxity (41 countries), and electrocoagulation and hemostasis (4 countries, including the United States).

Laser technology devices

Laser (Light Amplification by Stimulated Emission of Radiation) therapy, which uses a carbon dioxide (CO2), argon, YAG, or erbium energy source, also is currently marketed as a method to improve various gynecologic conditions, including genital pelvic relaxation syndrome, vaginal laxity, GSM, lichen sclerosus, and sexual problems such as dyspareunia and arousal or orgasmic disorders.

The CO2 laser therapy device, such as the MonaLisa Touch (DEKA Laser), appears to be very popular and widely available. It delivers fractional CO2 laser energy to the vaginal wall, creating sequential micro traumas that subsequently undergo a healing reaction; the newly healed area has an improved underlying tissue architecture (but at a superficial level). The laser’s proposed mechanism of action is that it ablates only a minute fraction of the superficial lamina propria; it acts primarily to stimulate rapid healing of the tissue, creating new collagen and elastic fibers. There is no evidence of scarring.¹⁰

Treatment outcomes with laser device therapy

Authors of a 2017 study series of CO2 laser treatments in women with moderate to severe GSM found that 84% of participants experienced significant improvement in sexual function, dyspareunia, and otherwise unspecified sexual issues from pretreatment to 12 to 24 months posttreatment.¹¹ These findings are consistent with several other case series and provide supportive evidence for the efficacy and safety of CO2 laser therapy. This technology may be appropriate for the treatment of GSM.

Laser technology shows excellent promise for the treatment of GSM symptoms by virtue of its superficial mechanism of action. In addition, several trials have demonstrated efficacy and safety in breast cancer patient populations.¹² This is particularly interesting since breast cancer treatments, such as aromatase inhibitors (considered a mainstay of cancer treatment), can cause severe atrophic vaginitis. Breast cancer survivors often avoid minimally absorbed local vaginal hormonal products, and over-the-counter products (moisturizers and lubricants) are not widely accepted. Hence, a nonhormonal treatment for distressing GSM symptoms is welcomed in this population.

Pagano and colleagues recently studied 82 breast cancer survivors in whom treatment with vaginal moisturizers and lubricants failed.¹² Participants underwent 3 laser treatment cycles approximately 30 to 40 days apart; they demonstrated improvements in vaginal dryness, vaginal itchiness, stinging, dyspareunia, and reduced sensitivity.

Microablative fractional CO2 laser may help reestablish a normative vaginal microbiome by altering the prevalence of lactobacillus species and reestablishing a normative postmenopausal vaginal flora.¹³

The tracking and reporting of adverse events associated with laser procedures has been less than optimal. In my personal clinical experience, consequences from both short- and long-term laser treatments have included vaginal canal agglutination, worsening dyspareunia, and constricture causing vaginal hemorrhage.

Cruz and colleagues recently conducted a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy of fractional CO2 laser compared with topical estriol and laser plus estriol for the treatment of vaginal atrophy in 45 postmenopausal women.¹⁴ They found statistically significant differences in dyspareunia, dryness, and burning compared with baseline levels in all 3 treatment groups. Results with the fractional CO2 laser treatment were deemed to be similar to those of the topical estriol and the combined therapy.¹⁴

By contrast, an erbium (Er):YAG laser, such as the IntimaLase (Fotona, LLC) laser, functions by heating the pelvic tissue and collagen within the introitus and vaginal canal.^15,16 When the underlying collagen is heated, the fibers are thought to thicken and shorten, which may result in immediate contracture of the treated tissue. Additionally, this process stimulates the existing collagen to undergo remodeling and it also may cause neocollagen deposition.¹⁵ In a general review of gynecologic procedures, after 1 to 4 treatment sessions (depending on the study), most patients reported improved sexual satisfaction or vaginal tightness.¹⁵

Although trials have included small numbers of patients, early evidence suggests some lasers with reportedly deeper penetration may be useful for treatment of vaginal laxity, but further studies are needed. In smaller studies, the Er:YAG laser has shown efficacy and safety in the treatment of stress urinary incontinence and improved lower urinary tract symptoms, quality of life, and sexual function.^16,17

Insurance does not cover energy-based treatment costs

Currently, both laser and radiofrequency device treatments are considered fee-for-service interventions. Radiofrequency and laser treatments for gynecologic conditions are not covered by health insurance, and treatment costs can be prohibitive for many patients. In addition, the long-term safety of these treatments remains to be studied further, and the optimal time for a repeat procedure has yet to be elucidated.

