0:02

This is Thinking About OBGYN

0:04

with your hosts Antonia Roberts

0:07

and Howard Harrell .

0:18

Antonia .

0:19

Howard .

0:20

What are we thinking about on today's episode ?

0:22

Well , we're going to get into part two

0:24

of our attempt at giving advice

0:26

on how to read journal articles properly

0:29

, and we're going to talk about some example

0:32

papers today involving a

0:34

study on elegolics , another

0:36

one on intranasal metaclopramide

0:39

or a version of reglain , and

0:41

another one on a virtual doula

0:43

service . But first , what's the thing

0:45

we do without evidence ?

0:47

Well , how about placing oxygen on

0:49

a mother when there's a problem with a fetal

0:51

tracing or some decelerations or something

0:53

like that that we're anxious about ?

0:55

Okay , sure , yeah , I've seen this

0:57

a lot in my time so far . I

1:00

think at some point almost all of us

1:02

have probably been taught that part

1:04

of intrapartum fetal resuscitation

1:06

for decelerations on the monitor

1:08

or other issues with CAT2

1:11

or CAT3 tracings would be oxygen

1:13

supplementation . So frequently

1:15

nurses will place a non-rebrether mask

1:18

on the mother and crank up the oxygen

1:20

as part of this general approach to

1:22

resuscitation . That might also include

1:24

position changes or fluid

1:26

boluses or stopping the pitocin

1:28

, giving her butylene , maybe starting an amniote

1:31

fusion and other such attempts

1:33

to clean up the fetal tracing . But

1:35

why don't you tell us why the oxygen mask

1:38

is a thing we do without evidence ?

1:40

Well , it's not that we should never do it or that there's

1:42

that it's never the right thing

1:45

to do . It's just that it isn't beneficial

1:47

in most cases and might even be

1:49

harmful if the mother herself

1:51

isn't hypoxic . So I think we

1:54

get caught up in just applying all of our

1:56

interventions that we have available to us for

1:58

abnormal or indeterminate fetal tracings

2:00

to every patient that has one all

2:02

at once , hoping that something sticks . Essentially

2:05

so , as you said , this might be a fluid bolus

2:07

and position change , and turning the oxytocin

2:10

off or , this case , throwing some

2:12

oxygen on the mom and hoping

2:14

that it straightens up . And there's

2:16

some sense to that , because we don't usually

2:19

know in many cases the specific

2:21

reason why we're seeing , let's say

2:23

, repetitive late decelerations or something like

2:25

that , and therefore what the specific remedy

2:27

might be . And there's simply no

2:30

reason , though , in this case , to give

2:32

an oxygen , give oxygen supplementation

2:34

to a mother who's already

2:36

saturating . Well , we know what her oxygen saturation

2:38

is and there's no benefit in adding

2:41

oxygen to her .

2:42

Most of the time women in labor have a

2:44

continuous pulse axon . It's , that's

2:46

just normal and , yeah

2:49

, giving her oxygen would definitely be appropriate

2:51

if she had true low oxygen

2:53

saturation , so usually something

2:56

below 94% . Maybe she has

2:58

asthma or maybe she's preeclampic

3:01

and has pulmonary edema , or maybe

3:03

she has a respiratory illness like flu or COVID

3:05

or something like that , and in those cases

3:08

the fetal distress and the heart

3:10

rate abnormalities that we see

3:12

on the monitor could definitely be from

3:14

fetal hypoxemia or hypoxia

3:17

due to maternal

3:19

hypoxia , which would be

3:21

a lack of oxygen tension in her blood

3:23

. So obviously we should treat that underlying

3:25

cause . But for a normally

3:28

oxygenating mother who still has

3:30

fetal heart rate abnormalities , it's usually

3:32

not something that adding

3:35

extra oxygen would fix . There's

3:37

usually some completely unrelated cause

3:39

, like chord compression or utero

3:41

placental insufficiency , for example

3:44

. So super oxygenating her

3:46

in those cases is just not

3:48

effective at getting more oxygen

3:50

to the fetus .

3:51

Hickhog , practice Bolton 106 talks

3:53

about oxygen supplementation frequently

3:56

being used despite any adequate

3:58

data to support the practice . But they've actually

4:00

updated this in the last couple of years to say

4:02

definitively that there is no

4:04

evidence of benefit from oxygen supplementation

4:07

. The update to the Practice Bolton

4:09

says that the routine use of oxygen

4:11

in women who have normal saturations

4:13

is not recommended .

4:15

Yeah , and that update came after a systematic

4:17

review is published of 16

4:20

trials that evaluated this practice

4:22

in 2052

4:24

women , and they found no difference in umbilical

4:26

artery pH or neonatal

4:29

asidemia or NICU admission rates

4:31

or any other clinical outcome .

4:33

There was also a study published in the Gray Journal

4:35

in 2020 that gave us the results

4:37

of a trial in which women at term with

4:39

category two tracings in labor were

4:42

randomized to 10 liters of oxygen with

4:44

a face mask versus just room air

4:46

. The intervention group wore the oxygen

4:48

mask continually until they delivered and

4:50

they looked at a lot of different outcomes , including what

4:53

the tracings look like and different characteristics

4:55

of the tracing . They found that for the patients

4:57

who received oxygen , there was no difference

4:59

in the features of the fetal monitor pre

5:01

and post randomization and there was no

5:03

difference in the time to resolve

5:06

the decelerations or whatever was abnormal

5:08

between the two groups of patients of

5:11

room air versus the oxygen supplementation

5:13

. So that adds to the systematic

5:15

review you just mentioned , which showed no

5:17

improvement in objective measures about

5:19

the newborns and no improvements

5:21

in the fetal tracings themselves .

