Perspectives

Is your 42-year-old patient with well-controlled hypertension and type 2 diabetes dealing with a mood disorder that should be regarded as a psychiatric illness – or is she experiencing demoralization and grief?

In this installment of Mental Health Consult, the patient screens positive for depression but is ambivalent about taking antidepressants. In addition, the patient believes she has a number of coping resources that she can utilize. Finding out whether there is a need for an evidence-based psychotherapy, medication, or if other interventions are appropriate requires four key questions when taking a history.

[email protected]

On Twitter @whitneymcknight

Is your 42-year-old patient with well-controlled hypertension and type 2 diabetes dealing with a mood disorder that should be regarded as a psychiatric illness – or is she experiencing demoralization and grief?

In this installment of Mental Health Consult, the patient screens positive for depression but is ambivalent about taking antidepressants. In addition, the patient believes she has a number of coping resources that she can utilize. Finding out whether there is a need for an evidence-based psychotherapy, medication, or if other interventions are appropriate requires four key questions when taking a history.

[email protected]

On Twitter @whitneymcknight

Is your 42-year-old patient with well-controlled hypertension and type 2 diabetes dealing with a mood disorder that should be regarded as a psychiatric illness – or is she experiencing demoralization and grief?

In this installment of Mental Health Consult, the patient screens positive for depression but is ambivalent about taking antidepressants. In addition, the patient believes she has a number of coping resources that she can utilize. Finding out whether there is a need for an evidence-based psychotherapy, medication, or if other interventions are appropriate requires four key questions when taking a history.

[email protected]

On Twitter @whitneymcknight

When using biologic therapies for psoriasis, it is important to evaluate long-term efficacy (>4 years of follow-up). Biologic drug survival in psoriasis reflects long-term performance in real-life settings. Prior studies have yielded inconsistent results.

Vilarrasa et al (J Am Acad Dermatol. 2016;74:1066-1072) conducted an observational retrospective study called ORBIT (Outcome and Retention Rate of Biologic Treatments for Psoriasis) to determine drug survival (the mean length of time patients remain on a drug) in a cohort of 427 patients (63.5% male; mean age, 50.2 years) with moderate to severe psoriasis vulgaris (mean baseline psoriasis area and severity index [PASI], 16.4). In addition to determining mean drug survival times for etanercept, infliximab, adalimumab, and ustekinumab, investigators searched for variables that positively or negatively affected drug survival times. Data were extracted from clinical records of patients treated with biologic agents over a 4-year period. Drug survival was analyzed using the Kaplan-Meier method and the influence of several covariates was assessed using Cox regression.

The investigators evaluated 703 treatment courses. The overall median drug survival was 31.0 months. Cumulative probability of drug survival was lower in obese patients (23.0 months; 95% CI, 17.4-28.6) than in patients with body mass index less than 30 (37.3 months; 95% CI, 29.4-45.1; P=.001). Drug survival was significantly higher for ustekinumab than for any other biologic agent (log-rank test, P<.001). Multivariate analysis showed that obesity, etanercept treatment, and strict adherence to approved doses were associated with an increased probability of drug withdrawal, whereas ustekinumab treatment and PASI 75 and PASI 90 responses at week 16 prolonged drug survival. Data were collected retrospectively.

What’s the issue?

These results should help to educate patients and to manage expectations about drug efficacy. They should also give guidance to physicians. Patients who respond rapidly to biologics—PASI 70 or PASI 90 clearance during the induction phase—are more likely to enjoy long-term remission. In contrast, those with a high body mass index should be advised that their psoriasis may take longer to respond to treatment and may need combination therapy for optimal clearance.

We want to know your views! Tell us what you think.

When using biologic therapies for psoriasis, it is important to evaluate long-term efficacy (>4 years of follow-up). Biologic drug survival in psoriasis reflects long-term performance in real-life settings. Prior studies have yielded inconsistent results.

Vilarrasa et al (J Am Acad Dermatol. 2016;74:1066-1072) conducted an observational retrospective study called ORBIT (Outcome and Retention Rate of Biologic Treatments for Psoriasis) to determine drug survival (the mean length of time patients remain on a drug) in a cohort of 427 patients (63.5% male; mean age, 50.2 years) with moderate to severe psoriasis vulgaris (mean baseline psoriasis area and severity index [PASI], 16.4). In addition to determining mean drug survival times for etanercept, infliximab, adalimumab, and ustekinumab, investigators searched for variables that positively or negatively affected drug survival times. Data were extracted from clinical records of patients treated with biologic agents over a 4-year period. Drug survival was analyzed using the Kaplan-Meier method and the influence of several covariates was assessed using Cox regression.

The investigators evaluated 703 treatment courses. The overall median drug survival was 31.0 months. Cumulative probability of drug survival was lower in obese patients (23.0 months; 95% CI, 17.4-28.6) than in patients with body mass index less than 30 (37.3 months; 95% CI, 29.4-45.1; P=.001). Drug survival was significantly higher for ustekinumab than for any other biologic agent (log-rank test, P<.001). Multivariate analysis showed that obesity, etanercept treatment, and strict adherence to approved doses were associated with an increased probability of drug withdrawal, whereas ustekinumab treatment and PASI 75 and PASI 90 responses at week 16 prolonged drug survival. Data were collected retrospectively.

What’s the issue?

These results should help to educate patients and to manage expectations about drug efficacy. They should also give guidance to physicians. Patients who respond rapidly to biologics—PASI 70 or PASI 90 clearance during the induction phase—are more likely to enjoy long-term remission. In contrast, those with a high body mass index should be advised that their psoriasis may take longer to respond to treatment and may need combination therapy for optimal clearance.

We want to know your views! Tell us what you think.

When using biologic therapies for psoriasis, it is important to evaluate long-term efficacy (>4 years of follow-up). Biologic drug survival in psoriasis reflects long-term performance in real-life settings. Prior studies have yielded inconsistent results.

Vilarrasa et al (J Am Acad Dermatol. 2016;74:1066-1072) conducted an observational retrospective study called ORBIT (Outcome and Retention Rate of Biologic Treatments for Psoriasis) to determine drug survival (the mean length of time patients remain on a drug) in a cohort of 427 patients (63.5% male; mean age, 50.2 years) with moderate to severe psoriasis vulgaris (mean baseline psoriasis area and severity index [PASI], 16.4). In addition to determining mean drug survival times for etanercept, infliximab, adalimumab, and ustekinumab, investigators searched for variables that positively or negatively affected drug survival times. Data were extracted from clinical records of patients treated with biologic agents over a 4-year period. Drug survival was analyzed using the Kaplan-Meier method and the influence of several covariates was assessed using Cox regression.

The investigators evaluated 703 treatment courses. The overall median drug survival was 31.0 months. Cumulative probability of drug survival was lower in obese patients (23.0 months; 95% CI, 17.4-28.6) than in patients with body mass index less than 30 (37.3 months; 95% CI, 29.4-45.1; P=.001). Drug survival was significantly higher for ustekinumab than for any other biologic agent (log-rank test, P<.001). Multivariate analysis showed that obesity, etanercept treatment, and strict adherence to approved doses were associated with an increased probability of drug withdrawal, whereas ustekinumab treatment and PASI 75 and PASI 90 responses at week 16 prolonged drug survival. Data were collected retrospectively.

What’s the issue?

These results should help to educate patients and to manage expectations about drug efficacy. They should also give guidance to physicians. Patients who respond rapidly to biologics—PASI 70 or PASI 90 clearance during the induction phase—are more likely to enjoy long-term remission. In contrast, those with a high body mass index should be advised that their psoriasis may take longer to respond to treatment and may need combination therapy for optimal clearance.

We want to know your views! Tell us what you think.

A geriatric patient who recently lost his wife presents with significant weight loss and appears disheveled. He speaks of reuniting with his wife as soon as possible. How do you quickly stabilize this patient who appears to be experiencing psychotic depression?

In this installment of Mental Health Consult, our panel members discuss their recommendations for triaging a 65-year-old recently widowed man with a history of prostate cancer but no prior history of psychosis.

Join our panel of experts from George Washington University, Washington, including Katalin Roth, MD, director of geriatrics and palliative medicine; April Barbour, MD, MPH, director of the division of general internal medicine; and Lorenzo Norris, MD, medical director of psychiatric and behavioral services, as they discuss how to effectively deal with a geriatric patient in crisis.

[email protected]

On Twitter @whitneymcknight

A geriatric patient who recently lost his wife presents with significant weight loss and appears disheveled. He speaks of reuniting with his wife as soon as possible. How do you quickly stabilize this patient who appears to be experiencing psychotic depression?

In this installment of Mental Health Consult, our panel members discuss their recommendations for triaging a 65-year-old recently widowed man with a history of prostate cancer but no prior history of psychosis.

Join our panel of experts from George Washington University, Washington, including Katalin Roth, MD, director of geriatrics and palliative medicine; April Barbour, MD, MPH, director of the division of general internal medicine; and Lorenzo Norris, MD, medical director of psychiatric and behavioral services, as they discuss how to effectively deal with a geriatric patient in crisis.

[email protected]

On Twitter @whitneymcknight

A geriatric patient who recently lost his wife presents with significant weight loss and appears disheveled. He speaks of reuniting with his wife as soon as possible. How do you quickly stabilize this patient who appears to be experiencing psychotic depression?

In this installment of Mental Health Consult, our panel members discuss their recommendations for triaging a 65-year-old recently widowed man with a history of prostate cancer but no prior history of psychosis.

Join our panel of experts from George Washington University, Washington, including Katalin Roth, MD, director of geriatrics and palliative medicine; April Barbour, MD, MPH, director of the division of general internal medicine; and Lorenzo Norris, MD, medical director of psychiatric and behavioral services, as they discuss how to effectively deal with a geriatric patient in crisis.

[email protected]

On Twitter @whitneymcknight

In 1978, when England’s Louise Brown became the world’s first baby born through in vitro fertilization, physicians at academic centers all over the United States scrambled to figure out how they, too, could provide IVF to the thousands of infertile couples for whom nothing else had worked.

Interest in IVF was strong even before British physiologist Robert Edwards and gynecologist Patrick Steptoe announced their success. “We knew that IVF was being developed, that it had been accomplished in animals, and ultimately we knew it was going to succeed in humans,” said reproductive endocrinologist Zev Rosenwaks, MD, of the Weill Cornell Center for Reproductive Medicine in New York.

In the late 1970s, “we were able to help only about two-thirds of couples with infertility, either with tubal surgery, insemination – often with donor sperm – or ovulation induction. A full third could not be helped. We predicted that IVF would allow us to treat virtually everyone,” Dr. Rosenwaks said.

But even after the first IVF birth, information on the revolutionary procedure remained frustratingly scarce.

“Edwards and Steptoe would talk to nobody,” said Richard Marrs, MD, a reproductive endocrinologist and infertility specialist in Los Angeles.

And federal research support for “test-tube babies,” as IVF was known in the media then, was nil thanks to a ban on government-funded human embryo research that persists to this day.

The U.S. physicians who took part in the rush to achieve an IVF birth – most of them young fellows at the time – recall a period of improvisation, collaboration, shoestring budgets, and surprise findings.

“People who just started 10 or even 20 years ago don’t realize what it took for us to learn how to go about doing IVF,” said Dr. Rosenwaks, who in the first years of IVF worked closely with Dr. Howard Jones and Dr. Georgeanna Jones, the first team in the U.S. to announce an IVF baby.

Labs in closets

In the late 1970s, Dr. Marrs, then a fellow at the University of Southern California, was focused on surgical methods to treat infertility – and demand was sky-high. Intrauterine devices used in the 1970s left many women with severe scarring and inflammation of the fallopian tubes.

“I was very surgically oriented,” Dr. Marrs said. “I thought I could fix any disaster in the pelvis that was put in front of me, especially with microsurgery.”

After the news of IVF success in England, Dr. Marrs threw himself into a side project at a nearby cancer center, working on single-cell cultures. “I thought if I could grow tumor cells, I could one day grow embryos,” he said.

A year later, Dr. Marrs set up the first IVF lab at USC – in a storage closet. “I sterilized the place and that was our first IVF lab, literally a closet with an incubator and a microscope.” Its budget was accordingly thin, as the director at the time felt certain that IVF was a dead end. To fund his work, Dr. Marrs asked IVF candidate patients for research donations in lieu of payment.

But before Dr. Marrs attempted to perform his first IVF, two centers in Australia announced their own IVF babies. “I decided I really needed to go see someone who had had a baby,” he said. He used his vacation time to fly to Melbourne, shuttling between two competing clinics that were “four blocks apart and wouldn’t even talk to each other,” he recalled.

Over 6 weeks, “I learned how to stimulate, how to time ovulation. I watched the PhDs in the lab – how they handled the eggs and the sperm, what the conditions were, the incubator settings,” he said.

The first IVF babies in the United States were born only months apart: The first, in December 1981, was at the Jones Institute for Reproductive Medicine in Norfolk, Va., where Dr. Rosenwaks served as the first director.

The second baby born was at USC. After that, “we had 4,000 women on a waiting list, all under age 35,” Dr. Marrs said. The Jones Institute reportedly had 5,000.

As demand soared and more IVF babies arrived, the cloak of secrecy surrounding the procedure started to lift. British, Australian, and U.S. clinicians started getting together regularly. “We would pick a spot in the world, present our data: what we’d done, how many cycles, what we used for stimulation, when we took the eggs out,” Dr. Marrs said. “I don’t know how many hundreds of thousands of miles I flew in the first years of IVF, because it was the only way I could get information. We would literally stay up all night talking.”

Answering safety questions

Alan H. DeCherney, MD, currently an infertility researcher at the National Institutes of Health, started Yale University’s IVF program at around the same time Dr. Marrs and the Joneses were starting theirs. Yale already had a large infertility practice, and only academic centers had the laboratory resources and skilled staff needed to attempt IVF in those years.

In 1983, when Yale announced the birth of its first IVF baby – the fifth in the United States – Dr. DeCherney was starting to think about measuring outcomes, as there was concern over the potential for congenital anomalies related to IVF. “This was such a change in the way conception occurred, people were afraid that all kinds of crazy things would happen,” he said.

One concern was about ovarian stimulation with fertility drugs or gonadotropins. The earliest efforts – including by Dr. Steptoe and Dr. Edwards – used no drugs, instead trying to pinpoint the moment of natural egg release by measuring a woman’s hormone levels constantly, but these proved disappointing. Use of clomiphene citrate and human menopausal gonadotropin allowed for more control over timing, and for multiple mature eggs to be harvested at once.

But there were still many unanswered questions related to these agents’ safety and dosing, both for women and for babies.

When the NIH refused to fund a study of IVF outcomes, Dr. DeCherney and Dr. Marrs collaborated on a registry funded by a gonadotropin maker. “The drug company didn’t want to be associated with some terrible abnormal outcomes,” Dr. DeCherney recalled, though by then, “there were 10, maybe even 20 babies around the world, and they seemed to be fine,” he said.

The first registry results affirmed no changes in the rate of congenital abnormalities. (Larger, more recent studies have shown a small but significant elevation in birth defect risk associated with IVF.) A few years later, ovarian stimulation was adjusted to correspond with ovarian reserve, reducing the risk of ovarian hyperstimulation syndrome.

But even by the late 1980s, success rates for IVF per attempted cycle were still low overall, leading many critics, even within the profession, to accuse practitioners of misleading couples. Charles E. Miller, MD, an infertility specialist in Chicago, recalled an early investigation by a major newspaper “that looked at all the IVF clinics in Chicago and found the chances of having a baby was under 3%.”

It was true, Dr. Miller acknowledged – “the rates were dismal. But remember that IVF at the time was still considered a procedure of last resort.” Complex diagnostic testing to determine the cause of infertility, surgery, and fertility drugs all came first.