The FDA cautions against energy-based procedures

In July 2018, the FDA released a statement of concern reiterating the need for research and randomized clinical trials before energy-based device treatments can be widely accepted, and that they are currently cleared only for general gynecologic indications and not for disorders and symptoms related to menopause, urinary incontinence, or sexual function.¹⁸

The FDA stated that “we have not cleared or approved for marketing any energy-based devices to treat these symptoms or conditions [vaginal laxity; vaginal atrophy, dryness, or itching; pain during sexual intercourse; pain during urination; decreased sexual sensation], or any symptoms related to menopause, urinary incontinence, or sexual function.” The FDA noted that serious complications have been reported, including vaginal burns, scarring, pain during sexual intercourse, and recurring, chronic pain. The FDA issued letters to 7 companies regarding concerns about the marketing of their devices for off-label use and promotion.

Several societies have responded. ACOG reaffirmed its 2016 position statement on fractional laser treatment of vulvovaginal atrophy.¹⁹ JoAnn Pinkerton, MD, Executive Director of The North American Menopause Society (NAMS), and Sheryl Kingsberg, PhD, President of NAMS, alerted their members that both health care professionals and consumers should tread cautiously, and they encouraged scrutiny of existing evidence as all energy-based treatments are not created equal.²⁰ They noted that some research does exist and cited 2 randomized, sham-controlled clinical trials that have been published.

Looking forward

Various novel technologic therapies are entering the gynecologic market. ObGyns must critically evaluate these emerging technologies with a keen understanding of their underlying mechanism of action, the level of scientific evidence, and the treatment’s proposed therapeutic value.

Radiofrequency energy devices appear to be better positioned to treat urinary incontinence and vaginal relaxation syndrome because of their capability for deep tissue penetration. Current data show that laser technology has excellent promise for the treatment and management of GSM. Both technologies warrant further investigation in long-term randomized, sham-controlled trials that assess efficacy and safety with validated instruments over an extended period. In addition, should these technologies prove useful in the overall treatment armamentarium for gynecologic conditions, the question of affordability and insurance coverage needs to be addressed.

ObGyns must advocate for female sexual wellness and encourage a comprehensive multidisciplinary team approach for offering various therapies. Ultimately, responsible use of evidence-based innovative technology should be incorporated into the treatment paradigm.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

In recent years, an increasing number of laser and radiofrequency device outpatient treatments have been heralded as safe and effective interventions for various gynecologic conditions. Laser devices and radiofrequency technology rapidly have been incorporated into certain clinical settings, including medical practices specializing in dermatology, plastic surgery, and gynecology. While this developing technology has excellent promise, many clinical and research questions remain unanswered.

Illustration: Kimberly Martens for OBG Management

Concerns about energy-based vaginal treatments

Although marketing material often suggests otherwise, most laser and radiofrequency devices are cleared by the US Food and Drug Administration (FDA) only for nonspecific gynecologic and hematologic interventions. However, both laser and radiofrequency device treatments, performed as outpatient procedures, have been touted as appropriate interventions for many conditions, including female sexual dysfunction, arousal and orgasmic concerns, vaginal laxity, vaginismus, lichen sclerosus, urinary incontinence, and vulvar vestibulitis.

Well-designed studies are needed. Prospective, randomized sham-controlled trials of energy-based devices are rare, and most data in the public domain are derived from case series. Many studies are of short duration with limited follow-up. Randomized controlled trials therefore are warranted and should have stringent inclusion and exclusion criteria. Body dysmorphic syndrome, for example, should be a trial exclusion. Study design for research should include the use of standardized, validated scales and long-term follow-up of participants.

Which specialists have the expertise to offer treatment? Important ethical and medical concerns regarding the technology need to be addressed. A prime concern is determining which health care professional specialist is best qualified to assess and treat underlying gynecologic conditions. It is not uncommon to see internists, emergency medicine providers, family physicians, plastic surgeons, psychiatrists, and dermatologists self-proclaiming their gynecologic “vaginal rejuvenation” expertise.

In my experience, some ObGyns have voiced concern about the diverse medical specialties involved in performing these procedures. Currently, no standard level of training is required to perform them. In addition, those providers lack the training needed to adequately and accurately assess the potential for confounding, underlying gynecologic pathology, and they are inadequately trained to offer patients the full gamut of therapeutic interventions. Many may be unfamiliar with female pelvic anatomy and sexual function and a multidisciplinary treatment paradigm.