5:23

So , yeah , no clinical effects at all . Awon

5:26

, which is the Association of Women's

5:28

Health , obstetric and Neonatal Nurses , also

5:31

released a statement in March 2022

5:33

and this was somewhat of a response

5:36

to that ACOG practice advisory

5:38

which is brought up . They reviewed

5:40

literature up until that point , just like ACOG

5:42

had , and interestingly

5:45

, they did acknowledge that it hasn't

5:47

been shown to benefit . But

5:49

they essentially wanted

5:51

to caution against swinging too far the

5:53

other way , thinking that the

5:55

downside would be people would never

5:57

, ever , ever use oxygen for intrauterine resuscitation

6:00

. So they in their statement

6:02

recommend keeping it as an option

6:04

for use in some patients who

6:07

didn't improve despite all the other

6:09

measures being used . And basically they

6:11

said don't use it as a first line , but keep it

6:13

in mind as maybe a second or

6:15

third line . I'm not sure if they're

6:17

thinking that that category of

6:19

patients who haven't responded maybe

6:22

include people who actually are

6:24

desatting , actually are in respiratory compromise

6:26

, and we don't realize it and

6:28

so we're just thinking well , maybe

6:30

they , maybe we're having a false positive

6:33

normal oxygen on this false ox , or maybe

6:35

we don't have the false ox on or

6:37

something like that . If it's slipped off sometimes

6:40

it slips off in labor . That

6:42

could happen , but I think this

6:44

can fall into that slippery slope of something

6:47

that we do without evidence

6:49

of benefit , despite that adequate trials

6:51

. Because if we want to

6:53

do something and we wonder , well , we've

6:56

done all these other things , the tracing is still

6:58

bad . What harm could it be now to

7:00

put oxygen on the mother ? Just throw it on

7:02

? It's just oxygen . Maybe it might

7:04

help this individual patient for some reason .

7:06

Sure , yeah , A lot of the things we talk about on

7:08

here . But I think that that can be a dangerous

7:11

way of thinking . In my view , A1

7:13

is clearly wrong about this and

7:15

they issued this response , as you said , to the ACOG

7:17

bulletin in a sort of contentious way

7:20

. It's a pattern we've seen over and over

7:22

again . It's why things like tokylysis

7:24

or progesterone therapy for various

7:26

conditions or whatever , has persisted

7:28

for so long because a lot of folks

7:31

in they have a paradigm

7:33

in their mind that doesn't use a scientific method

7:35

to make decisions . But that's also the

7:37

lesson , for example , of DES

7:39

. It doesn't matter if you think that something might

7:41

work by some mechanism for some

7:43

individual patient . You have to prove

7:46

that it does work and reserve

7:48

utilization of something , an agent

7:50

or intervention , until there are replicated

7:52

trials that show that something is effective . It's

7:55

easy to say but what's the harm , especially with

7:57

oxygen or something like that ? But again

7:59

, that was the lesson of DES . The harm of DES

8:01

wasn't even seen for decades to come , just

8:03

as a potential harm of 17-hydroxyprogesterone

8:07

wasn't seen until we've started

8:09

to see some evidence that the offspring of children

8:11

exposed to it , at least in earlier gestational

8:13

ages , might have a higher rate of cancer

8:15

as adults . So in the absence of a proven benefit

8:18

, we should not use therapies .

8:20

Yeah , and we do know that , for example

8:22

, in neonates , hyperoxygenating

8:25

them with their various

8:27

resuscitation situation , that's

8:29

harmful and they try to recommend dialing

8:31

it down as soon as you can . So

8:34

some people have speculated that even

8:36

maternal oxygen might be

8:38

harmful to the fetus , right , right

8:40

?

8:41

yeah , well , I'll put a link to a great

8:43

review article of this literature

8:45

and the science that was published in 2023,

8:47

. But they do discuss potential harms

8:49

and the concept here is that free radical-induced

8:52

oxidative cell damage can contribute to

8:54

adverse outcomes , including necrotizing intercollitis

8:57

and bronchopulmonary dysplasia , and they

8:59

cite literature that says that resuscitation

9:01

with room air as opposed to 100%

9:03

oxygen with a rebreather face

9:05

mask is associated with less-needle

9:08

harm , including hypoxic ischemic encephalopathy

9:11

and death . In other words , room air is better . This

9:13

has been studied in more extensively

9:15

in animal models , where some of the

9:17

basic sciences of how this may work

9:19

has been elucidated , and they go into this

9:21

literature in some detail . But again , the point

9:24

is that every intervention , even oxygen

9:26

, potentially has harm . We actually

9:28

understand and have some evidence that

9:30

this practice is potentially harmful and

9:33

, on the flip side , we have no evidence

9:35

from multiple trials now that it benefits

9:37

newborns in any way or that

9:39

it makes the tracing look better in any way

9:41

. So the practice should be abandoned

9:43

and ACOG is right .

9:45

So , in summary , people want to

9:47

do something in scary situations , but every

9:49

intervention is also potentially

9:51

harmful , so even the most innocuous

9:54

sounding things like an oxygen mask

9:56

should only be done if we know they're effective

9:58

.

9:58

That's a lesson of our whole podcast . Yeah .

10:00

Yeah , that sums it all up . Okay

10:03

, let's get into part two of talking

10:05

about interpreting papers and

10:07

studies . This time , we want

10:09

to take some of the things we already discussed

10:11

last time and look at a few papers

10:13

briefly , using these skills , and

10:16

we also want to answer about

10:18

how to approach , whether we should adopt something

10:20

into practice or not , because I think that's

10:23

where bias can tend to drive us towards

10:25

making these decisions more so than

10:27

the evidence , and bias

10:29

can come internally from our own desires

10:31

to help people , but also externally

10:33

, from the companies that are selling

10:35

the intervention and also

10:38

, maybe , the charismatic personalities

10:40

who are representing these companies

10:42

and driving our thought processes

10:45

, sometimes counter to evidence .

10:46

Or even just our own , as you said with the oxygen , our

10:49

own internal desire to do something

10:51

, and we ignore scientific literature

10:53

.

10:53

Yeah , all right . So what

10:55

was the first article you wanted to talk

10:57

about ?

10:58

Well , I want to highlight a real life example

11:00

of deciding whether you should adopt

11:02

something into practice . So this

11:05

happens to all of us , maybe

11:07

on a daily or weekly basis . So my clinic

11:09

was recently visited by a pharmaceutical

11:11

rep we don't normally allow them , but

11:13

we can't stop them from walking up to the front

11:15

door and they brought some information , in a summary

11:17

of a clinical trial , about a new product

11:19

called Gemodi . Now this is a

11:22

metaclopramide nasal spray that's

11:24

FDA indicated for the relief of symptoms

11:26

in adults with acute and recurrent diabetic

11:29

gastroparesis .