Some important innovations would soon change that and turn IVF into a mainstay of infertility treatment that could help women not only with damaged tubes but also with ovarian failure, low ovarian reserve, or dense pelvic adhesions. Even some types of male factor infertility would find an answer in IVF, by way of intracytoplasmic sperm transfer.

Eggs without surgery

Laparoscopic egg retrieval was the norm in the first decade of IVF. “We went through the belly button, allowing us to directly visualize the ovary and see whether ovulation had already occurred or we had to retrieve it by introducing a needle into the follicle,” Dr. Rosenwaks recalled.

“Some of us were doing 6 or even 10 laparoscopies a day, and it was physically quite challenging,” he said. “There were no video screens in those days. You had to bend over the scope.” And it was worse still for patients, who had to endure multiple surgeries.

Though egg and embryo cryopreservation were already being worked on, it would be years before these techniques were optimized, giving women more chances from a single retrieval of oocytes.

Finding a less invasive means of retrieving eggs was crucial.

Maria Bustillo, MD, an infertility specialist in Miami, recalled being criticized by peers when she and her then-colleagues at the Genetics & IVF Institute in Fairfax, Va., began retrieving eggs via a needle placed in the vagina, using abdominal ultrasound as a guide.

While the technique was far less invasive than laparoscopy, “we were doing it semi-blindly, and were told it was dangerous,” Dr. Bustillo said.

But these freehand ultrasound retrievals paved the way for what would become a revolutionary advance – the vaginal ultrasound probe, which by the end of the 1980s made nonsurgical extraction of eggs the norm.

Dr. Marrs recalled receiving a prototype of a vaginal ultrasound probe, in the mid-1980s, and finding patients unwilling to use it, except one who relented only because she had an empty bladder. Abdominal ultrasonography required a full bladder to work.

“It was as though somebody had removed the cloud cover,” he said. “I couldn’t believe it. I could see everything: her ovaries, tiny follicles, the uterus.”

Later probes were fitted with a needle and aspirator to retrieve eggs. Multiple IVF cycles no longer meant multiple surgeries, and the less-invasive procedure helped in recruiting egg donors, allowing women with ovarian disease or low ovarian reserves, including older women, to receive IVF.

“It didn’t make sense for a volunteer to go through a surgery, especially back in the early ’80s when the results were not all that great,” Dr. Bustillo said.

Improving ‘home brews’

The culture media in which embryos were grown was another strong factor limiting the success rates of early IVF. James Toner, MD, PhD, an IVF specialist in Atlanta, called the early media “home brews.”

“Everyone made them themselves,” said Dr. Toner, who spent 15 years at the Jones Institute. “You had to do a hamster or mouse embryo test on every batch to make sure embryos would grow.” And often they did not.

Poor success rates resulted in the emergence of alternative procedures: GIFT (gamete intrafallopian transfer) and ZIFT (zygote intrafallopian transfer). Both aimed to get embryos back into the patient as soon as possible, with the thought that the natural environment offered a better chance for success.

But advances in culture media allowed more time for embryos to be observed. With longer development, “you could do a better job selecting the ones that had a chance, and de-selecting those with no chance,” Dr. Toner said.

This also meant fewer embryos could be transferred back into patients, lowering the likelihood of multiples. Ultimately, for young women, single-embryo transfer would become the norm. “The problem of multiple pregnancy that we used to have no longer exists for IVF,” Dr. Toner said.

Allowing embryos to reach the blastocyst stage – day 5 or 6 – opened other, previously unthinkable possibilities: placing embryos directly into the uterus, without surgery, and pre-implementation genetic screening for abnormalities.

“As the cell number went up, the idea that you could do a genetic test with minimal impact on the embryo eventually became true,” Dr. Toner said.

A genetic revolution?

While many important IVF innovations were achieved in countries with staunch government support, one of the remarkable things about IVF’s evolution in the United States is that so many occurred with virtually none.

By the mid-1990s, most of the early practitioners had moved from academic settings into private practice, though they continued to publish. “After a while it didn’t help to be in academics. It just sort of slowed you down. Because you weren’t going to get any [government] money anyway, you might as well be in a place that’s a little more nimble,” Dr. Toner said.

At the same time, he said, IVF remains a costly, usually unreimbursed procedure – limiting patients’ willingness to take part in randomized trials. “IVF research is built more on cohort studies.”

Most of the current research focus in IVF is on possibilities for genetic screening. Dr. Miller said that rapid DNA sequencing is allowing specialists to “look at more, pick up more abnormalities. That will continue to improve so that we will be able to see virtually everything.”

But he cautioned there is still much to be done in IVF apart from the genetics – he’s concerned, he said, that the field has moved too far from its surgical origins, and is working with the academic societies to encourage more surgical training.

“We don’t do the same work we did before on fallopian tubes, which is good,” Dr. Miller said, noting that there have been many advances, particularly minimally invasive surgeries in the uterus or ovaries, that have occurred parallel to IVF and can improve success rates. “I think we have a better understanding of what kind of patients require surgical treatments and what kind of surgeries can help enhance fertility, and also what not to do.”

Dr. Bustillo said that “cytogenetics is wonderful, but not everything. You have embryos that are genetically normal and still don’t implant. There’s a lot of work to be done on the interaction between the mother and the embryo.”

Dr. Marrs said that even safety questions related to stimulation have yet to be fully answered. “I’ve always been a big believer that lower is better, but we need to know whether stimulation creates genetic abnormalities and whether less stimulation produces fewer – and we need more data to prove it,” he said. Dr. Marrs is an investigator on a national randomized trial comparing outcomes from IVF with standard-dose and ultra-low dose stimulation.

Access, income, and age

The IVF pioneers agree broadly that access to IVF is nowhere near what it should be in the United States, where only 15 states mandate any insurance coverage for infertility.

“Our limited access to care is a crime,” Dr. Toner said. “People who, through no fault of their own, find themselves infertile are asked to write a check for $15,000 to get pregnant. That’s not fair.”

Dr. DeCherney called access “an ethical issue, because who gets IVF? People with higher incomes. And if IVF allows you to select better embryos – whatever that means – it gives that group another advantage.”

Dr. Toner warned that the push toward genetic testing of embryos, especially in the absence of known hereditary disease, could create new problems for the profession – not unlike in the early days of IVF, when the Jones Institute and other clinics were picketed over the specter of “test tube babies.”

“It’s one thing to say this embryo does not have the right number of chromosomes and couldn’t possibly be a child, so let’s not use it, but what about looking for traits? Sex selection? We have this privileged position in which the government does not really interfere in what we do, but to retain this status we need to stay within the bounds that our society accepts,” Dr. Toner said.

In recent years, IVF uptake has been high among women of advanced reproductive age, which poses its own set of challenges. Outcomes in older women using their own eggs become progressively poorer with age, though donor eggs drastically improve their chances, and egg freezing offers the possibility of preserving quality eggs for later pregnancies.

“We could make this situation better by promoting social freezing, doing more work for women early in their lives to get out their own eggs and store them,” Dr. Miller said. “But again, you still face the issue of access.”

Regardless of what technologies are available or become available in assisted reproduction, doctors and women alike need to be better educated on their options and chances early, with a clearer understanding of what happens as they age, Dr. Bustillo said.

“This is not to pressure them, but just so they understand that when they get to be 42 and are just thinking about reproducing, it’s not a major surprise when I tell them this could be a problem,” she said.

Throughout 2016, Ob.Gyn. News is celebrating its 50th anniversary with exclusive articles looking at the evolution of the specialty, including the history of contraception, changes in gynecologic surgery, and the transformation of the well-woman visit.

In 1978, when England’s Louise Brown became the world’s first baby born through in vitro fertilization, physicians at academic centers all over the United States scrambled to figure out how they, too, could provide IVF to the thousands of infertile couples for whom nothing else had worked.

Interest in IVF was strong even before British physiologist Robert Edwards and gynecologist Patrick Steptoe announced their success. “We knew that IVF was being developed, that it had been accomplished in animals, and ultimately we knew it was going to succeed in humans,” said reproductive endocrinologist Zev Rosenwaks, MD, of the Weill Cornell Center for Reproductive Medicine in New York.

In the late 1970s, “we were able to help only about two-thirds of couples with infertility, either with tubal surgery, insemination – often with donor sperm – or ovulation induction. A full third could not be helped. We predicted that IVF would allow us to treat virtually everyone,” Dr. Rosenwaks said.

But even after the first IVF birth, information on the revolutionary procedure remained frustratingly scarce.

“Edwards and Steptoe would talk to nobody,” said Richard Marrs, MD, a reproductive endocrinologist and infertility specialist in Los Angeles.

And federal research support for “test-tube babies,” as IVF was known in the media then, was nil thanks to a ban on government-funded human embryo research that persists to this day.

The U.S. physicians who took part in the rush to achieve an IVF birth – most of them young fellows at the time – recall a period of improvisation, collaboration, shoestring budgets, and surprise findings.

“People who just started 10 or even 20 years ago don’t realize what it took for us to learn how to go about doing IVF,” said Dr. Rosenwaks, who in the first years of IVF worked closely with Dr. Howard Jones and Dr. Georgeanna Jones, the first team in the U.S. to announce an IVF baby.

Labs in closets

In the late 1970s, Dr. Marrs, then a fellow at the University of Southern California, was focused on surgical methods to treat infertility – and demand was sky-high. Intrauterine devices used in the 1970s left many women with severe scarring and inflammation of the fallopian tubes.

“I was very surgically oriented,” Dr. Marrs said. “I thought I could fix any disaster in the pelvis that was put in front of me, especially with microsurgery.”

After the news of IVF success in England, Dr. Marrs threw himself into a side project at a nearby cancer center, working on single-cell cultures. “I thought if I could grow tumor cells, I could one day grow embryos,” he said.

A year later, Dr. Marrs set up the first IVF lab at USC – in a storage closet. “I sterilized the place and that was our first IVF lab, literally a closet with an incubator and a microscope.” Its budget was accordingly thin, as the director at the time felt certain that IVF was a dead end. To fund his work, Dr. Marrs asked IVF candidate patients for research donations in lieu of payment.

But before Dr. Marrs attempted to perform his first IVF, two centers in Australia announced their own IVF babies. “I decided I really needed to go see someone who had had a baby,” he said. He used his vacation time to fly to Melbourne, shuttling between two competing clinics that were “four blocks apart and wouldn’t even talk to each other,” he recalled.

Over 6 weeks, “I learned how to stimulate, how to time ovulation. I watched the PhDs in the lab – how they handled the eggs and the sperm, what the conditions were, the incubator settings,” he said.

The first IVF babies in the United States were born only months apart: The first, in December 1981, was at the Jones Institute for Reproductive Medicine in Norfolk, Va., where Dr. Rosenwaks served as the first director.

The second baby born was at USC. After that, “we had 4,000 women on a waiting list, all under age 35,” Dr. Marrs said. The Jones Institute reportedly had 5,000.

As demand soared and more IVF babies arrived, the cloak of secrecy surrounding the procedure started to lift. British, Australian, and U.S. clinicians started getting together regularly. “We would pick a spot in the world, present our data: what we’d done, how many cycles, what we used for stimulation, when we took the eggs out,” Dr. Marrs said. “I don’t know how many hundreds of thousands of miles I flew in the first years of IVF, because it was the only way I could get information. We would literally stay up all night talking.”

Answering safety questions

Alan H. DeCherney, MD, currently an infertility researcher at the National Institutes of Health, started Yale University’s IVF program at around the same time Dr. Marrs and the Joneses were starting theirs. Yale already had a large infertility practice, and only academic centers had the laboratory resources and skilled staff needed to attempt IVF in those years.

In 1983, when Yale announced the birth of its first IVF baby – the fifth in the United States – Dr. DeCherney was starting to think about measuring outcomes, as there was concern over the potential for congenital anomalies related to IVF. “This was such a change in the way conception occurred, people were afraid that all kinds of crazy things would happen,” he said.

One concern was about ovarian stimulation with fertility drugs or gonadotropins. The earliest efforts – including by Dr. Steptoe and Dr. Edwards – used no drugs, instead trying to pinpoint the moment of natural egg release by measuring a woman’s hormone levels constantly, but these proved disappointing. Use of clomiphene citrate and human menopausal gonadotropin allowed for more control over timing, and for multiple mature eggs to be harvested at once.

But there were still many unanswered questions related to these agents’ safety and dosing, both for women and for babies.

When the NIH refused to fund a study of IVF outcomes, Dr. DeCherney and Dr. Marrs collaborated on a registry funded by a gonadotropin maker. “The drug company didn’t want to be associated with some terrible abnormal outcomes,” Dr. DeCherney recalled, though by then, “there were 10, maybe even 20 babies around the world, and they seemed to be fine,” he said.

The first registry results affirmed no changes in the rate of congenital abnormalities. (Larger, more recent studies have shown a small but significant elevation in birth defect risk associated with IVF.) A few years later, ovarian stimulation was adjusted to correspond with ovarian reserve, reducing the risk of ovarian hyperstimulation syndrome.

But even by the late 1980s, success rates for IVF per attempted cycle were still low overall, leading many critics, even within the profession, to accuse practitioners of misleading couples. Charles E. Miller, MD, an infertility specialist in Chicago, recalled an early investigation by a major newspaper “that looked at all the IVF clinics in Chicago and found the chances of having a baby was under 3%.”

It was true, Dr. Miller acknowledged – “the rates were dismal. But remember that IVF at the time was still considered a procedure of last resort.” Complex diagnostic testing to determine the cause of infertility, surgery, and fertility drugs all came first.

Some important innovations would soon change that and turn IVF into a mainstay of infertility treatment that could help women not only with damaged tubes but also with ovarian failure, low ovarian reserve, or dense pelvic adhesions. Even some types of male factor infertility would find an answer in IVF, by way of intracytoplasmic sperm transfer.

Eggs without surgery

Laparoscopic egg retrieval was the norm in the first decade of IVF. “We went through the belly button, allowing us to directly visualize the ovary and see whether ovulation had already occurred or we had to retrieve it by introducing a needle into the follicle,” Dr. Rosenwaks recalled.

“Some of us were doing 6 or even 10 laparoscopies a day, and it was physically quite challenging,” he said. “There were no video screens in those days. You had to bend over the scope.” And it was worse still for patients, who had to endure multiple surgeries.

Though egg and embryo cryopreservation were already being worked on, it would be years before these techniques were optimized, giving women more chances from a single retrieval of oocytes.

Finding a less invasive means of retrieving eggs was crucial.

Maria Bustillo, MD, an infertility specialist in Miami, recalled being criticized by peers when she and her then-colleagues at the Genetics & IVF Institute in Fairfax, Va., began retrieving eggs via a needle placed in the vagina, using abdominal ultrasound as a guide.

While the technique was far less invasive than laparoscopy, “we were doing it semi-blindly, and were told it was dangerous,” Dr. Bustillo said.

But these freehand ultrasound retrievals paved the way for what would become a revolutionary advance – the vaginal ultrasound probe, which by the end of the 1980s made nonsurgical extraction of eggs the norm.

Dr. Marrs recalled receiving a prototype of a vaginal ultrasound probe, in the mid-1980s, and finding patients unwilling to use it, except one who relented only because she had an empty bladder. Abdominal ultrasonography required a full bladder to work.

“It was as though somebody had removed the cloud cover,” he said. “I couldn’t believe it. I could see everything: her ovaries, tiny follicles, the uterus.”

Later probes were fitted with a needle and aspirator to retrieve eggs. Multiple IVF cycles no longer meant multiple surgeries, and the less-invasive procedure helped in recruiting egg donors, allowing women with ovarian disease or low ovarian reserves, including older women, to receive IVF.

“It didn’t make sense for a volunteer to go through a surgery, especially back in the early ’80s when the results were not all that great,” Dr. Bustillo said.

Improving ‘home brews’

The culture media in which embryos were grown was another strong factor limiting the success rates of early IVF. James Toner, MD, PhD, an IVF specialist in Atlanta, called the early media “home brews.”