We need established standards. A common vernacular, nosology, classification, and decision-tree assessment paradigm for genitopelvic laxity (related to the condition of the pelvic floor and not simply a loose feeling in the vagina) is lacking, which may make research and peer-to-peer discussions difficult.

Which patients are appropriate candidates? Proper patient selection criteria for energy-based vaginal treatment have not been standardized, yet this remains a paramount need. A comprehensive patient evaluation should be performed and include a discussion on the difference between an aesthetic complaint and a functional medical problem. Assessment should include the patient’s level of concern or distress and the impact of her symptoms on her overall quality of life. Patients should be evaluated for body dysmorphic syndrome and relationship discord. A complete physical examination, including a detailed pelvic assessment, often is indicated. A treatment algorithm that incorporates conservative therapies coupled with medical, technologic, and psychologic interventions also should be developed.

Various energy-based devices are available for outpatient procedures

Although the number of procedures performed (such as vaginal rejuvenation, labiaplasty, vulvar liposculpturing, hymenoplasty, G-spot amplification, and O-Shot treatment) for both cosmetic and functional problems has increased, the published scientific data on the procedures’ short- and long-term efficacy and safety are limited. The American College of Obstetricians and Gynecologists (ACOG) published a committee opinion stating that many of these procedures, including “vaginal rejuvenation,” may not be considered medically indicated and may lack scientific merit or ample supportive data to confirm their efficacy and safety.¹ ObGyns should proceed with caution before incorporating these technologic treatments into their medical practice.

Much diversity exists within the device-technology space. The underpinnings of each device vary regarding their proposed mechanism of action and theoretical therapeutic and tissue effect. In device marketing materials, many devices have been claimed to have effects on multiple tissue types (for example, both vaginal mucosa and vulvar tissue), whereas others are said to have more focal and localized effects (that is, targeted behind the hymenal ring). Some are marketed as a one-time treatment, while others require multiple repeated treatments over an extended period. When it comes to published data, adverse effect reporting remains limited and follow-up data often are short term.

Radiofrequency and laser devices are separate and very distinct technologies with similar and differing proposed utilizations. Combining radiofrequency and laser treatments in tandem or sequentially may have clinical utility, but long-term safety may be a concern for lasers.

Radiofrequency-based devices

Typically, radiofrequency device treatments:

• are used for outpatient procedures
• do not require topical anesthesia
• are constructed to emit focused electromagnetic waves
• are applied to vaginal, vulvar, or vaginal introital or vestibular tissue
• deliver energy to the deeper connective tissue of the vaginal wall architecture.

Radiofrequency device energy can be monopolar, unipolar, bipolar, or multipolar depending on design. Design also dictates current and the number of electrodes that pass from the device to the grounding pad. Monopolar is the only type of radiofrequency that has a grounding pad; bipolar and multipolar energy returns to the treatment tip.

Radiofrequency devices typically are FDA 510(k)-cleared devices for nonspecific electrocoagulation and hemostasis for surgical procedures. None are currently FDA cleared in the United States for the treatment of vaginal or vulvar laxity or genitourinary syndrome of menopause (GSM). These energy-based devices aim to induce collagen contraction, neocollagenesis, vascularization, and growth factor infiltration to restore the elasticity and moisture of the underlying vaginal mucosa. Heat shock protein activation and inflammation activation are thought to be the underlying mechanisms of action.^2–5

Treatment outcomes with 2 radiofrequency devices

Multiple prospective small case series studies have reported outcomes of women treated with the ThermiVa (ThermiAesthetics LLC) radiofrequency system.^3,4 Typically, 3 treatments (with a between-treatment interval of 4 to 6 weeks) were applied. The clinical end point temperature had a range of 40°C to 45°C, which was maintained for 3 to 5 minutes per treated zone during 30 minutes’ total treatment time.

Some participants self-reported improvement in vaginal laxity symptoms with the 3 treatments. In addition, women reported subjective improvements in both vaginal atrophy symptoms and sexual function, including positive effect in multiple domains. No serious adverse events were reported in these case series. However, there was no placebo-controlled arm, and validated questionnaires were not used in much of this research.^3,4

In another trial, the ThermiVa system was studied in a cohort of 25 sexually active women with self-reported anorgasmia or increased latency to orgasmic response.⁶ Participants received 3 treatments 4 weeks apart. Approximately three-quarters of the participants reported improved orgasmic responsivity, vaginal lubrication, and clitoral sensitivity. Notably, this research did not use validated questionnaires or a placebo or sham-controlled design. The authors suggested sustained treatment benefits at 9 to 12 months. While repeat treatment was advocated, data were lacking to support the optimal time for repeat treatment efficacy.⁶

A cryogen-cooled monopolar radiofrequency device, the Viveve system (Viveve Medical, Inc) differs from other radiofrequency procedures because it systematically cryogen cools and protects the surface of the vaginal mucosal tissue while heating the underlying structures.