11:30

Okay , well , acute and recurrent diabetic

11:33

gastroparesis is not my

11:35

bread and butter , it's an OBGYN

11:37

. I don't know about you .

11:39

Well , I am diabetic , but it's

11:41

not uncommon for drug reps to come by

11:43

trying to cast a wide net for

11:46

their products , hoping to catch all sorts of

11:48

providers that might possibly encounter

11:50

the drugs target patient population . But

11:52

I'm pretty sure this rep was primarily trying

11:54

to push it as an off-label use

11:56

for nausea and vomiting .

11:58

I haven't seen this particular product

12:00

in my clinic lounge , but I have

12:03

walked in there at lunch and

12:05

encountered reps that are trying to talk

12:07

to me about migraine meds that

12:09

are specifically not meant for pregnant

12:11

patients , so definitely not relevant

12:13

for me , and also things like heart failure meds

12:16

, definitely out of my scope , and

12:18

some of those obviously were a

12:20

stretch in terms of their relevance . But if

12:22

I had to guess for Gemodi

12:25

at your clinic , I imagine you were being

12:27

shown this because you

12:29

sometimes use oral metaclopramide

12:32

, or Reglan is the trade name we

12:34

use for nausea and vomiting during pregnancy

12:36

, right ?

12:37

Yeah , absolutely . And there was , I'll

12:39

say , a sticky note attached to this

12:41

information that said . Quote

12:43

new for nausea , for nausea

12:45

.

12:46

Okay , well , so it sounds

12:48

like they weren't actually stopping

12:51

by to offer you health and treating

12:53

the diabetic gastroparesis at

12:55

all . So did you talk to this rep ?

12:58

No , I don't talk to them . I actually don't know who they

13:00

were . It was just left for us because

13:02

we don't normally engage with drug reps in

13:04

my office .

13:05

Okay , that's probably a good policy . Well

13:07

, that's good because I hope they know

13:09

it's actually illegal to promote

13:12

or advertise using a drug or

13:14

device for anything other than its

13:16

FDA approved use . So legally

13:18

that would be called misbranding

13:20

.

13:20

Well , it is illegal , but it happens a

13:22

lot and in various shades

13:24

of gray , and in some cases we've seen

13:27

some high-profile settlements where companies

13:29

have paid fines for doing exactly this

13:31

. But nevertheless it continues , and often

13:34

in subtle ways that you might not realize

13:36

. Sometimes the reps will talk about

13:38

another doctor they know at another

13:40

insert big name clinic who's

13:42

seeing great results with using drug

13:44

whatever for off-label indication

13:46

whatever . But that's not scientific information

13:49

and it's not studied for those off-label

13:51

uses for safety and efficacy . They just hope

13:53

that you'll use it because whoever they

13:55

name drop seems like an important person

13:58

to you , because they work at wherever

14:00

, and I may not mention that those

14:02

folks are stock owners of the company or

14:04

that they're paid by the company

14:07

to do talks for them or as a consultant or

14:09

something like that .

14:10

Okay . Well , with your example here , it

14:12

sounds like we're already off to a sketchy start

14:14

, but let's go through the processes

14:16

we talked about last time for

14:18

adopting something to practice or not .

14:20

Well , in this case , if I were going to use this

14:23

intranasal version of regland for

14:25

nausea and vomiting during pregnancy

14:27

or any other kind of nausea that

14:29

maybe I would treat like post-op nausea

14:31

or migraines in pregnancy we sometimes

14:33

use regland for , or even symptoms

14:36

of , chronic pelvic pain or premastrial

14:38

dyscort disorder . I would want to see first

14:40

a randomized controlled blinded

14:42

trial that placebo controlled trial

14:44

that showed that the drug was better than

14:47

placebo for treatment of nausea

14:49

and vomiting in that specific population

14:51

and that it made a difference in some outcome

14:53

. That was important to my patient .

14:55

Yeah , so a drug that's been

14:57

indicated and approved for gastroparesis

15:00

is not going to have those kinds

15:02

of studies yet . But the FDA normally

15:05

would require two studies like

15:07

that before they give their approval

15:09

for the drug and for

15:11

the indication in question . We do

15:13

use drugs off label all the time

15:16

because many studies are

15:18

actually done after the FDA

15:20

approval to guide that use . So

15:22

you know , side attack for labor

15:24

induction for example . It's just that

15:26

the drug reps cannot be

15:29

the ones to push that off label

15:31

use of it . They can't be like selling

15:33

you the drug with primarily for this non

15:36

FDA approved indication . So

15:38

were there any studies done

15:40

for this intranasal drug in

15:42

pregnant or gynecologic patients

15:44

, perhaps after the FDA approval

15:46

?

15:47

Not a single one . So the nice thing is we

15:49

get to skip the whole study part that we talked

15:51

about in the last episode , because there aren't studies .

15:53

So this was a trick . Are we going to do

15:55

the five step process at all

15:57

today ?

15:59

Well , we don't want to be too redundant , but I think if this

16:01

more is a public service announcement , this is real

16:03

life . This is just something that actually happened

16:05

If my office was visited by

16:07

a rep suggesting an off label and unstudied

16:09

use of their drug . I bet a lot of our

16:12

listeners might be caught

16:14

off guard by that as well as I was , and

16:16

their initial reaction to something

16:18

like this intranasal metaclopramide

16:20

at least , might just be that , oh

16:22

great , it's nice that we have another form of this drug

16:25

that we already use frequently , especially

16:27

a non oral drug for these patients who are really

16:29

nauseous , so then they can't hold down pills

16:32

. But my point is , if there isn't even

16:34

a good paper or a paper

16:36

to do the five step process on

16:38

, that should be a huge red flag

16:40

, and this happens a lot .

16:41

Okay , yeah , and one might reasonably

16:43

assume that if a company is coming to

16:46

visit your clinic and promote their drug

16:48

, that they would have that

16:50

the drug already would have the FDA approval

16:52

for what they're talking to you about , but apparently

16:55

not . So apparently you have to trust

16:57

trust no one and

16:59

always fact check them .