“Everyone made them themselves,” said Dr. Toner, who spent 15 years at the Jones Institute. “You had to do a hamster or mouse embryo test on every batch to make sure embryos would grow.” And often they did not.

Poor success rates resulted in the emergence of alternative procedures: GIFT (gamete intrafallopian transfer) and ZIFT (zygote intrafallopian transfer). Both aimed to get embryos back into the patient as soon as possible, with the thought that the natural environment offered a better chance for success.

But advances in culture media allowed more time for embryos to be observed. With longer development, “you could do a better job selecting the ones that had a chance, and de-selecting those with no chance,” Dr. Toner said.

This also meant fewer embryos could be transferred back into patients, lowering the likelihood of multiples. Ultimately, for young women, single-embryo transfer would become the norm. “The problem of multiple pregnancy that we used to have no longer exists for IVF,” Dr. Toner said.

Allowing embryos to reach the blastocyst stage – day 5 or 6 – opened other, previously unthinkable possibilities: placing embryos directly into the uterus, without surgery, and pre-implementation genetic screening for abnormalities.

“As the cell number went up, the idea that you could do a genetic test with minimal impact on the embryo eventually became true,” Dr. Toner said.

A genetic revolution?

While many important IVF innovations were achieved in countries with staunch government support, one of the remarkable things about IVF’s evolution in the United States is that so many occurred with virtually none.

By the mid-1990s, most of the early practitioners had moved from academic settings into private practice, though they continued to publish. “After a while it didn’t help to be in academics. It just sort of slowed you down. Because you weren’t going to get any [government] money anyway, you might as well be in a place that’s a little more nimble,” Dr. Toner said.

At the same time, he said, IVF remains a costly, usually unreimbursed procedure – limiting patients’ willingness to take part in randomized trials. “IVF research is built more on cohort studies.”

Most of the current research focus in IVF is on possibilities for genetic screening. Dr. Miller said that rapid DNA sequencing is allowing specialists to “look at more, pick up more abnormalities. That will continue to improve so that we will be able to see virtually everything.”

But he cautioned there is still much to be done in IVF apart from the genetics – he’s concerned, he said, that the field has moved too far from its surgical origins, and is working with the academic societies to encourage more surgical training.

“We don’t do the same work we did before on fallopian tubes, which is good,” Dr. Miller said, noting that there have been many advances, particularly minimally invasive surgeries in the uterus or ovaries, that have occurred parallel to IVF and can improve success rates. “I think we have a better understanding of what kind of patients require surgical treatments and what kind of surgeries can help enhance fertility, and also what not to do.”

Dr. Bustillo said that “cytogenetics is wonderful, but not everything. You have embryos that are genetically normal and still don’t implant. There’s a lot of work to be done on the interaction between the mother and the embryo.”

Dr. Marrs said that even safety questions related to stimulation have yet to be fully answered. “I’ve always been a big believer that lower is better, but we need to know whether stimulation creates genetic abnormalities and whether less stimulation produces fewer – and we need more data to prove it,” he said. Dr. Marrs is an investigator on a national randomized trial comparing outcomes from IVF with standard-dose and ultra-low dose stimulation.

Access, income, and age

The IVF pioneers agree broadly that access to IVF is nowhere near what it should be in the United States, where only 15 states mandate any insurance coverage for infertility.

“Our limited access to care is a crime,” Dr. Toner said. “People who, through no fault of their own, find themselves infertile are asked to write a check for $15,000 to get pregnant. That’s not fair.”

Dr. DeCherney called access “an ethical issue, because who gets IVF? People with higher incomes. And if IVF allows you to select better embryos – whatever that means – it gives that group another advantage.”

Dr. Toner warned that the push toward genetic testing of embryos, especially in the absence of known hereditary disease, could create new problems for the profession – not unlike in the early days of IVF, when the Jones Institute and other clinics were picketed over the specter of “test tube babies.”

“It’s one thing to say this embryo does not have the right number of chromosomes and couldn’t possibly be a child, so let’s not use it, but what about looking for traits? Sex selection? We have this privileged position in which the government does not really interfere in what we do, but to retain this status we need to stay within the bounds that our society accepts,” Dr. Toner said.

In recent years, IVF uptake has been high among women of advanced reproductive age, which poses its own set of challenges. Outcomes in older women using their own eggs become progressively poorer with age, though donor eggs drastically improve their chances, and egg freezing offers the possibility of preserving quality eggs for later pregnancies.

“We could make this situation better by promoting social freezing, doing more work for women early in their lives to get out their own eggs and store them,” Dr. Miller said. “But again, you still face the issue of access.”

Regardless of what technologies are available or become available in assisted reproduction, doctors and women alike need to be better educated on their options and chances early, with a clearer understanding of what happens as they age, Dr. Bustillo said.

“This is not to pressure them, but just so they understand that when they get to be 42 and are just thinking about reproducing, it’s not a major surprise when I tell them this could be a problem,” she said.

Throughout 2016, Ob.Gyn. News is celebrating its 50th anniversary with exclusive articles looking at the evolution of the specialty, including the history of contraception, changes in gynecologic surgery, and the transformation of the well-woman visit.

In 1978, when England’s Louise Brown became the world’s first baby born through in vitro fertilization, physicians at academic centers all over the United States scrambled to figure out how they, too, could provide IVF to the thousands of infertile couples for whom nothing else had worked.

Interest in IVF was strong even before British physiologist Robert Edwards and gynecologist Patrick Steptoe announced their success. “We knew that IVF was being developed, that it had been accomplished in animals, and ultimately we knew it was going to succeed in humans,” said reproductive endocrinologist Zev Rosenwaks, MD, of the Weill Cornell Center for Reproductive Medicine in New York.

In the late 1970s, “we were able to help only about two-thirds of couples with infertility, either with tubal surgery, insemination – often with donor sperm – or ovulation induction. A full third could not be helped. We predicted that IVF would allow us to treat virtually everyone,” Dr. Rosenwaks said.

But even after the first IVF birth, information on the revolutionary procedure remained frustratingly scarce.

“Edwards and Steptoe would talk to nobody,” said Richard Marrs, MD, a reproductive endocrinologist and infertility specialist in Los Angeles.

And federal research support for “test-tube babies,” as IVF was known in the media then, was nil thanks to a ban on government-funded human embryo research that persists to this day.

The U.S. physicians who took part in the rush to achieve an IVF birth – most of them young fellows at the time – recall a period of improvisation, collaboration, shoestring budgets, and surprise findings.

“People who just started 10 or even 20 years ago don’t realize what it took for us to learn how to go about doing IVF,” said Dr. Rosenwaks, who in the first years of IVF worked closely with Dr. Howard Jones and Dr. Georgeanna Jones, the first team in the U.S. to announce an IVF baby.

Labs in closets

In the late 1970s, Dr. Marrs, then a fellow at the University of Southern California, was focused on surgical methods to treat infertility – and demand was sky-high. Intrauterine devices used in the 1970s left many women with severe scarring and inflammation of the fallopian tubes.

“I was very surgically oriented,” Dr. Marrs said. “I thought I could fix any disaster in the pelvis that was put in front of me, especially with microsurgery.”

After the news of IVF success in England, Dr. Marrs threw himself into a side project at a nearby cancer center, working on single-cell cultures. “I thought if I could grow tumor cells, I could one day grow embryos,” he said.

A year later, Dr. Marrs set up the first IVF lab at USC – in a storage closet. “I sterilized the place and that was our first IVF lab, literally a closet with an incubator and a microscope.” Its budget was accordingly thin, as the director at the time felt certain that IVF was a dead end. To fund his work, Dr. Marrs asked IVF candidate patients for research donations in lieu of payment.

But before Dr. Marrs attempted to perform his first IVF, two centers in Australia announced their own IVF babies. “I decided I really needed to go see someone who had had a baby,” he said. He used his vacation time to fly to Melbourne, shuttling between two competing clinics that were “four blocks apart and wouldn’t even talk to each other,” he recalled.

Over 6 weeks, “I learned how to stimulate, how to time ovulation. I watched the PhDs in the lab – how they handled the eggs and the sperm, what the conditions were, the incubator settings,” he said.

The first IVF babies in the United States were born only months apart: The first, in December 1981, was at the Jones Institute for Reproductive Medicine in Norfolk, Va., where Dr. Rosenwaks served as the first director.

The second baby born was at USC. After that, “we had 4,000 women on a waiting list, all under age 35,” Dr. Marrs said. The Jones Institute reportedly had 5,000.

As demand soared and more IVF babies arrived, the cloak of secrecy surrounding the procedure started to lift. British, Australian, and U.S. clinicians started getting together regularly. “We would pick a spot in the world, present our data: what we’d done, how many cycles, what we used for stimulation, when we took the eggs out,” Dr. Marrs said. “I don’t know how many hundreds of thousands of miles I flew in the first years of IVF, because it was the only way I could get information. We would literally stay up all night talking.”

Answering safety questions

Alan H. DeCherney, MD, currently an infertility researcher at the National Institutes of Health, started Yale University’s IVF program at around the same time Dr. Marrs and the Joneses were starting theirs. Yale already had a large infertility practice, and only academic centers had the laboratory resources and skilled staff needed to attempt IVF in those years.

In 1983, when Yale announced the birth of its first IVF baby – the fifth in the United States – Dr. DeCherney was starting to think about measuring outcomes, as there was concern over the potential for congenital anomalies related to IVF. “This was such a change in the way conception occurred, people were afraid that all kinds of crazy things would happen,” he said.

One concern was about ovarian stimulation with fertility drugs or gonadotropins. The earliest efforts – including by Dr. Steptoe and Dr. Edwards – used no drugs, instead trying to pinpoint the moment of natural egg release by measuring a woman’s hormone levels constantly, but these proved disappointing. Use of clomiphene citrate and human menopausal gonadotropin allowed for more control over timing, and for multiple mature eggs to be harvested at once.

But there were still many unanswered questions related to these agents’ safety and dosing, both for women and for babies.

When the NIH refused to fund a study of IVF outcomes, Dr. DeCherney and Dr. Marrs collaborated on a registry funded by a gonadotropin maker. “The drug company didn’t want to be associated with some terrible abnormal outcomes,” Dr. DeCherney recalled, though by then, “there were 10, maybe even 20 babies around the world, and they seemed to be fine,” he said.

The first registry results affirmed no changes in the rate of congenital abnormalities. (Larger, more recent studies have shown a small but significant elevation in birth defect risk associated with IVF.) A few years later, ovarian stimulation was adjusted to correspond with ovarian reserve, reducing the risk of ovarian hyperstimulation syndrome.

But even by the late 1980s, success rates for IVF per attempted cycle were still low overall, leading many critics, even within the profession, to accuse practitioners of misleading couples. Charles E. Miller, MD, an infertility specialist in Chicago, recalled an early investigation by a major newspaper “that looked at all the IVF clinics in Chicago and found the chances of having a baby was under 3%.”

It was true, Dr. Miller acknowledged – “the rates were dismal. But remember that IVF at the time was still considered a procedure of last resort.” Complex diagnostic testing to determine the cause of infertility, surgery, and fertility drugs all came first.

Some important innovations would soon change that and turn IVF into a mainstay of infertility treatment that could help women not only with damaged tubes but also with ovarian failure, low ovarian reserve, or dense pelvic adhesions. Even some types of male factor infertility would find an answer in IVF, by way of intracytoplasmic sperm transfer.

Eggs without surgery

Laparoscopic egg retrieval was the norm in the first decade of IVF. “We went through the belly button, allowing us to directly visualize the ovary and see whether ovulation had already occurred or we had to retrieve it by introducing a needle into the follicle,” Dr. Rosenwaks recalled.

“Some of us were doing 6 or even 10 laparoscopies a day, and it was physically quite challenging,” he said. “There were no video screens in those days. You had to bend over the scope.” And it was worse still for patients, who had to endure multiple surgeries.

Though egg and embryo cryopreservation were already being worked on, it would be years before these techniques were optimized, giving women more chances from a single retrieval of oocytes.

Finding a less invasive means of retrieving eggs was crucial.

Maria Bustillo, MD, an infertility specialist in Miami, recalled being criticized by peers when she and her then-colleagues at the Genetics & IVF Institute in Fairfax, Va., began retrieving eggs via a needle placed in the vagina, using abdominal ultrasound as a guide.

While the technique was far less invasive than laparoscopy, “we were doing it semi-blindly, and were told it was dangerous,” Dr. Bustillo said.

But these freehand ultrasound retrievals paved the way for what would become a revolutionary advance – the vaginal ultrasound probe, which by the end of the 1980s made nonsurgical extraction of eggs the norm.

Dr. Marrs recalled receiving a prototype of a vaginal ultrasound probe, in the mid-1980s, and finding patients unwilling to use it, except one who relented only because she had an empty bladder. Abdominal ultrasonography required a full bladder to work.

“It was as though somebody had removed the cloud cover,” he said. “I couldn’t believe it. I could see everything: her ovaries, tiny follicles, the uterus.”

Later probes were fitted with a needle and aspirator to retrieve eggs. Multiple IVF cycles no longer meant multiple surgeries, and the less-invasive procedure helped in recruiting egg donors, allowing women with ovarian disease or low ovarian reserves, including older women, to receive IVF.

“It didn’t make sense for a volunteer to go through a surgery, especially back in the early ’80s when the results were not all that great,” Dr. Bustillo said.

Improving ‘home brews’

The culture media in which embryos were grown was another strong factor limiting the success rates of early IVF. James Toner, MD, PhD, an IVF specialist in Atlanta, called the early media “home brews.”

“Everyone made them themselves,” said Dr. Toner, who spent 15 years at the Jones Institute. “You had to do a hamster or mouse embryo test on every batch to make sure embryos would grow.” And often they did not.

Poor success rates resulted in the emergence of alternative procedures: GIFT (gamete intrafallopian transfer) and ZIFT (zygote intrafallopian transfer). Both aimed to get embryos back into the patient as soon as possible, with the thought that the natural environment offered a better chance for success.

But advances in culture media allowed more time for embryos to be observed. With longer development, “you could do a better job selecting the ones that had a chance, and de-selecting those with no chance,” Dr. Toner said.

This also meant fewer embryos could be transferred back into patients, lowering the likelihood of multiples. Ultimately, for young women, single-embryo transfer would become the norm. “The problem of multiple pregnancy that we used to have no longer exists for IVF,” Dr. Toner said.

Allowing embryos to reach the blastocyst stage – day 5 or 6 – opened other, previously unthinkable possibilities: placing embryos directly into the uterus, without surgery, and pre-implementation genetic screening for abnormalities.

“As the cell number went up, the idea that you could do a genetic test with minimal impact on the embryo eventually became true,” Dr. Toner said.

A genetic revolution?

While many important IVF innovations were achieved in countries with staunch government support, one of the remarkable things about IVF’s evolution in the United States is that so many occurred with virtually none.

By the mid-1990s, most of the early practitioners had moved from academic settings into private practice, though they continued to publish. “After a while it didn’t help to be in academics. It just sort of slowed you down. Because you weren’t going to get any [government] money anyway, you might as well be in a place that’s a little more nimble,” Dr. Toner said.

At the same time, he said, IVF remains a costly, usually unreimbursed procedure – limiting patients’ willingness to take part in randomized trials. “IVF research is built more on cohort studies.”

Most of the current research focus in IVF is on possibilities for genetic screening. Dr. Miller said that rapid DNA sequencing is allowing specialists to “look at more, pick up more abnormalities. That will continue to improve so that we will be able to see virtually everything.”

But he cautioned there is still much to be done in IVF apart from the genetics – he’s concerned, he said, that the field has moved too far from its surgical origins, and is working with the academic societies to encourage more surgical training.

“We don’t do the same work we did before on fallopian tubes, which is good,” Dr. Miller said, noting that there have been many advances, particularly minimally invasive surgeries in the uterus or ovaries, that have occurred parallel to IVF and can improve success rates. “I think we have a better understanding of what kind of patients require surgical treatments and what kind of surgeries can help enhance fertility, and also what not to do.”