The Viveve system was evaluated in 2 small pilot studies (24 and 30 participants) and in a large, randomized, sham-controlled, prospective trial that included 108 participants (VIVEVE I trial).^5,7,8 Results from both preliminary small studies indicated that participants experienced significant improvement in overall sexual function at 6 months. In one of the small studies (in Japanese women), sustained efficacy at 12 months posttreatment was reported.⁷ Neither small study included a placebo-control arm, but they did include the use of validated questionnaires.

In the VIVEVE I trial (a multicenter international study), treatment in the active group consisted of a single, 30-minute outpatient procedure that delivered 90 J/cm² of radiofrequency energy at the level just behind the hymenal ring behind the vaginal introitus. The sham-treated group received ≤1 J/cm² of energy with a similar machine tip.⁸

Statistically significant improvements were reported in the arousal and orgasm domains of the validated Female Sexual Function Index (FSFI) for the active-treatment group compared with the sham-treated group. In addition, there were statistically significant differences in the FSFI and the Female Sexual Distress Scale–Revised total scores in favor of active treatment. Participants in the active-treatment arm reported statistically significant improvement in overall sexual satisfaction coupled with lowered overall sexual distress.⁸

These data are provocative, since the Viveve treatment demonstrated superior efficacy compared with the sham treatment, and prior evidence demonstrated that medical device trials employing a sham arm often demonstrate particularly large placebo/sham effects.⁹ A confirmatory randomized, sham-controlled multicenter US-based trial is currently underway. At present, the VIVEVE I trial remains the only published, large-scale, randomized, sham-controlled, blinded study of a radiofrequency-based treatment.

New emerging data support the efficacy and safety of this specific radiofrequency treatment in patients with mild to moderate urinary stress incontinence; further studies confirming these outcomes are anticipated. The Viveve system is approved in many countries for various conditions, including urinary incontinence (1 country), sexual function (17 countries), vaginal laxity (41 countries), and electrocoagulation and hemostasis (4 countries, including the United States).

Laser technology devices

Laser (Light Amplification by Stimulated Emission of Radiation) therapy, which uses a carbon dioxide (CO2), argon, YAG, or erbium energy source, also is currently marketed as a method to improve various gynecologic conditions, including genital pelvic relaxation syndrome, vaginal laxity, GSM, lichen sclerosus, and sexual problems such as dyspareunia and arousal or orgasmic disorders.

The CO2 laser therapy device, such as the MonaLisa Touch (DEKA Laser), appears to be very popular and widely available. It delivers fractional CO2 laser energy to the vaginal wall, creating sequential micro traumas that subsequently undergo a healing reaction; the newly healed area has an improved underlying tissue architecture (but at a superficial level). The laser’s proposed mechanism of action is that it ablates only a minute fraction of the superficial lamina propria; it acts primarily to stimulate rapid healing of the tissue, creating new collagen and elastic fibers. There is no evidence of scarring.¹⁰

Treatment outcomes with laser device therapy

Authors of a 2017 study series of CO2 laser treatments in women with moderate to severe GSM found that 84% of participants experienced significant improvement in sexual function, dyspareunia, and otherwise unspecified sexual issues from pretreatment to 12 to 24 months posttreatment.¹¹ These findings are consistent with several other case series and provide supportive evidence for the efficacy and safety of CO2 laser therapy. This technology may be appropriate for the treatment of GSM.

Laser technology shows excellent promise for the treatment of GSM symptoms by virtue of its superficial mechanism of action. In addition, several trials have demonstrated efficacy and safety in breast cancer patient populations.¹² This is particularly interesting since breast cancer treatments, such as aromatase inhibitors (considered a mainstay of cancer treatment), can cause severe atrophic vaginitis. Breast cancer survivors often avoid minimally absorbed local vaginal hormonal products, and over-the-counter products (moisturizers and lubricants) are not widely accepted. Hence, a nonhormonal treatment for distressing GSM symptoms is welcomed in this population.

Pagano and colleagues recently studied 82 breast cancer survivors in whom treatment with vaginal moisturizers and lubricants failed.¹² Participants underwent 3 laser treatment cycles approximately 30 to 40 days apart; they demonstrated improvements in vaginal dryness, vaginal itchiness, stinging, dyspareunia, and reduced sensitivity.