17:01

Trust , don't trust and verify right

17:03

.

17:03

Right .

17:04

Well , but it's actually not even enough to

17:06

have the two randomized placebo

17:08

controlled trials that might lead to an FDA

17:11

indication . I would suggest that's a minimum

17:13

threshold before adopting a new intervention into

17:15

practice . But we need more than that . Next

17:18

we need a comparator trial .

17:20

Okay , yeah , we've talked about how

17:22

interesting it is that we think of the

17:24

placebo controlled RCT as a gold standard

17:27

, and it is for showing safety

17:29

and efficacy , but it is not the

17:31

gold standard for determining whether

17:33

or not we adopt something into practice .

17:35

Right , exactly , so what actually changes

17:37

our practice pattern would be a trial that

17:39

shows that this new therapy

17:41

is better than what we're

17:44

currently using or safer than what we're

17:46

currently using . So before I consider

17:48

using a medication we talked about this was Zaranolone

17:51

, for example I would want to see a head

17:53

to head trial that showed that it was better

17:55

again in some meaningful outcome

17:58

for my patient , than

18:00

any of the other number of things that I currently

18:02

use . So in this case , for nausea , vomiting , that

18:04

might be things like vitamin B six or doc

18:06

salamine , or on Danzatron or anything

18:09

else that we might use .

18:10

Okay . So to recap , if we're considering

18:12

adopting something into clinical practice

18:14

, first we need to know that two at

18:17

least two quality replicated

18:19

RCTs against placebo have

18:21

been done that show the benefit

18:24

and the safety . And then we need to

18:26

see at least one quality

18:28

comparator trial that shows that it

18:30

is superior in some meaningful way

18:32

to what we're already doing

18:34

. And is that it ?

18:36

Well , almost . We still then

18:39

need some information , formally

18:41

or informally , for a cost-benefit analysis

18:44

. So it's tempting to think that

18:46

I could give a patient regland through a nasal

18:48

spray who's vomiting and can't keep a pill

18:50

down , and that'll be the instinct

18:53

, I think , of a lot of OJYans who come

18:55

up on this drug after being visited by

18:57

this rep . Now , keep in mind that

18:59

that instinct is wrong because we skipped over

19:02

those first two important steps you

19:04

just recapped . But let's think about the third

19:06

step . If we got there , if the other study

19:08

showed that , yes , it's effective for nausea , it

19:10

probably is right . I don't doubt it . And yes

19:12

, it works better than , I don't know , vitamin

19:15

B6 or something . Well , the thing is

19:17

, this medication costs $2,300

19:20

for what looks like a one-month

19:22

supply .

19:23

Okay , yikes , yeah , okay , just

19:25

for comparison , almost everything

19:28

else we use is gonna be available

19:30

for under 10 bucks or

19:32

something much cheaper than $2,300

19:36

. So that would definitely require a

19:38

lot of justification .

19:39

Yeah , related to this . A good example of

19:42

this thought process would be the combination

19:44

vitamin B6 and doxalamine

19:46

tablets that are available in

19:49

the form of DiClegis or Bongesta

19:51

. So these medications , initially

19:53

at least , were priced at over $600

19:56

when they came to market and even with

19:58

steep discounting and reductions over time

20:00

that have occurred , it's still over $200

20:03

a month today , with an average pregnant

20:05

patient using these drugs for two to three months

20:07

in the first part of the pregnancy . Now the combination

20:09

of vitamin B6 and doxalamine

20:12

does work better than placebo and

20:14

, frankly , it works better and preferentially

20:16

over many of the other anti-imetics

20:19

that we just mentioned . But again , when we get

20:21

to the last point , vitamin B6

20:23

and doxalamine are both over-the-counter

20:25

products that can be purchased

20:28

separately , and the combination

20:30

for a month supply is less than 10 bucks . So

20:32

there's no compelling reason to

20:34

prescribe one of the trademark combo medications

20:37

that are $600 .

20:39

Yeah , so drug companies love

20:42

to take inexpensive drugs and then

20:44

find some new delivery method or some

20:46

new feature that they can put

20:48

their little trademark on or patent

20:50

on or something , and that would extend the

20:52

patent life and makes it see , maybe

20:54

slightly more convenient or

20:57

better in some way . Like they could

20:59

, instead of combining two separate drugs

21:01

, they could come out with an extended release

21:03

version that you only give once

21:06

a day instead of twice a day , but then

21:08

that extended release is like 10 times

21:10

more expensive . So it seems like a great

21:12

thing to give to your patient until you realize how

21:14

much more it costs them . And just in

21:16

the grand scheme like that , we're

21:18

bankrupting healthcare with these sorts

21:20

of lazy shortcuts .

21:23

Yeah , it's a very American thing too , okay

21:25

. Well , let's move on to elagolics , and

21:27

we've not really talked about this drug yet

21:29

, but it is being heavily marketed right now

21:31

in our field .

21:33

Yeah , I first heard about this in residency

21:35

. It's called Oralisa

21:38

is one of the trade names , and Oralisa

21:40

is $1,200 a month . So

21:43

this is an oral GNRH antagonist

21:45

which is approved for

21:47

treatment of pain related to endometriosis

21:50

, and it's also marketed

21:52

in the form of a combination

21:54

that contains ad-bac hormones

21:56

, so you can get it just separately , with

21:59

only the antagonists or with

22:01

estrogen and progestin . So

22:03

this went through the process . You would expect to

22:05

get the FDA approval . These were the

22:08

LRS endometriosis

22:10

one and two trials . In those trials

22:12

, roughly 20% of women reported

22:14

improvement in their dysmenorrhea symptoms with

22:16

placebo , compared to

22:19

45 and 75%

22:22

respectively , reporting improvement with

22:24

the low dose versus the high dose

22:26

versions of this drug .