Dr. Bustillo said that “cytogenetics is wonderful, but not everything. You have embryos that are genetically normal and still don’t implant. There’s a lot of work to be done on the interaction between the mother and the embryo.”

Dr. Marrs said that even safety questions related to stimulation have yet to be fully answered. “I’ve always been a big believer that lower is better, but we need to know whether stimulation creates genetic abnormalities and whether less stimulation produces fewer – and we need more data to prove it,” he said. Dr. Marrs is an investigator on a national randomized trial comparing outcomes from IVF with standard-dose and ultra-low dose stimulation.

Access, income, and age

The IVF pioneers agree broadly that access to IVF is nowhere near what it should be in the United States, where only 15 states mandate any insurance coverage for infertility.

“Our limited access to care is a crime,” Dr. Toner said. “People who, through no fault of their own, find themselves infertile are asked to write a check for $15,000 to get pregnant. That’s not fair.”

Dr. DeCherney called access “an ethical issue, because who gets IVF? People with higher incomes. And if IVF allows you to select better embryos – whatever that means – it gives that group another advantage.”

Dr. Toner warned that the push toward genetic testing of embryos, especially in the absence of known hereditary disease, could create new problems for the profession – not unlike in the early days of IVF, when the Jones Institute and other clinics were picketed over the specter of “test tube babies.”

“It’s one thing to say this embryo does not have the right number of chromosomes and couldn’t possibly be a child, so let’s not use it, but what about looking for traits? Sex selection? We have this privileged position in which the government does not really interfere in what we do, but to retain this status we need to stay within the bounds that our society accepts,” Dr. Toner said.

In recent years, IVF uptake has been high among women of advanced reproductive age, which poses its own set of challenges. Outcomes in older women using their own eggs become progressively poorer with age, though donor eggs drastically improve their chances, and egg freezing offers the possibility of preserving quality eggs for later pregnancies.

“We could make this situation better by promoting social freezing, doing more work for women early in their lives to get out their own eggs and store them,” Dr. Miller said. “But again, you still face the issue of access.”

Regardless of what technologies are available or become available in assisted reproduction, doctors and women alike need to be better educated on their options and chances early, with a clearer understanding of what happens as they age, Dr. Bustillo said.

“This is not to pressure them, but just so they understand that when they get to be 42 and are just thinking about reproducing, it’s not a major surprise when I tell them this could be a problem,” she said.

Throughout 2016, Ob.Gyn. News is celebrating its 50th anniversary with exclusive articles looking at the evolution of the specialty, including the history of contraception, changes in gynecologic surgery, and the transformation of the well-woman visit.

The dilemma of a diminishing workforce pool might seem more the province of medical school deans, psychiatry department chairs, and psychiatry residency training directors, but our ability to recruit and retain psychiatrists is, in reality, everyone’s concern—including hospitals, clinics, and, especially, patients and their families. Even without knowledge of the specialty or any numerical appraisal, for example, it is common knowledge that we have a dire shortage of child and adolescent and geriatric psychiatrists—a topic of widespread interest and great consequence for access to mental health care.

Tracking a decline

The very title of a recent provocative paper¹ in Health Affairs says it all: “Population of US practicing psychiatrists declined 2003-13, which may help explain poor access to mental health care.” In an elegant analysis, the authors expose (1) a 10% decline in the number of psychiatrists for every 100,000 people and (2) wide regional variability in the availability of psychiatrists. In stark contrast, the number of neurologists increased by >15% and the primary care workforce remained stable, with a 1.3% increase in the number of physicians, over the same 10 years.

At the beginning of the psychiatry workforce pipeline, the number of medical students who choose psychiatry remains both small (typically, slightly more than 4% of graduating students) and remarkably stable over time. Wilbanks et al,² in a thoughtful analysis of the 2011 to 2013 Medical School Graduation Questionnaire of the Association of American Medical Colleges, affirm and, in part, explain this consistent pattern. They note that the 4 most important considerations among students who select psychiatry are:

• personality fit
• specialty content
• work–life balance
• role model influences.

Some of these considerations also overlap with those of students in other specialties; the authors also note that older medical students and women are more likely to choose psychiatry.

Here is what we must do to erase the shortage

It does appear that, despite scientific advances in brain and behavior, expanding therapeutic options, and unique patient interactions that, taken together, should make a career in psychiatry exciting and appealing, there are simply not enough of us to meet the population’s mental health needs. This is a serious problem. It is our professional obligation—all of us—that we take on this shortage and develop solutions to it.

At its zenith, only about 7% of medical students chose psychiatry. We need to proactively prime the pump for our specialty by encouraging more observerships and promoting mental health careers through community outreach to high school students.

We must be diligent and effective mentors to medical students; mentorship is a powerful catalyst for career decision-making.

We need to make psychiatry clerkships exciting, to show off the best of what our specialty has to offer, and to cultivate sustained interest among our students in the brain and its psychiatric disorders.

We need to highlight the momentous advances in knowledge, biology, and treatments that now characterize our psychiatric profession. We need to advocate for more of these accomplishments.

We must be public stigma-busters! (Our patients need us to do this, too.)

And there is more to do:

Collaborate. In delivering psychiatric health care, we need to expand our effectiveness to achieve more collaboration, greater extension of effect, and broader outreach. Collaborative care has come of age as a delivery model; it should be embraced more broadly. We need to continue our efforts to bridge the many sister mental health disciplines—psychology, nursing, social work, counseling—that collectively provide mental health care.

Unite. Given the inadequate workforce numbers and enormous need, we will diminish ourselves by “guild infighting” and, consequently, weaken our legislative advocacy and leverage. We need to embrace and support all medical specialties and have them support us as well. We need to grow closer to primary care and support this specialty as the true front line of mental health. We also need to bridge the gap between addiction medicine and psychiatry, especially given the high level of addiction comorbidity in many psychiatric disorders.

Foster innovation. The deficit of psychiatric workers might be buffered by innovations in how we leverage our expertise. Telepsychiatry, for example, is clearly advancing, and brings psychiatry to remote areas where psychiatrists are scarce. Mobile health also has great potential for mental health. As one of us (H.A.N.) highlighted recently,³ as genetics become more molecular, what has been the potential of clinically applicable pharmacogenomics might become reality. Psychiatry needs to make progress toward personalized medicine because the disorders we treat are extremely heterogeneous in their etiology, phenomenology, treatment response, and outcomes.

The appeal of working with mind and brain

The extent to which we can convey unfettered optimism about the role of psychiatry in medicine and the relentless progress in neurobiological research, together, will go a long way toward attracting the best and brightest newly minted physicians to our specialty. The brain is the last frontier in medicine; psychiatry is intimately tethered to its unfolding complexity. With millennials placing a higher premium on work–life issues, the enviable balance and quality of life of a psychiatric career might now be particularly opportune, enhancing the quantity and quality of professionals that we can attract to psychiatry.
 

The dilemma of a diminishing workforce pool might seem more the province of medical school deans, psychiatry department chairs, and psychiatry residency training directors, but our ability to recruit and retain psychiatrists is, in reality, everyone’s concern—including hospitals, clinics, and, especially, patients and their families. Even without knowledge of the specialty or any numerical appraisal, for example, it is common knowledge that we have a dire shortage of child and adolescent and geriatric psychiatrists—a topic of widespread interest and great consequence for access to mental health care.

Tracking a decline

The very title of a recent provocative paper¹ in Health Affairs says it all: “Population of US practicing psychiatrists declined 2003-13, which may help explain poor access to mental health care.” In an elegant analysis, the authors expose (1) a 10% decline in the number of psychiatrists for every 100,000 people and (2) wide regional variability in the availability of psychiatrists. In stark contrast, the number of neurologists increased by >15% and the primary care workforce remained stable, with a 1.3% increase in the number of physicians, over the same 10 years.

At the beginning of the psychiatry workforce pipeline, the number of medical students who choose psychiatry remains both small (typically, slightly more than 4% of graduating students) and remarkably stable over time. Wilbanks et al,² in a thoughtful analysis of the 2011 to 2013 Medical School Graduation Questionnaire of the Association of American Medical Colleges, affirm and, in part, explain this consistent pattern. They note that the 4 most important considerations among students who select psychiatry are:

• personality fit
• specialty content
• work–life balance
• role model influences.

Some of these considerations also overlap with those of students in other specialties; the authors also note that older medical students and women are more likely to choose psychiatry.

Here is what we must do to erase the shortage

It does appear that, despite scientific advances in brain and behavior, expanding therapeutic options, and unique patient interactions that, taken together, should make a career in psychiatry exciting and appealing, there are simply not enough of us to meet the population’s mental health needs. This is a serious problem. It is our professional obligation—all of us—that we take on this shortage and develop solutions to it.

At its zenith, only about 7% of medical students chose psychiatry. We need to proactively prime the pump for our specialty by encouraging more observerships and promoting mental health careers through community outreach to high school students.

We must be diligent and effective mentors to medical students; mentorship is a powerful catalyst for career decision-making.

We need to make psychiatry clerkships exciting, to show off the best of what our specialty has to offer, and to cultivate sustained interest among our students in the brain and its psychiatric disorders.

We need to highlight the momentous advances in knowledge, biology, and treatments that now characterize our psychiatric profession. We need to advocate for more of these accomplishments.

We must be public stigma-busters! (Our patients need us to do this, too.)

And there is more to do:

Collaborate. In delivering psychiatric health care, we need to expand our effectiveness to achieve more collaboration, greater extension of effect, and broader outreach. Collaborative care has come of age as a delivery model; it should be embraced more broadly. We need to continue our efforts to bridge the many sister mental health disciplines—psychology, nursing, social work, counseling—that collectively provide mental health care.

Unite. Given the inadequate workforce numbers and enormous need, we will diminish ourselves by “guild infighting” and, consequently, weaken our legislative advocacy and leverage. We need to embrace and support all medical specialties and have them support us as well. We need to grow closer to primary care and support this specialty as the true front line of mental health. We also need to bridge the gap between addiction medicine and psychiatry, especially given the high level of addiction comorbidity in many psychiatric disorders.

Foster innovation. The deficit of psychiatric workers might be buffered by innovations in how we leverage our expertise. Telepsychiatry, for example, is clearly advancing, and brings psychiatry to remote areas where psychiatrists are scarce. Mobile health also has great potential for mental health. As one of us (H.A.N.) highlighted recently,³ as genetics become more molecular, what has been the potential of clinically applicable pharmacogenomics might become reality. Psychiatry needs to make progress toward personalized medicine because the disorders we treat are extremely heterogeneous in their etiology, phenomenology, treatment response, and outcomes.

The appeal of working with mind and brain

The extent to which we can convey unfettered optimism about the role of psychiatry in medicine and the relentless progress in neurobiological research, together, will go a long way toward attracting the best and brightest newly minted physicians to our specialty. The brain is the last frontier in medicine; psychiatry is intimately tethered to its unfolding complexity. With millennials placing a higher premium on work–life issues, the enviable balance and quality of life of a psychiatric career might now be particularly opportune, enhancing the quantity and quality of professionals that we can attract to psychiatry.
 

The dilemma of a diminishing workforce pool might seem more the province of medical school deans, psychiatry department chairs, and psychiatry residency training directors, but our ability to recruit and retain psychiatrists is, in reality, everyone’s concern—including hospitals, clinics, and, especially, patients and their families. Even without knowledge of the specialty or any numerical appraisal, for example, it is common knowledge that we have a dire shortage of child and adolescent and geriatric psychiatrists—a topic of widespread interest and great consequence for access to mental health care.

Tracking a decline

The very title of a recent provocative paper¹ in Health Affairs says it all: “Population of US practicing psychiatrists declined 2003-13, which may help explain poor access to mental health care.” In an elegant analysis, the authors expose (1) a 10% decline in the number of psychiatrists for every 100,000 people and (2) wide regional variability in the availability of psychiatrists. In stark contrast, the number of neurologists increased by >15% and the primary care workforce remained stable, with a 1.3% increase in the number of physicians, over the same 10 years.

At the beginning of the psychiatry workforce pipeline, the number of medical students who choose psychiatry remains both small (typically, slightly more than 4% of graduating students) and remarkably stable over time. Wilbanks et al,² in a thoughtful analysis of the 2011 to 2013 Medical School Graduation Questionnaire of the Association of American Medical Colleges, affirm and, in part, explain this consistent pattern. They note that the 4 most important considerations among students who select psychiatry are:

• personality fit
• specialty content
• work–life balance
• role model influences.

Some of these considerations also overlap with those of students in other specialties; the authors also note that older medical students and women are more likely to choose psychiatry.

Here is what we must do to erase the shortage

It does appear that, despite scientific advances in brain and behavior, expanding therapeutic options, and unique patient interactions that, taken together, should make a career in psychiatry exciting and appealing, there are simply not enough of us to meet the population’s mental health needs. This is a serious problem. It is our professional obligation—all of us—that we take on this shortage and develop solutions to it.

At its zenith, only about 7% of medical students chose psychiatry. We need to proactively prime the pump for our specialty by encouraging more observerships and promoting mental health careers through community outreach to high school students.

We must be diligent and effective mentors to medical students; mentorship is a powerful catalyst for career decision-making.

We need to make psychiatry clerkships exciting, to show off the best of what our specialty has to offer, and to cultivate sustained interest among our students in the brain and its psychiatric disorders.

We need to highlight the momentous advances in knowledge, biology, and treatments that now characterize our psychiatric profession. We need to advocate for more of these accomplishments.

We must be public stigma-busters! (Our patients need us to do this, too.)

And there is more to do:

Collaborate. In delivering psychiatric health care, we need to expand our effectiveness to achieve more collaboration, greater extension of effect, and broader outreach. Collaborative care has come of age as a delivery model; it should be embraced more broadly. We need to continue our efforts to bridge the many sister mental health disciplines—psychology, nursing, social work, counseling—that collectively provide mental health care.

Unite. Given the inadequate workforce numbers and enormous need, we will diminish ourselves by “guild infighting” and, consequently, weaken our legislative advocacy and leverage. We need to embrace and support all medical specialties and have them support us as well. We need to grow closer to primary care and support this specialty as the true front line of mental health. We also need to bridge the gap between addiction medicine and psychiatry, especially given the high level of addiction comorbidity in many psychiatric disorders.

Foster innovation. The deficit of psychiatric workers might be buffered by innovations in how we leverage our expertise. Telepsychiatry, for example, is clearly advancing, and brings psychiatry to remote areas where psychiatrists are scarce. Mobile health also has great potential for mental health. As one of us (H.A.N.) highlighted recently,³ as genetics become more molecular, what has been the potential of clinically applicable pharmacogenomics might become reality. Psychiatry needs to make progress toward personalized medicine because the disorders we treat are extremely heterogeneous in their etiology, phenomenology, treatment response, and outcomes.

The appeal of working with mind and brain

The extent to which we can convey unfettered optimism about the role of psychiatry in medicine and the relentless progress in neurobiological research, together, will go a long way toward attracting the best and brightest newly minted physicians to our specialty. The brain is the last frontier in medicine; psychiatry is intimately tethered to its unfolding complexity. With millennials placing a higher premium on work–life issues, the enviable balance and quality of life of a psychiatric career might now be particularly opportune, enhancing the quantity and quality of professionals that we can attract to psychiatry.
 

The platysma muscle has been widely studied in its course through the cervical region in an attempt to develop more effective surgical approaches for rejuvenation. As a person ages, the platysma muscle becomes thinner, less defined, and ptotic, which results in the clinical appearance of a sagging neck that prompts patients to undergo neck-lift procedures. However, little is known about the course of the platysma in the mid and lower face and the implications on facial aging.