Microablative fractional CO2 laser may help reestablish a normative vaginal microbiome by altering the prevalence of lactobacillus species and reestablishing a normative postmenopausal vaginal flora.¹³

The tracking and reporting of adverse events associated with laser procedures has been less than optimal. In my personal clinical experience, consequences from both short- and long-term laser treatments have included vaginal canal agglutination, worsening dyspareunia, and constricture causing vaginal hemorrhage.

Cruz and colleagues recently conducted a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy of fractional CO2 laser compared with topical estriol and laser plus estriol for the treatment of vaginal atrophy in 45 postmenopausal women.¹⁴ They found statistically significant differences in dyspareunia, dryness, and burning compared with baseline levels in all 3 treatment groups. Results with the fractional CO2 laser treatment were deemed to be similar to those of the topical estriol and the combined therapy.¹⁴

By contrast, an erbium (Er):YAG laser, such as the IntimaLase (Fotona, LLC) laser, functions by heating the pelvic tissue and collagen within the introitus and vaginal canal.^15,16 When the underlying collagen is heated, the fibers are thought to thicken and shorten, which may result in immediate contracture of the treated tissue. Additionally, this process stimulates the existing collagen to undergo remodeling and it also may cause neocollagen deposition.¹⁵ In a general review of gynecologic procedures, after 1 to 4 treatment sessions (depending on the study), most patients reported improved sexual satisfaction or vaginal tightness.¹⁵

Although trials have included small numbers of patients, early evidence suggests some lasers with reportedly deeper penetration may be useful for treatment of vaginal laxity, but further studies are needed. In smaller studies, the Er:YAG laser has shown efficacy and safety in the treatment of stress urinary incontinence and improved lower urinary tract symptoms, quality of life, and sexual function.^16,17

Insurance does not cover energy-based treatment costs

Currently, both laser and radiofrequency device treatments are considered fee-for-service interventions. Radiofrequency and laser treatments for gynecologic conditions are not covered by health insurance, and treatment costs can be prohibitive for many patients. In addition, the long-term safety of these treatments remains to be studied further, and the optimal time for a repeat procedure has yet to be elucidated.

The FDA cautions against energy-based procedures

In July 2018, the FDA released a statement of concern reiterating the need for research and randomized clinical trials before energy-based device treatments can be widely accepted, and that they are currently cleared only for general gynecologic indications and not for disorders and symptoms related to menopause, urinary incontinence, or sexual function.¹⁸

The FDA stated that “we have not cleared or approved for marketing any energy-based devices to treat these symptoms or conditions [vaginal laxity; vaginal atrophy, dryness, or itching; pain during sexual intercourse; pain during urination; decreased sexual sensation], or any symptoms related to menopause, urinary incontinence, or sexual function.” The FDA noted that serious complications have been reported, including vaginal burns, scarring, pain during sexual intercourse, and recurring, chronic pain. The FDA issued letters to 7 companies regarding concerns about the marketing of their devices for off-label use and promotion.

Several societies have responded. ACOG reaffirmed its 2016 position statement on fractional laser treatment of vulvovaginal atrophy.¹⁹ JoAnn Pinkerton, MD, Executive Director of The North American Menopause Society (NAMS), and Sheryl Kingsberg, PhD, President of NAMS, alerted their members that both health care professionals and consumers should tread cautiously, and they encouraged scrutiny of existing evidence as all energy-based treatments are not created equal.²⁰ They noted that some research does exist and cited 2 randomized, sham-controlled clinical trials that have been published.

Looking forward

Various novel technologic therapies are entering the gynecologic market. ObGyns must critically evaluate these emerging technologies with a keen understanding of their underlying mechanism of action, the level of scientific evidence, and the treatment’s proposed therapeutic value.

Radiofrequency energy devices appear to be better positioned to treat urinary incontinence and vaginal relaxation syndrome because of their capability for deep tissue penetration. Current data show that laser technology has excellent promise for the treatment and management of GSM. Both technologies warrant further investigation in long-term randomized, sham-controlled trials that assess efficacy and safety with validated instruments over an extended period. In addition, should these technologies prove useful in the overall treatment armamentarium for gynecologic conditions, the question of affordability and insurance coverage needs to be addressed.

ObGyns must advocate for female sexual wellness and encourage a comprehensive multidisciplinary team approach for offering various therapies. Ultimately, responsible use of evidence-based innovative technology should be incorporated into the treatment paradigm.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.