22:28

Right and this led to FDA approval . And

22:30

of course we could go and look at those individual

22:33

studies in detail and go through the questions

22:35

we talked about in the last episode , and

22:37

if we did we would discover that the

22:39

trial design and the statistical methods

22:41

were appropriate . We can pick

22:43

at NATs a little bit , but these studies were designed

22:46

obviously by the company and so sure

22:48

there's a chance of some bias . But

22:50

the magnitude of effect was significant enough and

22:52

it's consistent with what we would expect from what

22:55

we know about how this medication should

22:57

work and how the pathophysiology

22:59

of dysmenorrhea and endometriosis and et

23:01

cetera . So I don't doubt that this medication

23:04

is highly effective compared to placebo

23:06

. Remember that initial studies

23:08

performed by a company , though , do tend to report

23:11

an effect size that's roughly double

23:13

what later studies may show that

23:15

don't have the bias of being designed

23:17

by the company , but I do think we

23:19

can agree that this medicine is superior

23:22

to placebo for treatment of endometriosis

23:24

.

23:25

Right , it's not like we just ignore studies if they

23:27

were funded by the companies and

23:29

haven't been replicated yet , but we

23:31

interpret them with caution and then proceed

23:33

while we continue watching for new

23:35

updates . So in this case , even

23:37

if the effect size was a little bit skewed

23:39

, it's still incredibly likely to be

23:42

effective , at least compared to no

23:44

treatment . So have there been any more

23:46

recent studies than these initial ones ?

23:48

Well , there was a study in November 2023

23:51

in the Green Journal that looked at

23:53

using this medication for heavy bleeding

23:55

associated with fibroids . So now we're starting

23:57

to see the non-endometriosis stuff to

23:59

push that indication . They studied

24:02

the 150 milligram dose , which

24:04

is the low dose therapy , in a randomized

24:06

controlled trial of 82 patients , where

24:08

28 received placebo and 54

24:10

received the active ingredient . The study

24:12

was funded by the manufacturer . The authors

24:15

of the study , by the way , are also stockholders

24:17

in the company , so another case

24:19

of a type of conflict . Now

24:21

, if we spent some time looking at the methodology

24:24

of this paper and the results , like we

24:26

talked about in the last episode , we would find that

24:28

this study really doesn't pass muster . This

24:30

was actually over-enrolled , despite

24:32

that small size . Their power analysis

24:34

required only 48 patients in a two-to-one

24:37

randomization , but ended up with 82 . They

24:39

also had a significant number of patients lost to

24:41

follow-up , and this lost to follow-up group

24:43

favored the active intervention , which

24:46

sometimes suggests that , had those

24:48

patients been included , some of the effect size

24:50

would have been washed out . A study

24:52

like this should be an intent to treat

24:54

study , because these medications have

24:56

so many side effects and patients stop

24:59

using them or don't take them correctly due

25:01

to side effects and so it's intent to

25:03

treat , not is the way to look at this , not

25:05

the people who were protocol

25:07

. And despite all of this

25:09

, this company-funded study that over-enrolled

25:11

by nearly double and didn't do an intent to treat

25:14

analysis that would have accounted for

25:16

differences in those lost . To follow-up , the p-value

25:18

for the primary endpoint was still

25:20

only 0.035 . Now

25:23

the primary endpoint was a reduction in menstrual

25:25

blood volume to less than 80 mLs

25:27

in the last month of use , with

25:30

at least a 50% reduction in menstrual blood

25:32

volume from baseline to the final

25:34

month .

25:34

Okay , so it could be that ilegolix

25:37

is effective for patients with heavy menstrual

25:39

bleeding due to fibroids , but that conclusion

25:41

shouldn't be drawn at

25:44

least not definitively from this study .

25:46

Yeah , I think that's fair and this study would

25:48

be a great one for Journal Club , by the

25:50

way , to think about all the stuff we talked

25:53

about in the last episode whether the outcome

25:55

is valid and meaningful to patients , the

25:57

effect of choices about inclusion and

25:59

exclusion criteria , the effect of

26:01

the statistical methodologies used and

26:04

the choice to ignore those who were

26:06

lost to follow-up . They also use

26:08

some unusual statistical techniques to even determine

26:10

their p-value , and so those are

26:12

other choices that the authors made , who

26:15

were stockholders in the company and financially incentivized

26:17

to find a p-value under.05 , and

26:20

they did so . A lot of thought went into this

26:22

study design again to find

26:24

a positive effect , and your job in Journal

26:26

Club is to try to deconstruct that and understand

26:28

where they might have made different choices , but

26:31

they ended up with really a marginal p-value . There

26:33

have been those studies prior to this , so remember

26:35

. The other thing is what's already known about the topic

26:37

, and they've shown that the medication does

26:40

likely reduce bleeding associated with fibroids

26:42

. The question is whether this current

26:44

study is valid and is the finding clinically significant

26:47

?

26:47

Okay , and so far treating

26:49

bleeding from fibroids is still

26:51

an off-label indication for elagolic

26:54

. So on some level , obviously

26:56

, it makes sense that patients would have less blood

26:58

loss with a GnRH antagonist

27:01

just based on the mechanism Thanks , similar

27:04

ultimately to Luparolide , which

27:06

is the GNRH agonist

27:08

that then flips into an antagonist

27:10

action and that's already a well-established

27:12

treatment for endometriosis and

27:15

for fibroids . So we'll

27:17

allow that . There's got

27:19

to be some benefit to it , very

27:21

likely . We already have the placebo-controlled

27:23

randomized trials , although industry-funded

27:26

, that show the less pain

27:28

and dysperonia . So then we're leading up

27:30

to how it's compared to standard treatment

27:32

. Yeah , all right . So then really

27:35

the next step is should we adopt this into practice

27:37

? So what did we just say with the Metaclopramide

27:40

example ? Well , right .