Bae et al (Plast Reconstr Surg. 2016;138:365-371) performed a cadaveric dissection of the facial portion of the platysma muscle to delineate the morphology and extension of the muscle in the mid and lower face. Thirty-four adult hemifaces were dissected. The demographics were broken down by age (mean, 71.4 years; range, 41–93 years), gender (29 men; 5 women), and ethnicity (14 Korean; 20 Thai). The extension of the platysma was documented according to a grid the authors created. The grid was divided along 3 horizontal lines (H1–H3) and 3 vertical lines (V1–V3). The intersection of these lines created a grid that was comprised of 3×3 squares and was labeled superior (S1–S3), middle (M1–M3), and inferior (I1–I3). H1 was a line drawn horizontally from the tragus to the lateral orbit, H2 was a line from the earlobe to the nasal ala, and H3 was a line from the angle of the mandible to the corner of the mouth.

The extension pattern of the facial portion of the platysma muscle was classified into patterns: A (n=3; S1–S2, M1–M3, and I1-I3 were covered by the muscle), B-1 (n=20; M1–M3, I1–I3), B-2 (n=9; M1–M2, I1–I3), and C (n=2; I1-I3).

The platysma muscle is divided into anterior and posterior portions. The anterior platysma ascends superiorly and medially in the face to interdigitate with the depressor anguli oris and the depressor labii inferioris muscles. The morphology pattern of the posterior platysma varied and was classified into 1 of 3 patterns: straight (n=13), straight-curved (n=18), and curved (n=3). The straight pattern showed platysma fibers that travel parallel to the mandibular malar line and head toward the zygomaticus major or the orbicularis oculi muscles. The straight-curved type has fibers that travel straight from the neck to the face but then curve, heading toward the risorius, zygomaticus major, or orbicularis oculi muscle depending on the extent of the platysma muscle in the area. The curved type has fibers that run parallel to the zygomaticus arch and interdigitate with the orbicularis oculi muscle and either the risorius or zygomaticus major muscle.

What’s the issue?

For many years, the cervical platysma muscle was studied and surgical approaches were modified to enhance results. The authors of this study have taken the study of the platysma muscle further to delineate its course through the face. Knowledge of the various pathways of the muscle can help us determine the most natural direction to resuspend ptotic facial tissue during surgery and minimally invasive procedures such as thread-lifting. The most salient points include: (1) the lower one-third of the masseter muscle is covered by the platysma, and (2) straight-curved was the most common morphology type, suggesting that the vector for repositioning the platysma muscle is vertical.

Although Bae et al do not discuss the use of botulinum toxin (BTX) in the treatment of the platysma, the results of this study further support the importance of BTX to the lower face. We can look back at more than 14 years of cosmetic use of BTX for the glabella and see the reduced number of brow-lift surgeries nationwide. Although the preventative effects of BTX on brow depression still need to be scientifically proven, it may behoove us to think preventatively on the use of BTX in the platysma to minimize ptosis of the lower face and neck. The results of this anatomic study support the importance of tailoring the approach to the dynamic lines caused by the platysma muscle in each patient to address jowls and neck bands. Have you been offering lower face BTX treatments to patients in an effort to reduce lower face aging?

We want to know your views! Tell us what you think.

The platysma muscle has been widely studied in its course through the cervical region in an attempt to develop more effective surgical approaches for rejuvenation. As a person ages, the platysma muscle becomes thinner, less defined, and ptotic, which results in the clinical appearance of a sagging neck that prompts patients to undergo neck-lift procedures. However, little is known about the course of the platysma in the mid and lower face and the implications on facial aging.

Bae et al (Plast Reconstr Surg. 2016;138:365-371) performed a cadaveric dissection of the facial portion of the platysma muscle to delineate the morphology and extension of the muscle in the mid and lower face. Thirty-four adult hemifaces were dissected. The demographics were broken down by age (mean, 71.4 years; range, 41–93 years), gender (29 men; 5 women), and ethnicity (14 Korean; 20 Thai). The extension of the platysma was documented according to a grid the authors created. The grid was divided along 3 horizontal lines (H1–H3) and 3 vertical lines (V1–V3). The intersection of these lines created a grid that was comprised of 3×3 squares and was labeled superior (S1–S3), middle (M1–M3), and inferior (I1–I3). H1 was a line drawn horizontally from the tragus to the lateral orbit, H2 was a line from the earlobe to the nasal ala, and H3 was a line from the angle of the mandible to the corner of the mouth.

The extension pattern of the facial portion of the platysma muscle was classified into patterns: A (n=3; S1–S2, M1–M3, and I1-I3 were covered by the muscle), B-1 (n=20; M1–M3, I1–I3), B-2 (n=9; M1–M2, I1–I3), and C (n=2; I1-I3).

The platysma muscle is divided into anterior and posterior portions. The anterior platysma ascends superiorly and medially in the face to interdigitate with the depressor anguli oris and the depressor labii inferioris muscles. The morphology pattern of the posterior platysma varied and was classified into 1 of 3 patterns: straight (n=13), straight-curved (n=18), and curved (n=3). The straight pattern showed platysma fibers that travel parallel to the mandibular malar line and head toward the zygomaticus major or the orbicularis oculi muscles. The straight-curved type has fibers that travel straight from the neck to the face but then curve, heading toward the risorius, zygomaticus major, or orbicularis oculi muscle depending on the extent of the platysma muscle in the area. The curved type has fibers that run parallel to the zygomaticus arch and interdigitate with the orbicularis oculi muscle and either the risorius or zygomaticus major muscle.

What’s the issue?

For many years, the cervical platysma muscle was studied and surgical approaches were modified to enhance results. The authors of this study have taken the study of the platysma muscle further to delineate its course through the face. Knowledge of the various pathways of the muscle can help us determine the most natural direction to resuspend ptotic facial tissue during surgery and minimally invasive procedures such as thread-lifting. The most salient points include: (1) the lower one-third of the masseter muscle is covered by the platysma, and (2) straight-curved was the most common morphology type, suggesting that the vector for repositioning the platysma muscle is vertical.

Although Bae et al do not discuss the use of botulinum toxin (BTX) in the treatment of the platysma, the results of this study further support the importance of BTX to the lower face. We can look back at more than 14 years of cosmetic use of BTX for the glabella and see the reduced number of brow-lift surgeries nationwide. Although the preventative effects of BTX on brow depression still need to be scientifically proven, it may behoove us to think preventatively on the use of BTX in the platysma to minimize ptosis of the lower face and neck. The results of this anatomic study support the importance of tailoring the approach to the dynamic lines caused by the platysma muscle in each patient to address jowls and neck bands. Have you been offering lower face BTX treatments to patients in an effort to reduce lower face aging?

We want to know your views! Tell us what you think.

The platysma muscle has been widely studied in its course through the cervical region in an attempt to develop more effective surgical approaches for rejuvenation. As a person ages, the platysma muscle becomes thinner, less defined, and ptotic, which results in the clinical appearance of a sagging neck that prompts patients to undergo neck-lift procedures. However, little is known about the course of the platysma in the mid and lower face and the implications on facial aging.

Bae et al (Plast Reconstr Surg. 2016;138:365-371) performed a cadaveric dissection of the facial portion of the platysma muscle to delineate the morphology and extension of the muscle in the mid and lower face. Thirty-four adult hemifaces were dissected. The demographics were broken down by age (mean, 71.4 years; range, 41–93 years), gender (29 men; 5 women), and ethnicity (14 Korean; 20 Thai). The extension of the platysma was documented according to a grid the authors created. The grid was divided along 3 horizontal lines (H1–H3) and 3 vertical lines (V1–V3). The intersection of these lines created a grid that was comprised of 3×3 squares and was labeled superior (S1–S3), middle (M1–M3), and inferior (I1–I3). H1 was a line drawn horizontally from the tragus to the lateral orbit, H2 was a line from the earlobe to the nasal ala, and H3 was a line from the angle of the mandible to the corner of the mouth.

The extension pattern of the facial portion of the platysma muscle was classified into patterns: A (n=3; S1–S2, M1–M3, and I1-I3 were covered by the muscle), B-1 (n=20; M1–M3, I1–I3), B-2 (n=9; M1–M2, I1–I3), and C (n=2; I1-I3).

The platysma muscle is divided into anterior and posterior portions. The anterior platysma ascends superiorly and medially in the face to interdigitate with the depressor anguli oris and the depressor labii inferioris muscles. The morphology pattern of the posterior platysma varied and was classified into 1 of 3 patterns: straight (n=13), straight-curved (n=18), and curved (n=3). The straight pattern showed platysma fibers that travel parallel to the mandibular malar line and head toward the zygomaticus major or the orbicularis oculi muscles. The straight-curved type has fibers that travel straight from the neck to the face but then curve, heading toward the risorius, zygomaticus major, or orbicularis oculi muscle depending on the extent of the platysma muscle in the area. The curved type has fibers that run parallel to the zygomaticus arch and interdigitate with the orbicularis oculi muscle and either the risorius or zygomaticus major muscle.

What’s the issue?

For many years, the cervical platysma muscle was studied and surgical approaches were modified to enhance results. The authors of this study have taken the study of the platysma muscle further to delineate its course through the face. Knowledge of the various pathways of the muscle can help us determine the most natural direction to resuspend ptotic facial tissue during surgery and minimally invasive procedures such as thread-lifting. The most salient points include: (1) the lower one-third of the masseter muscle is covered by the platysma, and (2) straight-curved was the most common morphology type, suggesting that the vector for repositioning the platysma muscle is vertical.

Although Bae et al do not discuss the use of botulinum toxin (BTX) in the treatment of the platysma, the results of this study further support the importance of BTX to the lower face. We can look back at more than 14 years of cosmetic use of BTX for the glabella and see the reduced number of brow-lift surgeries nationwide. Although the preventative effects of BTX on brow depression still need to be scientifically proven, it may behoove us to think preventatively on the use of BTX in the platysma to minimize ptosis of the lower face and neck. The results of this anatomic study support the importance of tailoring the approach to the dynamic lines caused by the platysma muscle in each patient to address jowls and neck bands. Have you been offering lower face BTX treatments to patients in an effort to reduce lower face aging?

We want to know your views! Tell us what you think.

For the last decade, we have considered the cardioprotective benefit of biologics, especially in patients with chronic inflammatory diseases. Due to accelerated coronary artery disease, inflammatory pathways of psoriasis share connections with the mechanisms of atherosclerosis.

In a July 7 article published online in JAMA Dermatology, Hjuler et al investigated the association of biological therapy with changes in coronary artery disease progression, measured by serial coronary computed tomography (CT). Patients with severe psoriasis were enrolled in a single-center, prospective, controlled, observer-blinded clinical study. Between April 2011 and June 2014, biologic therapy (intervention group) and a matched control that did not receive the same therapy (control group) were initiated. Biological therapies included adalimumab, etanercept, infliximab, and ustekinumab, along with the possibility to switch between treatments to ensure inflammation control.

At baseline and 13-month follow-up, 28 treated patients (mean age [SD], 49.2 [10.2] years; 71% men; mean psoriasis area severity index [PASI][SD], 15.4 [4.3]) and 28 controls (mean age [SD], 52.8 [10.6] years; 71% men; mean PASI [SD], 12.4 [3.9]) underwent noncontrast coronary artery calcium (CAC) CT and contrast-enhanced coronary CT angiography. Changes in CAC score, number of coronary plaques, severity of luminal narrowing, composition, and vessel wall volume were measured.

In the intervention group, the CAC scores remained stable (mean yearly CAC change [SD], -16 [56]; P=.15) and progressed in the control group (14 [29]; P=.02). The severity of luminal narrowing in the diseased segments remained unchanged in the intervention group (Wilcoxon W=76; n=483; P=.39) but increased at follow-up in the control group (Wilcoxon W=281; n=414; P=.02). Luminal abnormalities remained unchanged in both groups.

The authors concluded that clinically effective treatment with biologic agents is associated with reduced coronary artery diseases in patients with severe psoriasis. These findings support a beneficial effect of biologic anti-inflammatory agents in preventing cardiovascular disease progression in addition to disease control in inflammatory diseases.

What’s the issue?

These findings give continued support to the cardioprotective effects of biologics in inflammatory diseases. How will these data change your prescribing habits?

We want to know your views! Tell us what you think.

For the last decade, we have considered the cardioprotective benefit of biologics, especially in patients with chronic inflammatory diseases. Due to accelerated coronary artery disease, inflammatory pathways of psoriasis share connections with the mechanisms of atherosclerosis.

In a July 7 article published online in JAMA Dermatology, Hjuler et al investigated the association of biological therapy with changes in coronary artery disease progression, measured by serial coronary computed tomography (CT). Patients with severe psoriasis were enrolled in a single-center, prospective, controlled, observer-blinded clinical study. Between April 2011 and June 2014, biologic therapy (intervention group) and a matched control that did not receive the same therapy (control group) were initiated. Biological therapies included adalimumab, etanercept, infliximab, and ustekinumab, along with the possibility to switch between treatments to ensure inflammation control.

At baseline and 13-month follow-up, 28 treated patients (mean age [SD], 49.2 [10.2] years; 71% men; mean psoriasis area severity index [PASI][SD], 15.4 [4.3]) and 28 controls (mean age [SD], 52.8 [10.6] years; 71% men; mean PASI [SD], 12.4 [3.9]) underwent noncontrast coronary artery calcium (CAC) CT and contrast-enhanced coronary CT angiography. Changes in CAC score, number of coronary plaques, severity of luminal narrowing, composition, and vessel wall volume were measured.

In the intervention group, the CAC scores remained stable (mean yearly CAC change [SD], -16 [56]; P=.15) and progressed in the control group (14 [29]; P=.02). The severity of luminal narrowing in the diseased segments remained unchanged in the intervention group (Wilcoxon W=76; n=483; P=.39) but increased at follow-up in the control group (Wilcoxon W=281; n=414; P=.02). Luminal abnormalities remained unchanged in both groups.

The authors concluded that clinically effective treatment with biologic agents is associated with reduced coronary artery diseases in patients with severe psoriasis. These findings support a beneficial effect of biologic anti-inflammatory agents in preventing cardiovascular disease progression in addition to disease control in inflammatory diseases.

What’s the issue?

These findings give continued support to the cardioprotective effects of biologics in inflammatory diseases. How will these data change your prescribing habits?

We want to know your views! Tell us what you think.

For the last decade, we have considered the cardioprotective benefit of biologics, especially in patients with chronic inflammatory diseases. Due to accelerated coronary artery disease, inflammatory pathways of psoriasis share connections with the mechanisms of atherosclerosis.

In a July 7 article published online in JAMA Dermatology, Hjuler et al investigated the association of biological therapy with changes in coronary artery disease progression, measured by serial coronary computed tomography (CT). Patients with severe psoriasis were enrolled in a single-center, prospective, controlled, observer-blinded clinical study. Between April 2011 and June 2014, biologic therapy (intervention group) and a matched control that did not receive the same therapy (control group) were initiated. Biological therapies included adalimumab, etanercept, infliximab, and ustekinumab, along with the possibility to switch between treatments to ensure inflammation control.

At baseline and 13-month follow-up, 28 treated patients (mean age [SD], 49.2 [10.2] years; 71% men; mean psoriasis area severity index [PASI][SD], 15.4 [4.3]) and 28 controls (mean age [SD], 52.8 [10.6] years; 71% men; mean PASI [SD], 12.4 [3.9]) underwent noncontrast coronary artery calcium (CAC) CT and contrast-enhanced coronary CT angiography. Changes in CAC score, number of coronary plaques, severity of luminal narrowing, composition, and vessel wall volume were measured.

In the intervention group, the CAC scores remained stable (mean yearly CAC change [SD], -16 [56]; P=.15) and progressed in the control group (14 [29]; P=.02). The severity of luminal narrowing in the diseased segments remained unchanged in the intervention group (Wilcoxon W=76; n=483; P=.39) but increased at follow-up in the control group (Wilcoxon W=281; n=414; P=.02). Luminal abnormalities remained unchanged in both groups.