27:42

So remember , we're illustrating here a sort of three-step

27:44

process . So the first step was to make sure that

27:47

at least a couple of placebo-controlled trials showed benefit

27:49

and safety . There are significant side

27:51

effects , including all the menopausal

27:54

symptoms you'd expect , similar to Luparolide

27:56

. That's why they have done the adbac therapy

27:58

in some cases and in fact the

28:00

high-dose medication is still limited to just

28:02

six months of use and the low-dose

28:04

medication to just two years of use because

28:06

of concerns for osteoporosis

28:09

. So that's a different discussion and

28:11

those are things that we learn from the placebo-controlled

28:13

trials . Are the side effects , but

28:15

the timing of the medication is limited due to

28:17

the side effects . So we have to work that into

28:19

our calculus . But remember , the next

28:21

step is deciding whether something should

28:23

be adopted into practice and the

28:26

next step is to do a comparative trial . So

28:28

some standard care options to compare

28:30

elagolics against might

28:32

be , say , 5 milligrams of north angiocetate

28:35

or other equivalent progestinone

28:37

medications , or continuous

28:39

suppressive low-dose birth control pills

28:41

or even Luparolide or

28:43

something like that and similar

28:45

. We could use similar

28:47

comparators to treat dysmenorrhea or

28:50

abnormal bleeding associated with fibroids , and

28:52

most of those medications that I just

28:54

mentioned are less than 20 bucks a month

28:56

and don't have a time

28:59

limitation for how long they can be used

29:01

due to side effects , and most of them don't

29:03

produce menopausal symptoms , luparolide

29:06

, of course , being an exception , but even

29:08

that is still , at this point , cheaper

29:10

than elagolics .

29:11

Yeah . So then the correct question

29:13

is does elagolics treat those things

29:15

better than any of those cheaper

29:18

and perhaps less morbid

29:20

interventions that we already have available

29:22

and without a comparator trial we

29:25

can't know . And it seems like

29:27

if it had a big benefit

29:29

to standard treatment , the company would

29:31

have proudly performed a comparator

29:33

trial against standard therapy to show

29:35

how superior it is .

29:37

Yeah , and for all we know , they could

29:40

still be in the works . These studies could be ongoing

29:42

now that they've established efficacy against

29:44

placebo , because that's what the FDA requires , although

29:47

, frankly , it's been around long enough at this

29:49

point that you would have expected to see a trial

29:51

like that come out , if the company were doing

29:53

one . So I'm not too optimistic about

29:55

elagolics , because Lupron , though

29:58

, already failed to demonstrate superiority

30:00

against birth control pills , and

30:02

elagolics acts basically in the

30:05

same way that Lupron does . The benefit

30:07

of this new agent over Lupron is that it's oral

30:09

and not an injection , but many of the same

30:11

limitations occur , and depolupron

30:13

was definitely better than placebo

30:15

at treating fibroids and endometriosis and

30:18

abnormal bleeding and pain . But

30:20

I'll put a link to a double-blinded control

30:22

trial , a comparator control trial from 2011,

30:25

. That showed that , lo and behold , deprolupron

30:28

was no better than continuous

30:30

oral contraceptives at treating

30:32

endometriosis related to pelvic pain . And

30:34

, of course , that paper came out many , many

30:36

years after Lupron had been heavily marketed

30:38

to gynecologists . It's very expensive

30:41

medication for that and it was no better than

30:43

birth control pills .

30:44

Yeah , that's really interesting because

30:46

you think of Lupron . If you're going to

30:48

basically cause menopause in someone , that's a

30:50

really aggressive way to minimize

30:52

the hormones that are acting on their endometriosis

30:55

. But the price point of this

30:57

new intervention plays off the idea

30:59

that it would save patients surgery

31:02

or maybe save them even

31:04

the office visit of getting the

31:06

Lupron injection . But that gets

31:08

into another thing we talked about in the last episode

31:10

of making sure that what you're claiming is supported

31:13

by the data , and none of these studies

31:15

so far that we've discussed on elgolix

31:17

here have shown that it's any better

31:19

than our normal therapies , especially

31:21

at preventing surgery . So it

31:24

would take a comparator trial to show that

31:26

, and it would also take

31:28

a comparator trial looking at something more than

31:30

just subjective pain scores and

31:32

subjective blood loss . So we

31:35

have to think about more than just

31:37

the placebo-controlled trial outcomes

31:39

when we're considering practical

31:41

use and especially a cost-benefit analysis

31:43

.

31:44

Yeah . So I , for example , didn't

31:46

use depilupron years ago when

31:49

it was being marketed for this , and I've

31:51

not used this new medication because

31:53

it didn't pass muster of what we're

31:55

talking about Now . The next step

31:57

of this medication will

31:59

be combining it with ad-bac therapy

32:01

so that it can be used longer than two years

32:04

. We're already seeing that , and that may somewhat

32:06

counteract the benefit , but also would

32:08

allow the medication to be taken continuously

32:10

. So now you have , let's say , a 32-year-old

32:13

woman who's suffering from endometriosis

32:15

and the company would be happy for her

32:17

to take it for the next 20 years until

32:20

the patent expires , at a cost of about

32:22

$300,000 over that time

32:24

, compared to a

32:26

cost of about $3,000 for

32:28

continuous birth control pills over that time

32:31

or , frankly , even surgery .

32:32

Yeah , so you're talking about elgolix combined

32:35

together with estrogen and norethin drone

32:37

as like a combination ? Right . The

32:40

medication similar to this is

32:42

relu-relugolix , and

32:44

there are a lot of European trials looking

32:47

at this medication for the same indications

32:49

and so far nothing groundbreaking

32:52

has come out of that to suggest

32:54

that these truly would be superior

32:56

to birth control pills , and especially

32:59

not to the same degree of how much more

33:01

they cost . And really

33:03

, if you think about it , what they're adding back basically

33:06

is a birth control pill . Yeah . It's oral

33:09

progestin and estrogen , and

33:11

at the doses that they're adding them back

33:13

, it wouldn't even be enough to prevent

33:15

pregnancy . So then the patients are on

33:18

these birth control hormones , but

33:20

then they still have to take something else for birth control

33:22

.

33:23

Yeah .

33:23

So it's silly , especially

33:25

if you have a patient who doesn't want to be on

33:27

hormones or something . Yeah

33:30

, it doesn't make any sense to me , honestly

33:32

.

33:32

Yeah Well , and this is

33:34

why things like this are heavily marketed , because

33:36

at their surface they don't

33:38

make sense . So this is a great example

33:40

and a great study again for Journal Club

33:43

that gets into whether or not we should

33:45

be using a new intervention . New

33:47

sometimes equals better , but it's rare

33:49

. Honestly , we need to know that

33:52

the new is better than the old , and

33:54

the only way to do that is with a comparator trial

33:56

that shows either improved safety or

33:59

improved efficacy or both , hopefully or

34:01

something that justifies the cost

34:03

of the new medication . In this case , it's

34:06

likely that these medications are no better than

34:08

continuous OCPs or iGestin

34:11

, which is the 5 milligram north end on acetate

34:13

that treating these symptoms that patients have

34:15

, and , by the way , we know

34:17

that it has a worse safety profile than

34:19

those medications nearly 100 times

34:21

the cost .