The authors concluded that clinically effective treatment with biologic agents is associated with reduced coronary artery diseases in patients with severe psoriasis. These findings support a beneficial effect of biologic anti-inflammatory agents in preventing cardiovascular disease progression in addition to disease control in inflammatory diseases.

What’s the issue?

These findings give continued support to the cardioprotective effects of biologics in inflammatory diseases. How will these data change your prescribing habits?

We want to know your views! Tell us what you think.

In 1961 before Congress, and in 1962 at Rice University, Houston, President John F. Kennedy called on America to land a man on the moon and bring him back safely, and to look beyond the moon as well, and pursue an ambitious space exploration program. He challenged the country to think and act boldly, telling Americans in his speech at Rice that “we choose to go the moon in this decade and do the other things, not because they are easy, but because they are hard.”

When Neil Armstrong and Buzz Aldrin set foot on the moon in 1969 – even before President Kennedy’s 10-year deadline had arrived – the country’s primary moonshot was realized. The President had inspired the nation, teams of engineers and others had collectively met daunting technological challenges, and space consequently was more open to us than ever before.

In looking at the field of obstetrics and how far it has come in the past 50 years, since the 1960s, it is similarly astonishing and inspiring to reflect on what extraordinary advances we have made. Who would have thought that the fetus would become such a visible and intimate patient – one who, like the mother, can be interrogated, monitored, and sometimes treated before birth? Who would have thought we would be utilizing genomic studies in a now well-established field of prenatal diagnosis, or that fetal therapy would become a field in and of itself?

Our specialty has advanced through a series of moonshots that have been inspired and driven by technological advancement and by our continually bold goals and vision for the health and well-being of women and their offspring. We have taken on ambitious challenges, achieved many goals, and embraced advancements in practice only to then set new targets that previously were unimaginable.

Yet just as our country’s space exploration program has faced disappointments, so has our field. It is sobering, for instance, that we have made only incremental improvements in prematurity and infant mortality, and that the age-old maternal problem of preeclampsia is still with us. We also face new challenges, such as the rising rate of maternal obesity and diabetes, which threaten both maternal and fetal health.

President Kennedy spoke of having “examined where we are strong, and where we are not.” Such self-reflection and assessment is a critical underpinning of advancement in fields across all of science, medicine, and health care, and in our specialty, it is a process that has driven ambitious new research efforts to improve fetal and maternal health.

A step back to more in-depth fundamental research on the biomolecular mechanisms of premature labor and diabetes-associated birth defects, for instance, as well as new efforts to approach fetal surgery less invasively, are positioning us to both conquer our disappointments and achieve ambitious new moonshots.

The fetus as our patient

Fifty years ago, in 1966, a seminal paper in the Lancet reported that amniotic fluid cells could be cultured and were suitable for karyotyping (1[7434]:383-5). The tapping and examination of amniotic fluid had been reported on sporadically for many decades, for various clinical purposes, but by and large the fetal compartment was not invaded or directly examined. The fetus was instead the hopeful beneficiary of pregnancy care that focused on the mother. Fetal outcome was clouded in mystery, known only at birth.

With the Lancet report, prenatal detection of chromosomal disorders began to feel achievable, and the 1960s marked the beginning of a journey first through invasive methods of prenatal diagnosis and then through increasingly non-invasive approaches.

In 1970, just several years after the report on chromosome analysis of amniotic-fluid cells, another landmark paper in the New England Journal of Medicine described 162 amniocenteses performed between the 13th and 18th weeks of gestation and the detection of 10 cases of Down syndrome, as well as a few other cases of metabolic and other disorders (282[11]:596-9). This report provided an impetus for broader use of the procedure to detect neural tube defects, Down syndrome, and other abnormalities.

The adoption of amniocentesis for prenatal diagnosis still took some time, however. The procedure was used primarily early on to determine fetal lung maturity, and to predict the ability of the fetus to survive after delivery.

At the time, it was widely praised as an advanced method for evaluating the fetus. Yet, looking back, the early years of the procedure seem primitive. The procedure was done late in pregnancy and it was performed blindly, with the puncture site located either with external palpation of the uterus or with the assistance of static ultrasound. Patients who had scans would usually visit the radiologist, who would mark on the patient’s abdomen a suggested location for needle insertion. Upon the patient’s return, the obstetrician would then insert a needle into that spot, blindly and likely after the fetus had moved.

The development and adoption of real-time ultrasound was a revolutionary achievement. Ultrasound-guided amniocentesis was first described in 1972, 14 years after Ian Donald’s seminal paper introducing obstetric ultrasound was published in the Lancet (1958 Jun 7;1[7032]:1188-95).

As real-time ultrasound made its way into practice, it marked the true realization of a moonshot for obstetrics.

Not only could we simultaneously visualize the needle tip and place the needle safety, but we could see the real-time movement of the fetus, its activity, and the surrounding pockets of fluid. It was like looking up into the sky and seeing the stars for the first time. We could see fetal arrhythmia – not only hear it. With this window into the fetal compartment, we could visualize the fetal bowel migrating into the chest cavity due to a hole (hernia) in the diaphragm. We could visualize other malformations as well.

Chorionic villus sampling (CVS) was technically more difficult and took longer to evolve. For years, through the early 1980s, it was performed only at select centers throughout the country. Patients traveled for the procedure and faced relatively significant risks of complications.

By the end of the 1980s, however, with successive improvements in equipment and technique (including development of a transabdominal approach in addition to transvaginal) the procedure was deemed safe, effective, and acceptable for routine use. Fetoscopy, pioneered by John Hobbins, MD, and his colleagues at Yale University, New Haven, Conn., had also advanced and was being used to diagnose sickle cell anemia, Tay-Sachs disease, congenital fetal skin diseases, and other disorders.

With these advances and with our newfound ability to obtain and analyze a tissue sample earlier in pregnancy – even before a woman shared the news of her pregnancy, in some cases – it seemed that we had achieved our goals and may have even reached past the moon.

Yet there were other moonshots being pursued, including initiatives to make prenatal diagnosis less invasive. The discovery in 1997 of cell-free fetal DNA in maternal plasma and serum, for instance, was a pivotal development that opened the door for noninvasive prenatal testing.

This, and other advances in areas from biochemistry to ultrasound to genomic analysis, led to an array of prenatal diagnostic tools that today enable women and their physicians to assess the genetic, chromosomal, and biophysical aspects of their fetus considerably before the time of viability, and from both the maternal side and directly in the fetal compartment.

First-trimester screening is a current option, and we now have the ability to more selectively perform amniocentesis and CVS based on probability testing, and not solely on maternal age. Ultrasound technology now encompasses color Doppler, 3D and 4D imaging, and other techniques that can be used to assess the placenta, various structures inside the brain, and the heart, as well as blood flow through the ductus venosus.

Parents have called for and welcomed having the option of assessing the fetus in greater detail, and of having either assurance when anomalies are excluded or the opportunity to plan and make decisions when anomalies are detected.

Fetal surgery has been a natural extension of our unprecedented access to the fetus. Our ability to visualize malformations and their evolution led to animal studies that advanced our interest in arresting, correcting, or reversing fetal anomalies through in-utero interventions. In 1981, surgeons performed the first human open fetal surgery to correct congenital hydronephrosis.

Today, we can employ endoscopic laser ablation or laser coagulation to treat severe twin-to-twin syndrome, for instance, as well as other surgical techniques to repair defects such as congenital diaphragmatic hernia, lower urinary tract obstruction, and myelomeningocele. Such advances were unimaginable decades ago.

Old foes and new threats

Despite these advances in diagnosis and care, obstetrics faces unrealized moonshots – lingering challenges that, 50 years ago, we would have predicted would have been solved. Who would have thought that we would still have as high an infant mortality rate as we do, and that we would not be further along in solving the problem of prematurity? Our progress has been only incremental.

Fifty years ago, we lacked an understanding of the basic biology of preterm labor. Prematurity was viewed simply as term labor occurring too early, and many efforts were made over the years to halt the premature labor process through the use of various drugs and other therapeutics, with variable and minimally impactful levels of success.

In the last 25 years, and especially in the last decade, we have made greater efforts to better understand the biology of premature labor – to elucidate how and why it occurs – and we have come to understand that premature labor is very different physiologically from term labor.

Thanks to the work at the Perinatology Research Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), led by Roberto Romero, MD, attention has consequently shifted toward prediction, identification of women at highest risk, and prevention of the onset of premature labor among those deemed to be at highest risk.

Cervical length in the mid-trimester is now a well-verified predictor of preterm birth, and vaginal progesterone has been shown to benefit women without other known risk factors who are diagnosed with a shortened cervical length.

We have consequently seen the preterm birth rate decline a bit. In 2013, the last year for which we have complete data, the preterm birth rate dropped to 11.4%, down from a high of 12.8% in 2006, according to the Centers for Disease Control and Prevention.

Infant mortality similarly remains unacceptably high, due largely to the high preterm birth rate and to our failure to significantly alter the prevalence of birth defects. In 2010, according to the CDC, the infant mortality rate in the U.S. was 6.1 deaths per 1,000 live births (compared with 6.87 in 2005), and the United States ranked 26th in infant mortality among countries belonging to the Organisation for Economic Co-operation and Development, despite the fact that we spend a significant portion of our gross domestic product (17.5% in 2014) on health care.

Birth defects have taken over as a leading cause of infant mortality after early newborn life, and while we’ve made some advancements in understanding and diagnosing them, the majority of causes of birth defects are still unknown.

On the maternal side of obstetrical care, our progress has similarly been more modest than we have hoped for. Preeclampsia remains a problem, for instance. Despite decades of research into its pathogenesis, our advancements have been only incremental, and the condition – particularly its severe form – continues to be a vexing and high-risk problem.

Added to such age-old foes, moreover, are the growing threats of maternal obesity and diabetes, two closely related and often chronic conditions that affect not only the health of the mother but the in-utero environment and the health of the fetus. Today, more than one-third of all adults in the U.S., and 34% of women aged 20-39 years, are obese, and almost 10% of the U.S. population has diabetes.

Both conditions are on the rise, and obstetrics is confronting an epidemic of “diabesity” that would not necessarily have been predicted 50 years ago. It is particularly alarming given our growing knowledge of how obesity can be programmed in-utero and essentially passed on from generation to generation, of how diabetes can negatively affect perinatal outcomes, and of how the two conditions can have an additive effect on fetal complications.

Achieving new moonshots

Concerted efforts in the past several decades to step back and try to understand the basic biology and physiology of term labor and of premature labor have better positioned our specialty to achieve the moonshot of significantly reducing the incidence of preterm birth.

Establishment in the mid-1980s of the NICHD’s Perinatology Research Branch was a major development in this regard, helping to build and direct research efforts, including basic laboratory science, toward questions about what triggers and propagates labor. There has been notable progress in the past decade, in particular, and our specialty is now on the right path toward development of therapeutic interventions for preventing prematurity.

Additionally, the NICHD’s recently launched Human Placenta Project is building upon the branch-sponsored animal and cell culture model systems of the placenta to allow researchers, for the first time, to monitor human placental health in real time. By more fully understanding the role of the placenta in health and disease, we will be able to better evaluate pregnancy risks and improve pregnancy outcomes.

We also are learning through research in the University of Maryland Birth Defects Research Laboratory, which I am privileged to direct, and at other facilities, that maternal hyperglycemia is a teratogen, creating insults that can trigger a series of developmental fetal defects. By studying the biomolecular mechanisms of hyperglycemia-induced birth defects and developing “molecular maps,” we expect to be able to develop strategies for preventing or mitigating the development of such anomalies. I hope and expect that these future advancements, combined with reductions in prematurity, will significantly impact the infant mortality rate.

Fetal therapy and surgery will also continue to advance, with a much more minimally invasive approach taken in the next 50 years to addressing the fetal condition without putting the mother at increased risk. Just as surgery in other fields has moved from open laparotomy to minimally invasive techniques, I believe we will develop endoscopic or laparoscopic means of correcting the various problems in-utero, such as the repair of neural tube defects and diaphragmatic hernias. It already appears likely that a fetoscopic approach to treating myelomeningocele can reduce maternal morbidity while achieving infant neurological outcomes that are at least as good as outcomes achieved with open fetal surgery.

We’re in a much different position than we were 50 years ago in that we have two patients – the mother and the fetus – with whom we can closely work. We also have a relatively new and urgent obligation to place our attention not only on women’s reproductive health, but on the general gynecologic state. Ob.gyns. often are the only primary care physicians whom women see for routine care, and the quality of our attention to their weight and their diabetes risk factors will have far-reaching consequences, both for them and for their offspring.

As we have since the 1960s, we will continue to set new moonshots and meet new challenges, working with each other and with our patients to evaluate where we are strong and where we must improve. We will persistently harness the power of technology, choosing to do the things that “are hard,” while stepping back as needed to ask and address fundamental questions.

As a result, I can envision the next 50 years as a revolutionary time period for obstetrics – a time in which current problems and disorders are abated or eliminated through a combination of genomics, microbiomics, and other technological advances. Someday in the future, we will look back on some of our many achievements and marvel at how we have transformed the unimaginable to reality.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].

Select advances through the years

1960s

1965: Siemens Corp. introduces first real-time ultrasound scanner.

1966: Lancet paper reports that amniotic fluid cells can be cultured and karyotyped.

1970s

1970: New England Journal of Medicine paper describes mid-trimester amniocenteses and detection of Down syndrome cases.

1972: Ultrasound-guided amniocentesis first described.

1973: Fetoscopy introduced.

1980s

1981: First human open fetal surgery to correct congenital hydronephrosis.

Early 1980s: Chorionic villus sampling introduced at select centers.

1985: Color Doppler incorporated into ultrasound.

1990s

1990: Embryoscopy first described.

Mid-1990s: 3D/4D ultrasound begins to assume major role in ob.gyn. imaging.1997: Discovery of cell-free fetal DNA in maternal plasma.

2000s

2003: MOMS (Management of Myelomeningocele Study) was launched.

2010s

2012: The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine support cell-free DNA screening for women at increased risk of fetal aneuploidy.

2013: Preterm birth rate drops to 11.4%

2014: Diabetes incidence marks a 4-fold increase since 1980.

In 1961 before Congress, and in 1962 at Rice University, Houston, President John F. Kennedy called on America to land a man on the moon and bring him back safely, and to look beyond the moon as well, and pursue an ambitious space exploration program. He challenged the country to think and act boldly, telling Americans in his speech at Rice that “we choose to go the moon in this decade and do the other things, not because they are easy, but because they are hard.”

When Neil Armstrong and Buzz Aldrin set foot on the moon in 1969 – even before President Kennedy’s 10-year deadline had arrived – the country’s primary moonshot was realized. The President had inspired the nation, teams of engineers and others had collectively met daunting technological challenges, and space consequently was more open to us than ever before.

In looking at the field of obstetrics and how far it has come in the past 50 years, since the 1960s, it is similarly astonishing and inspiring to reflect on what extraordinary advances we have made. Who would have thought that the fetus would become such a visible and intimate patient – one who, like the mother, can be interrogated, monitored, and sometimes treated before birth? Who would have thought we would be utilizing genomic studies in a now well-established field of prenatal diagnosis, or that fetal therapy would become a field in and of itself?

Our specialty has advanced through a series of moonshots that have been inspired and driven by technological advancement and by our continually bold goals and vision for the health and well-being of women and their offspring. We have taken on ambitious challenges, achieved many goals, and embraced advancements in practice only to then set new targets that previously were unimaginable.

Yet just as our country’s space exploration program has faced disappointments, so has our field. It is sobering, for instance, that we have made only incremental improvements in prematurity and infant mortality, and that the age-old maternal problem of preeclampsia is still with us. We also face new challenges, such as the rising rate of maternal obesity and diabetes, which threaten both maternal and fetal health.