34:22

Yeah , so the need for replicated data

34:25

compared to trials is maybe the most

34:27

important takeaway from this

34:29

episode . In the last one , there's a

34:32

lot of detail in analyzing a journal

34:34

article that people do need to

34:36

brush up on to be able to do it correctly , and

34:39

there's a lot of great , very

34:41

digestible resources out there . Obviously

34:43

, your book , clinical Reasoning , is top notch

34:45

for that . There are also some YouTube

34:48

videos and for people who are more auditory

34:50

or visual or like lazy learners

34:53

, that at least can help with

34:55

like single concepts Maybe not as

34:57

comprehensively as how you laid it out , but

34:59

anyone can at least ask

35:01

these basic questions that we've just

35:03

reviewed without doing any

35:05

further studying on their

35:07

own and see if the data answers

35:10

them . But even if you believe that

35:12

this company funded trial looking at elagolics

35:14

for fibroids that was published in

35:16

the Green Journal is a good study

35:18

that found a clear benefit because

35:21

you didn't know enough to deep

35:23

dive into the authors tricks they might have

35:25

used , even if you didn't know

35:27

that , you still should

35:29

already know not to use this medication

35:32

if you're asking these big

35:34

questions and realize there's no evidence that

35:36

it's better or safer or cheaper

35:38

than what we're already doing .

35:40

Right . Yeah , the rest is just marketing , and

35:42

that's where most of the mistakes are made in clinical practice

35:45

with adoption of new interventions , like

35:47

a lot of the things , of course , we talk about . We

35:49

mentioned some of the trickery used in some of the

35:51

articles about the fetal pillow in the

35:53

as an example in the last episode . There's

35:56

an opportunity there as well for a comparator

35:58

trial . A good trial would be to take the

36:00

fetal pillow and compare it not

36:02

to placebo , meaning noninflation

36:05

, but to using other acceptable techniques

36:07

like reverse reach extraction or the pet warden

36:09

maneuver or a vaginal hand , and , if possible

36:12

, to randomize patients to which

36:14

intervention they receive . It would also look

36:16

for clinically meaningful outcomes that

36:19

matter to our patients , like how much blood

36:21

loss was there or it

36:23

was a baby admitted to the NICU or other neonatal

36:25

outcomes , not simply how many seconds it

36:27

took to deliver the baby .

36:29

Right , okay , well , I think we

36:31

have time for one more article , the

36:33

one about the doulas , because we also want to get to a listener

36:35

question . So we picked this

36:37

virtual doula article from

36:39

the February 2024

36:42

Green Journal called Association

36:44

Between Doula Use on a Digital Health Platform

36:47

and Birth Outcomes . So they

36:49

concluded that virtual doula

36:51

support on a digital health platform is

36:53

associated with lower odds of caesarean

36:55

birth and an improved birth experience

36:58

, and they also added some information

37:00

about outcomes , specifically in black women

37:03

.

37:03

Right , and they may be on to something with the

37:05

patient experience part for sure . But unfortunately

37:08

again , the study design here is incapable

37:10

of providing a conclusion on caesarean

37:12

rates .

37:13

Okay , I figured you'd say that , so

37:15

walk us quickly through that .

37:17

Well , first of all , the study was reformed again

37:20

by the company and employees or

37:22

stockholders of the company , so there is

37:24

a financial incentive to construct a study

37:26

in some way that supports increased

37:28

advocacy for payments for this service

37:30

from insurers . Beyond that , though , the

37:32

main issue is that this is a retrospective

37:35

study of women who were given access

37:37

to the product , which is called MAVEN , as

37:39

part of their insurance plan through their employer

37:42

or their spouse's employer , so they identified

37:44

almost 9,000 pregnant patients who

37:46

had access to the app and essentially

37:48

compared the pregnancy outcomes of people

37:50

who used the app to those who didn't use

37:52

the app , and the vast majority of patients didn't

37:55

use it at all , or at least didn't attend any

37:57

of the appointments with a doula , but

37:59

some patients used it quite a bit . So , essentially

38:01

, what the study is capable of demonstrating

38:04

is that people who chose to

38:06

have regular appointments with a doula had

38:08

a lower rate of caesarean delivery compared

38:10

to those who did not choose to have regular appointments

38:13

with a doula .

38:14

Yeah , so there's always going to be a limitation

38:16

in retrospective type data and

38:19

in fact that conclusion

38:21

seems almost intuitive

38:23

. Acog already recognizes the

38:25

potential value of a doula or other

38:27

similar dedicated emotional

38:29

support people in terms of labor outcomes

38:32

, and doulas can

38:34

certainly be helpful with

38:36

any kind of birth if

38:38

people want one , including caesarean

38:40

, including postpartum recovery . There's

38:43

also doulas out there for abortion . There's

38:45

end of life doulas , so have

38:47

emotional support for everything I say .

38:50

Can I have a doula for Mondays ?

38:52

Yeah , I want one too . We could all use a little more

38:54

support for regular life struggles . Back

38:58

to the labor . If you think about the

39:00

kind of person who's going to be proactive

39:02

in seeking a doula for any reason

39:04

, they're likely doing other things

39:06

as well to promote having a good outcome

39:09

for themselves . So in the context

39:11

of labor , a good outcome would include avoiding

39:13

an unnecessary caesarean , and

39:16

so that person who has a doula

39:18

for pregnancy and labor may

39:20

also be seeking out a practice with

39:22

a known lower caesarean delivery

39:24

rate . They may resist elective inductions

39:26

, at least with an unfavorable cervix

39:28

, or other interventions like

39:30

admission for early labor

39:33

, because both of those are also known

39:35

to be associated with higher caesarean rates

39:37

.

39:38

Yeah . So the problem is , was it the doula or

39:40

was it something else ? The patient who was

39:42

predisposed to seeking out a doula was

39:44

also doing , or combination of the factors

39:46

that led to a lower caesarean

39:49

rate in the study .