President Kennedy spoke of having “examined where we are strong, and where we are not.” Such self-reflection and assessment is a critical underpinning of advancement in fields across all of science, medicine, and health care, and in our specialty, it is a process that has driven ambitious new research efforts to improve fetal and maternal health.

A step back to more in-depth fundamental research on the biomolecular mechanisms of premature labor and diabetes-associated birth defects, for instance, as well as new efforts to approach fetal surgery less invasively, are positioning us to both conquer our disappointments and achieve ambitious new moonshots.

The fetus as our patient

Fifty years ago, in 1966, a seminal paper in the Lancet reported that amniotic fluid cells could be cultured and were suitable for karyotyping (1[7434]:383-5). The tapping and examination of amniotic fluid had been reported on sporadically for many decades, for various clinical purposes, but by and large the fetal compartment was not invaded or directly examined. The fetus was instead the hopeful beneficiary of pregnancy care that focused on the mother. Fetal outcome was clouded in mystery, known only at birth.

With the Lancet report, prenatal detection of chromosomal disorders began to feel achievable, and the 1960s marked the beginning of a journey first through invasive methods of prenatal diagnosis and then through increasingly non-invasive approaches.

In 1970, just several years after the report on chromosome analysis of amniotic-fluid cells, another landmark paper in the New England Journal of Medicine described 162 amniocenteses performed between the 13th and 18th weeks of gestation and the detection of 10 cases of Down syndrome, as well as a few other cases of metabolic and other disorders (282[11]:596-9). This report provided an impetus for broader use of the procedure to detect neural tube defects, Down syndrome, and other abnormalities.

The adoption of amniocentesis for prenatal diagnosis still took some time, however. The procedure was used primarily early on to determine fetal lung maturity, and to predict the ability of the fetus to survive after delivery.

At the time, it was widely praised as an advanced method for evaluating the fetus. Yet, looking back, the early years of the procedure seem primitive. The procedure was done late in pregnancy and it was performed blindly, with the puncture site located either with external palpation of the uterus or with the assistance of static ultrasound. Patients who had scans would usually visit the radiologist, who would mark on the patient’s abdomen a suggested location for needle insertion. Upon the patient’s return, the obstetrician would then insert a needle into that spot, blindly and likely after the fetus had moved.

The development and adoption of real-time ultrasound was a revolutionary achievement. Ultrasound-guided amniocentesis was first described in 1972, 14 years after Ian Donald’s seminal paper introducing obstetric ultrasound was published in the Lancet (1958 Jun 7;1[7032]:1188-95).

As real-time ultrasound made its way into practice, it marked the true realization of a moonshot for obstetrics.

Not only could we simultaneously visualize the needle tip and place the needle safety, but we could see the real-time movement of the fetus, its activity, and the surrounding pockets of fluid. It was like looking up into the sky and seeing the stars for the first time. We could see fetal arrhythmia – not only hear it. With this window into the fetal compartment, we could visualize the fetal bowel migrating into the chest cavity due to a hole (hernia) in the diaphragm. We could visualize other malformations as well.

Chorionic villus sampling (CVS) was technically more difficult and took longer to evolve. For years, through the early 1980s, it was performed only at select centers throughout the country. Patients traveled for the procedure and faced relatively significant risks of complications.

By the end of the 1980s, however, with successive improvements in equipment and technique (including development of a transabdominal approach in addition to transvaginal) the procedure was deemed safe, effective, and acceptable for routine use. Fetoscopy, pioneered by John Hobbins, MD, and his colleagues at Yale University, New Haven, Conn., had also advanced and was being used to diagnose sickle cell anemia, Tay-Sachs disease, congenital fetal skin diseases, and other disorders.

With these advances and with our newfound ability to obtain and analyze a tissue sample earlier in pregnancy – even before a woman shared the news of her pregnancy, in some cases – it seemed that we had achieved our goals and may have even reached past the moon.

Yet there were other moonshots being pursued, including initiatives to make prenatal diagnosis less invasive. The discovery in 1997 of cell-free fetal DNA in maternal plasma and serum, for instance, was a pivotal development that opened the door for noninvasive prenatal testing.

This, and other advances in areas from biochemistry to ultrasound to genomic analysis, led to an array of prenatal diagnostic tools that today enable women and their physicians to assess the genetic, chromosomal, and biophysical aspects of their fetus considerably before the time of viability, and from both the maternal side and directly in the fetal compartment.

First-trimester screening is a current option, and we now have the ability to more selectively perform amniocentesis and CVS based on probability testing, and not solely on maternal age. Ultrasound technology now encompasses color Doppler, 3D and 4D imaging, and other techniques that can be used to assess the placenta, various structures inside the brain, and the heart, as well as blood flow through the ductus venosus.

Parents have called for and welcomed having the option of assessing the fetus in greater detail, and of having either assurance when anomalies are excluded or the opportunity to plan and make decisions when anomalies are detected.

Fetal surgery has been a natural extension of our unprecedented access to the fetus. Our ability to visualize malformations and their evolution led to animal studies that advanced our interest in arresting, correcting, or reversing fetal anomalies through in-utero interventions. In 1981, surgeons performed the first human open fetal surgery to correct congenital hydronephrosis.

Today, we can employ endoscopic laser ablation or laser coagulation to treat severe twin-to-twin syndrome, for instance, as well as other surgical techniques to repair defects such as congenital diaphragmatic hernia, lower urinary tract obstruction, and myelomeningocele. Such advances were unimaginable decades ago.

Old foes and new threats

Despite these advances in diagnosis and care, obstetrics faces unrealized moonshots – lingering challenges that, 50 years ago, we would have predicted would have been solved. Who would have thought that we would still have as high an infant mortality rate as we do, and that we would not be further along in solving the problem of prematurity? Our progress has been only incremental.

Fifty years ago, we lacked an understanding of the basic biology of preterm labor. Prematurity was viewed simply as term labor occurring too early, and many efforts were made over the years to halt the premature labor process through the use of various drugs and other therapeutics, with variable and minimally impactful levels of success.

In the last 25 years, and especially in the last decade, we have made greater efforts to better understand the biology of premature labor – to elucidate how and why it occurs – and we have come to understand that premature labor is very different physiologically from term labor.

Thanks to the work at the Perinatology Research Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), led by Roberto Romero, MD, attention has consequently shifted toward prediction, identification of women at highest risk, and prevention of the onset of premature labor among those deemed to be at highest risk.

Cervical length in the mid-trimester is now a well-verified predictor of preterm birth, and vaginal progesterone has been shown to benefit women without other known risk factors who are diagnosed with a shortened cervical length.

We have consequently seen the preterm birth rate decline a bit. In 2013, the last year for which we have complete data, the preterm birth rate dropped to 11.4%, down from a high of 12.8% in 2006, according to the Centers for Disease Control and Prevention.

Infant mortality similarly remains unacceptably high, due largely to the high preterm birth rate and to our failure to significantly alter the prevalence of birth defects. In 2010, according to the CDC, the infant mortality rate in the U.S. was 6.1 deaths per 1,000 live births (compared with 6.87 in 2005), and the United States ranked 26th in infant mortality among countries belonging to the Organisation for Economic Co-operation and Development, despite the fact that we spend a significant portion of our gross domestic product (17.5% in 2014) on health care.

Birth defects have taken over as a leading cause of infant mortality after early newborn life, and while we’ve made some advancements in understanding and diagnosing them, the majority of causes of birth defects are still unknown.

On the maternal side of obstetrical care, our progress has similarly been more modest than we have hoped for. Preeclampsia remains a problem, for instance. Despite decades of research into its pathogenesis, our advancements have been only incremental, and the condition – particularly its severe form – continues to be a vexing and high-risk problem.

Added to such age-old foes, moreover, are the growing threats of maternal obesity and diabetes, two closely related and often chronic conditions that affect not only the health of the mother but the in-utero environment and the health of the fetus. Today, more than one-third of all adults in the U.S., and 34% of women aged 20-39 years, are obese, and almost 10% of the U.S. population has diabetes.

Both conditions are on the rise, and obstetrics is confronting an epidemic of “diabesity” that would not necessarily have been predicted 50 years ago. It is particularly alarming given our growing knowledge of how obesity can be programmed in-utero and essentially passed on from generation to generation, of how diabetes can negatively affect perinatal outcomes, and of how the two conditions can have an additive effect on fetal complications.

Achieving new moonshots

Concerted efforts in the past several decades to step back and try to understand the basic biology and physiology of term labor and of premature labor have better positioned our specialty to achieve the moonshot of significantly reducing the incidence of preterm birth.

Establishment in the mid-1980s of the NICHD’s Perinatology Research Branch was a major development in this regard, helping to build and direct research efforts, including basic laboratory science, toward questions about what triggers and propagates labor. There has been notable progress in the past decade, in particular, and our specialty is now on the right path toward development of therapeutic interventions for preventing prematurity.

Additionally, the NICHD’s recently launched Human Placenta Project is building upon the branch-sponsored animal and cell culture model systems of the placenta to allow researchers, for the first time, to monitor human placental health in real time. By more fully understanding the role of the placenta in health and disease, we will be able to better evaluate pregnancy risks and improve pregnancy outcomes.

We also are learning through research in the University of Maryland Birth Defects Research Laboratory, which I am privileged to direct, and at other facilities, that maternal hyperglycemia is a teratogen, creating insults that can trigger a series of developmental fetal defects. By studying the biomolecular mechanisms of hyperglycemia-induced birth defects and developing “molecular maps,” we expect to be able to develop strategies for preventing or mitigating the development of such anomalies. I hope and expect that these future advancements, combined with reductions in prematurity, will significantly impact the infant mortality rate.

Fetal therapy and surgery will also continue to advance, with a much more minimally invasive approach taken in the next 50 years to addressing the fetal condition without putting the mother at increased risk. Just as surgery in other fields has moved from open laparotomy to minimally invasive techniques, I believe we will develop endoscopic or laparoscopic means of correcting the various problems in-utero, such as the repair of neural tube defects and diaphragmatic hernias. It already appears likely that a fetoscopic approach to treating myelomeningocele can reduce maternal morbidity while achieving infant neurological outcomes that are at least as good as outcomes achieved with open fetal surgery.

We’re in a much different position than we were 50 years ago in that we have two patients – the mother and the fetus – with whom we can closely work. We also have a relatively new and urgent obligation to place our attention not only on women’s reproductive health, but on the general gynecologic state. Ob.gyns. often are the only primary care physicians whom women see for routine care, and the quality of our attention to their weight and their diabetes risk factors will have far-reaching consequences, both for them and for their offspring.

As we have since the 1960s, we will continue to set new moonshots and meet new challenges, working with each other and with our patients to evaluate where we are strong and where we must improve. We will persistently harness the power of technology, choosing to do the things that “are hard,” while stepping back as needed to ask and address fundamental questions.

As a result, I can envision the next 50 years as a revolutionary time period for obstetrics – a time in which current problems and disorders are abated or eliminated through a combination of genomics, microbiomics, and other technological advances. Someday in the future, we will look back on some of our many achievements and marvel at how we have transformed the unimaginable to reality.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].

Select advances through the years

1960s

1965: Siemens Corp. introduces first real-time ultrasound scanner.

1966: Lancet paper reports that amniotic fluid cells can be cultured and karyotyped.

1970s

1970: New England Journal of Medicine paper describes mid-trimester amniocenteses and detection of Down syndrome cases.

1972: Ultrasound-guided amniocentesis first described.

1973: Fetoscopy introduced.

1980s

1981: First human open fetal surgery to correct congenital hydronephrosis.

Early 1980s: Chorionic villus sampling introduced at select centers.

1985: Color Doppler incorporated into ultrasound.

1990s

1990: Embryoscopy first described.

Mid-1990s: 3D/4D ultrasound begins to assume major role in ob.gyn. imaging.1997: Discovery of cell-free fetal DNA in maternal plasma.

2000s

2003: MOMS (Management of Myelomeningocele Study) was launched.

2010s

2012: The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine support cell-free DNA screening for women at increased risk of fetal aneuploidy.

2013: Preterm birth rate drops to 11.4%

2014: Diabetes incidence marks a 4-fold increase since 1980.

In 1961 before Congress, and in 1962 at Rice University, Houston, President John F. Kennedy called on America to land a man on the moon and bring him back safely, and to look beyond the moon as well, and pursue an ambitious space exploration program. He challenged the country to think and act boldly, telling Americans in his speech at Rice that “we choose to go the moon in this decade and do the other things, not because they are easy, but because they are hard.”

When Neil Armstrong and Buzz Aldrin set foot on the moon in 1969 – even before President Kennedy’s 10-year deadline had arrived – the country’s primary moonshot was realized. The President had inspired the nation, teams of engineers and others had collectively met daunting technological challenges, and space consequently was more open to us than ever before.

In looking at the field of obstetrics and how far it has come in the past 50 years, since the 1960s, it is similarly astonishing and inspiring to reflect on what extraordinary advances we have made. Who would have thought that the fetus would become such a visible and intimate patient – one who, like the mother, can be interrogated, monitored, and sometimes treated before birth? Who would have thought we would be utilizing genomic studies in a now well-established field of prenatal diagnosis, or that fetal therapy would become a field in and of itself?

Our specialty has advanced through a series of moonshots that have been inspired and driven by technological advancement and by our continually bold goals and vision for the health and well-being of women and their offspring. We have taken on ambitious challenges, achieved many goals, and embraced advancements in practice only to then set new targets that previously were unimaginable.

Yet just as our country’s space exploration program has faced disappointments, so has our field. It is sobering, for instance, that we have made only incremental improvements in prematurity and infant mortality, and that the age-old maternal problem of preeclampsia is still with us. We also face new challenges, such as the rising rate of maternal obesity and diabetes, which threaten both maternal and fetal health.

President Kennedy spoke of having “examined where we are strong, and where we are not.” Such self-reflection and assessment is a critical underpinning of advancement in fields across all of science, medicine, and health care, and in our specialty, it is a process that has driven ambitious new research efforts to improve fetal and maternal health.

A step back to more in-depth fundamental research on the biomolecular mechanisms of premature labor and diabetes-associated birth defects, for instance, as well as new efforts to approach fetal surgery less invasively, are positioning us to both conquer our disappointments and achieve ambitious new moonshots.

The fetus as our patient

Fifty years ago, in 1966, a seminal paper in the Lancet reported that amniotic fluid cells could be cultured and were suitable for karyotyping (1[7434]:383-5). The tapping and examination of amniotic fluid had been reported on sporadically for many decades, for various clinical purposes, but by and large the fetal compartment was not invaded or directly examined. The fetus was instead the hopeful beneficiary of pregnancy care that focused on the mother. Fetal outcome was clouded in mystery, known only at birth.

With the Lancet report, prenatal detection of chromosomal disorders began to feel achievable, and the 1960s marked the beginning of a journey first through invasive methods of prenatal diagnosis and then through increasingly non-invasive approaches.

In 1970, just several years after the report on chromosome analysis of amniotic-fluid cells, another landmark paper in the New England Journal of Medicine described 162 amniocenteses performed between the 13th and 18th weeks of gestation and the detection of 10 cases of Down syndrome, as well as a few other cases of metabolic and other disorders (282[11]:596-9). This report provided an impetus for broader use of the procedure to detect neural tube defects, Down syndrome, and other abnormalities.

The adoption of amniocentesis for prenatal diagnosis still took some time, however. The procedure was used primarily early on to determine fetal lung maturity, and to predict the ability of the fetus to survive after delivery.

At the time, it was widely praised as an advanced method for evaluating the fetus. Yet, looking back, the early years of the procedure seem primitive. The procedure was done late in pregnancy and it was performed blindly, with the puncture site located either with external palpation of the uterus or with the assistance of static ultrasound. Patients who had scans would usually visit the radiologist, who would mark on the patient’s abdomen a suggested location for needle insertion. Upon the patient’s return, the obstetrician would then insert a needle into that spot, blindly and likely after the fetus had moved.

The development and adoption of real-time ultrasound was a revolutionary achievement. Ultrasound-guided amniocentesis was first described in 1972, 14 years after Ian Donald’s seminal paper introducing obstetric ultrasound was published in the Lancet (1958 Jun 7;1[7032]:1188-95).

As real-time ultrasound made its way into practice, it marked the true realization of a moonshot for obstetrics.

Not only could we simultaneously visualize the needle tip and place the needle safety, but we could see the real-time movement of the fetus, its activity, and the surrounding pockets of fluid. It was like looking up into the sky and seeing the stars for the first time. We could see fetal arrhythmia – not only hear it. With this window into the fetal compartment, we could visualize the fetal bowel migrating into the chest cavity due to a hole (hernia) in the diaphragm. We could visualize other malformations as well.

Chorionic villus sampling (CVS) was technically more difficult and took longer to evolve. For years, through the early 1980s, it was performed only at select centers throughout the country. Patients traveled for the procedure and faced relatively significant risks of complications.

By the end of the 1980s, however, with successive improvements in equipment and technique (including development of a transabdominal approach in addition to transvaginal) the procedure was deemed safe, effective, and acceptable for routine use. Fetoscopy, pioneered by John Hobbins, MD, and his colleagues at Yale University, New Haven, Conn., had also advanced and was being used to diagnose sickle cell anemia, Tay-Sachs disease, congenital fetal skin diseases, and other disorders.

With these advances and with our newfound ability to obtain and analyze a tissue sample earlier in pregnancy – even before a woman shared the news of her pregnancy, in some cases – it seemed that we had achieved our goals and may have even reached past the moon.

Yet there were other moonshots being pursued, including initiatives to make prenatal diagnosis less invasive. The discovery in 1997 of cell-free fetal DNA in maternal plasma and serum, for instance, was a pivotal development that opened the door for noninvasive prenatal testing.

This, and other advances in areas from biochemistry to ultrasound to genomic analysis, led to an array of prenatal diagnostic tools that today enable women and their physicians to assess the genetic, chromosomal, and biophysical aspects of their fetus considerably before the time of viability, and from both the maternal side and directly in the fetal compartment.

First-trimester screening is a current option, and we now have the ability to more selectively perform amniocentesis and CVS based on probability testing, and not solely on maternal age. Ultrasound technology now encompasses color Doppler, 3D and 4D imaging, and other techniques that can be used to assess the placenta, various structures inside the brain, and the heart, as well as blood flow through the ductus venosus.

Parents have called for and welcomed having the option of assessing the fetus in greater detail, and of having either assurance when anomalies are excluded or the opportunity to plan and make decisions when anomalies are detected.

Fetal surgery has been a natural extension of our unprecedented access to the fetus. Our ability to visualize malformations and their evolution led to animal studies that advanced our interest in arresting, correcting, or reversing fetal anomalies through in-utero interventions. In 1981, surgeons performed the first human open fetal surgery to correct congenital hydronephrosis.

Today, we can employ endoscopic laser ablation or laser coagulation to treat severe twin-to-twin syndrome, for instance, as well as other surgical techniques to repair defects such as congenital diaphragmatic hernia, lower urinary tract obstruction, and myelomeningocele. Such advances were unimaginable decades ago.

Old foes and new threats

Despite these advances in diagnosis and care, obstetrics faces unrealized moonshots – lingering challenges that, 50 years ago, we would have predicted would have been solved. Who would have thought that we would still have as high an infant mortality rate as we do, and that we would not be further along in solving the problem of prematurity? Our progress has been only incremental.

Fifty years ago, we lacked an understanding of the basic biology of preterm labor. Prematurity was viewed simply as term labor occurring too early, and many efforts were made over the years to halt the premature labor process through the use of various drugs and other therapeutics, with variable and minimally impactful levels of success.

In the last 25 years, and especially in the last decade, we have made greater efforts to better understand the biology of premature labor – to elucidate how and why it occurs – and we have come to understand that premature labor is very different physiologically from term labor.

Thanks to the work at the Perinatology Research Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), led by Roberto Romero, MD, attention has consequently shifted toward prediction, identification of women at highest risk, and prevention of the onset of premature labor among those deemed to be at highest risk.

Cervical length in the mid-trimester is now a well-verified predictor of preterm birth, and vaginal progesterone has been shown to benefit women without other known risk factors who are diagnosed with a shortened cervical length.

We have consequently seen the preterm birth rate decline a bit. In 2013, the last year for which we have complete data, the preterm birth rate dropped to 11.4%, down from a high of 12.8% in 2006, according to the Centers for Disease Control and Prevention.

Infant mortality similarly remains unacceptably high, due largely to the high preterm birth rate and to our failure to significantly alter the prevalence of birth defects. In 2010, according to the CDC, the infant mortality rate in the U.S. was 6.1 deaths per 1,000 live births (compared with 6.87 in 2005), and the United States ranked 26th in infant mortality among countries belonging to the Organisation for Economic Co-operation and Development, despite the fact that we spend a significant portion of our gross domestic product (17.5% in 2014) on health care.

Birth defects have taken over as a leading cause of infant mortality after early newborn life, and while we’ve made some advancements in understanding and diagnosing them, the majority of causes of birth defects are still unknown.

On the maternal side of obstetrical care, our progress has similarly been more modest than we have hoped for. Preeclampsia remains a problem, for instance. Despite decades of research into its pathogenesis, our advancements have been only incremental, and the condition – particularly its severe form – continues to be a vexing and high-risk problem.

Added to such age-old foes, moreover, are the growing threats of maternal obesity and diabetes, two closely related and often chronic conditions that affect not only the health of the mother but the in-utero environment and the health of the fetus. Today, more than one-third of all adults in the U.S., and 34% of women aged 20-39 years, are obese, and almost 10% of the U.S. population has diabetes.

Both conditions are on the rise, and obstetrics is confronting an epidemic of “diabesity” that would not necessarily have been predicted 50 years ago. It is particularly alarming given our growing knowledge of how obesity can be programmed in-utero and essentially passed on from generation to generation, of how diabetes can negatively affect perinatal outcomes, and of how the two conditions can have an additive effect on fetal complications.

Achieving new moonshots

Concerted efforts in the past several decades to step back and try to understand the basic biology and physiology of term labor and of premature labor have better positioned our specialty to achieve the moonshot of significantly reducing the incidence of preterm birth.

Establishment in the mid-1980s of the NICHD’s Perinatology Research Branch was a major development in this regard, helping to build and direct research efforts, including basic laboratory science, toward questions about what triggers and propagates labor. There has been notable progress in the past decade, in particular, and our specialty is now on the right path toward development of therapeutic interventions for preventing prematurity.

Additionally, the NICHD’s recently launched Human Placenta Project is building upon the branch-sponsored animal and cell culture model systems of the placenta to allow researchers, for the first time, to monitor human placental health in real time. By more fully understanding the role of the placenta in health and disease, we will be able to better evaluate pregnancy risks and improve pregnancy outcomes.

We also are learning through research in the University of Maryland Birth Defects Research Laboratory, which I am privileged to direct, and at other facilities, that maternal hyperglycemia is a teratogen, creating insults that can trigger a series of developmental fetal defects. By studying the biomolecular mechanisms of hyperglycemia-induced birth defects and developing “molecular maps,” we expect to be able to develop strategies for preventing or mitigating the development of such anomalies. I hope and expect that these future advancements, combined with reductions in prematurity, will significantly impact the infant mortality rate.

Fetal therapy and surgery will also continue to advance, with a much more minimally invasive approach taken in the next 50 years to addressing the fetal condition without putting the mother at increased risk. Just as surgery in other fields has moved from open laparotomy to minimally invasive techniques, I believe we will develop endoscopic or laparoscopic means of correcting the various problems in-utero, such as the repair of neural tube defects and diaphragmatic hernias. It already appears likely that a fetoscopic approach to treating myelomeningocele can reduce maternal morbidity while achieving infant neurological outcomes that are at least as good as outcomes achieved with open fetal surgery.

We’re in a much different position than we were 50 years ago in that we have two patients – the mother and the fetus – with whom we can closely work. We also have a relatively new and urgent obligation to place our attention not only on women’s reproductive health, but on the general gynecologic state. Ob.gyns. often are the only primary care physicians whom women see for routine care, and the quality of our attention to their weight and their diabetes risk factors will have far-reaching consequences, both for them and for their offspring.

As we have since the 1960s, we will continue to set new moonshots and meet new challenges, working with each other and with our patients to evaluate where we are strong and where we must improve. We will persistently harness the power of technology, choosing to do the things that “are hard,” while stepping back as needed to ask and address fundamental questions.

As a result, I can envision the next 50 years as a revolutionary time period for obstetrics – a time in which current problems and disorders are abated or eliminated through a combination of genomics, microbiomics, and other technological advances. Someday in the future, we will look back on some of our many achievements and marvel at how we have transformed the unimaginable to reality.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].

Select advances through the years

1960s

1965: Siemens Corp. introduces first real-time ultrasound scanner.

1966: Lancet paper reports that amniotic fluid cells can be cultured and karyotyped.

1970s

1970: New England Journal of Medicine paper describes mid-trimester amniocenteses and detection of Down syndrome cases.

1972: Ultrasound-guided amniocentesis first described.

1973: Fetoscopy introduced.

1980s

1981: First human open fetal surgery to correct congenital hydronephrosis.

Early 1980s: Chorionic villus sampling introduced at select centers.

1985: Color Doppler incorporated into ultrasound.

1990s

1990: Embryoscopy first described.

Mid-1990s: 3D/4D ultrasound begins to assume major role in ob.gyn. imaging.1997: Discovery of cell-free fetal DNA in maternal plasma.

2000s

2003: MOMS (Management of Myelomeningocele Study) was launched.

2010s

2012: The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine support cell-free DNA screening for women at increased risk of fetal aneuploidy.

2013: Preterm birth rate drops to 11.4%

2014: Diabetes incidence marks a 4-fold increase since 1980.

Why is your geriatric patient whose life seemed fulfilling before retirement now talking about not feeling “right”? “Am I depressed, or is this normal,” your patient wants to know. What should be your reply, and what interventions can you take to help this patient in the context of a 15-minute appointment?

In this video, part of the Mental Health Consult series of roundtable discussions, our panel members discuss their recommendations for work-up and next steps for managing a 65-year-old recently retired man with a history of prostate cancer but no psychiatric disorders. He has some mild depressive symptoms, and he brings up suicide during the office visit.

Join our panel of experts from George Washington University, Washington, including Katalin Roth, MD, director of geriatrics and palliative medicine; April Barbour, MD, director of the division of general internal medicine; and Lorenzo Norris, MD, medical director of psychiatric and behavioral services, as they discuss how to differentiate between the distress often inherent in life passages and mental illness, and how practice models drive treatment decisions and reimbursement.

[email protected]

On Twitter @whitneymcknight

Why is your geriatric patient whose life seemed fulfilling before retirement now talking about not feeling “right”? “Am I depressed, or is this normal,” your patient wants to know. What should be your reply, and what interventions can you take to help this patient in the context of a 15-minute appointment?

In this video, part of the Mental Health Consult series of roundtable discussions, our panel members discuss their recommendations for work-up and next steps for managing a 65-year-old recently retired man with a history of prostate cancer but no psychiatric disorders. He has some mild depressive symptoms, and he brings up suicide during the office visit.

Join our panel of experts from George Washington University, Washington, including Katalin Roth, MD, director of geriatrics and palliative medicine; April Barbour, MD, director of the division of general internal medicine; and Lorenzo Norris, MD, medical director of psychiatric and behavioral services, as they discuss how to differentiate between the distress often inherent in life passages and mental illness, and how practice models drive treatment decisions and reimbursement.

[email protected]

On Twitter @whitneymcknight

Why is your geriatric patient whose life seemed fulfilling before retirement now talking about not feeling “right”? “Am I depressed, or is this normal,” your patient wants to know. What should be your reply, and what interventions can you take to help this patient in the context of a 15-minute appointment?

In this video, part of the Mental Health Consult series of roundtable discussions, our panel members discuss their recommendations for work-up and next steps for managing a 65-year-old recently retired man with a history of prostate cancer but no psychiatric disorders. He has some mild depressive symptoms, and he brings up suicide during the office visit.

Join our panel of experts from George Washington University, Washington, including Katalin Roth, MD, director of geriatrics and palliative medicine; April Barbour, MD, director of the division of general internal medicine; and Lorenzo Norris, MD, medical director of psychiatric and behavioral services, as they discuss how to differentiate between the distress often inherent in life passages and mental illness, and how practice models drive treatment decisions and reimbursement.

[email protected]

On Twitter @whitneymcknight

If you are a veteran PA or a PA on active duty in the uniformed services, you may want to take advantage of the PA History Society’s plans to upgrade the Veteran Memorial Garden at the Eugene A. Stead, Jr, Center for Physician Assistants in Durham, North Carolina, into a “place of remembrance.”

The Society is selling 9 x 9-in engraved brick pavers for $100 each. For those interested in purchasing more than one paver, they are offering a sliding scale: 1 for $100, 2 for $175, 3 for $250, 4 for $325, and 5 for $400. The engraved paver will include the appropriate uniformed service logo and 3 lines for name, branch, and years of service. The pavers will be embedded in the wheelchair accessible walkway and in the patio area surrounding a life-size bronze combat medic statue— the centerpiece of the garden.

This is a chance to honor yourself and other PA colleagues who have served or are currently serving their country. Construction and landscaping is to begin in October 2016, with a dedication ceremony scheduled for April 2017.

Order now via the Society’s website at http://pahx.org/ to make sure that your paver is displayed prominently in the garden.

Reginald Carter, PhD, PA
Historian Emeritus
PA History Society

If you are a veteran PA or a PA on active duty in the uniformed services, you may want to take advantage of the PA History Society’s plans to upgrade the Veteran Memorial Garden at the Eugene A. Stead, Jr, Center for Physician Assistants in Durham, North Carolina, into a “place of remembrance.”

The Society is selling 9 x 9-in engraved brick pavers for $100 each. For those interested in purchasing more than one paver, they are offering a sliding scale: 1 for $100, 2 for $175, 3 for $250, 4 for $325, and 5 for $400. The engraved paver will include the appropriate uniformed service logo and 3 lines for name, branch, and years of service. The pavers will be embedded in the wheelchair accessible walkway and in the patio area surrounding a life-size bronze combat medic statue— the centerpiece of the garden.

This is a chance to honor yourself and other PA colleagues who have served or are currently serving their country. Construction and landscaping is to begin in October 2016, with a dedication ceremony scheduled for April 2017.

Order now via the Society’s website at http://pahx.org/ to make sure that your paver is displayed prominently in the garden.

Reginald Carter, PhD, PA
Historian Emeritus
PA History Society

If you are a veteran PA or a PA on active duty in the uniformed services, you may want to take advantage of the PA History Society’s plans to upgrade the Veteran Memorial Garden at the Eugene A. Stead, Jr, Center for Physician Assistants in Durham, North Carolina, into a “place of remembrance.”

The Society is selling 9 x 9-in engraved brick pavers for $100 each. For those interested in purchasing more than one paver, they are offering a sliding scale: 1 for $100, 2 for $175, 3 for $250, 4 for $325, and 5 for $400. The engraved paver will include the appropriate uniformed service logo and 3 lines for name, branch, and years of service. The pavers will be embedded in the wheelchair accessible walkway and in the patio area surrounding a life-size bronze combat medic statue— the centerpiece of the garden.

This is a chance to honor yourself and other PA colleagues who have served or are currently serving their country. Construction and landscaping is to begin in October 2016, with a dedication ceremony scheduled for April 2017.

Order now via the Society’s website at http://pahx.org/ to make sure that your paver is displayed prominently in the garden.

Reginald Carter, PhD, PA
Historian Emeritus
PA History Society