39:50

Yeah , and obviously this retrospective

39:52

study cannot separate out confounders

39:54

like that . It's looking at self-selected

39:56

, non-randomized groups and , anecdotally

39:59

, I would argue that providers also

40:02

manage labor a bit differently when

40:04

there's a doula . So with this

40:07

app , I don't know if they turn

40:09

on their app and they're talking to the doula in

40:11

the room , the labor room or what

40:13

, or if they walked in with a really detailed

40:15

birth plan , but a doctor

40:17

that's taking care of a patient like that might

40:19

be more likely to give the patients extra

40:22

time , even in the setting of protracted

40:24

labor or prolonged pushing , for example

40:26

.

40:27

Right . Well , the point , though , is , if

40:29

you claim that doulas cause

40:31

a lower rate of caesarean delivery based

40:33

upon this study or studies similar

40:36

to this , well , that would be overstepping

40:38

the evidence and the actual data

40:40

. All this really says is that

40:42

people who are interested in using doulas

40:44

are the sorts of folks who have lower

40:46

rates of caesarean delivery , and that's

40:48

still an interesting outcome . But a randomized

40:51

, controlled trial , where people were assigned

40:53

to use either a doula , or , say

40:56

, an in-person doula or a virtual

40:58

doula service like this , versus

41:00

some other intervention , like , maybe , watching

41:02

a series of educational YouTube videos

41:04

that provide information about labor

41:06

or even just standard care , with

41:08

nothing , that would be the only appropriate

41:11

way to conclude whether the intervention

41:14

has a direct effect on lowering rates

41:16

of caesarean .

41:17

Yeah , and I think even the part about patient

41:19

satisfaction in this study was a circular

41:21

argument . So they did some pretty

41:23

complex appearing analyses to

41:25

say that the more a patient used

41:28

this app , the more satisfied they were with it . So

41:30

, of course , like I use

41:32

a bunch of apps on my phone , I don't use this

41:34

doula app , of course , but I

41:36

use the ones I like more and

41:39

then I don't use the ones that I don't like

41:41

. So I do need to try to cut

41:43

back on my phone scrolling time anyway

41:45

, but that's another story . But I'm more satisfied

41:48

with the apps that I use a lot . That's the point of that

41:50

, so don't need to do a statistical

41:52

.

41:52

Yeah , I'm also a bit of a texting

41:55

junkie , but yes , it's heavily biased

41:57

. I'd say this paper is low quality

41:59

and shouldn't change anyone's clinical practice

42:02

, nor should it be used to advocate

42:04

for payments for this particular service

42:06

. That doesn't even mean that the service is bad

42:08

, like folks . Don't take this as a criticism

42:10

of Maven or doulas or

42:13

that at all . It just means

42:15

that this paper doesn't demonstrate

42:17

that that service will improve outcomes

42:19

for people who aren't already interested

42:22

in that . So this potentially gets into

42:24

medical justice . If we're not doing

42:26

our due diligence to make sure that an intervention

42:28

benefits more than just an

42:31

exclusive , self-selected population who

42:33

may already be at lower risk at baseline

42:35

, we might be violating justice by advocating

42:37

for it . So design the study to show

42:39

what you want to show and don't make conclusions

42:42

that aren't demonstrated by the data .

42:44

Yeah , we always want to be pushing for

42:46

medical resources to be used

42:48

for something that either benefits

42:50

a broad general population or

42:53

at least benefits people that have higher

42:55

risk of really significant bad outcomes

42:58

. And here they did talk

43:00

about the value of this doula service specifically

43:02

for black people , and we know that they

43:05

have higher rates of birth

43:07

complications . We've talked about

43:09

that before .

43:10

Higher rates of cesareans .

43:11

Yeah , and it's still possible

43:13

that it does help and that

43:15

it does help black people . But

43:17

it could also be the case that an alternative

43:19

intervention could be just as effective

43:22

and much lower cost . Like they

43:24

didn't explore a series of maybe 15

43:26

or 20 minute long educational videos

43:29

, and that would be

43:31

a lot cheaper than an app . I also

43:33

think that providers and health systems

43:35

need to continue to push to

43:37

institutionalize their best practices that

43:39

include safely limiting interventions

43:42

in labor , like ACOG already lays

43:44

out in their committee opinion , because

43:47

then it wouldn't be putting the onus on the

43:49

patients to be have to be the proactive

43:51

ones to push for things . It really should

43:53

be how we treat every patient .

43:55

Yeah Well , the company has a

43:57

product that they want to sell and it's up to the

43:59

company that wants the money to do

44:01

a study , appropriate study , and this

44:04

one just isn't it . But it is very

44:06

typical of the type of literature

44:08

we see published almost every week in our journals

44:11

and it's usually glossed over with very

44:13

little critical review . But I hope what we've

44:15

shown today is that it doesn't take much

44:17

critical analysis . You don't have to be a statistical

44:19

expert to quickly just think about

44:22

the design and think about what the intention

44:24

is and separate the good from the bad . You

44:26

don't have to be an expert , you just have to ask the

44:28

right questions .

44:29

All right . Well , let's move on to the listener

44:31

questions segment .

44:32

Speaking of questions .

44:35

Yes , well , we have a couple . These ones

44:37

are pretty exciting , so

44:39

you go first .

44:41

Okay . Well , I have a question from a listener , dear

44:44

Obi . I don't know how we're

44:46

going to say . Like Abby , Dear Obi . I

44:48

went to the doctor for my annual visit and they

44:50

charged me 200 bucks for my Lexapro

44:53

refill because it was out

44:55

of scope for the annual visit . Signed

44:57

, depressed , undressed and

44:59

worth $200 less .

45:01

Okay , I assume you made up that tagline

45:04

. So you're assuming that she got an

45:06

unnecessary pelvic exam ?

45:08

She did . Well , this person

45:10

is in her 20s and has commercial insurance

45:13

with a high deductible but of course

45:15

gets an annual preventative exam paid

45:17

for without copay . So she goes to

45:19

the doctor for what

45:21

she thinks is a covered checkup

45:23

without having to pay against her deductible . She

45:26

gets a breast and pelvic exam that she doesn't

45:28

need and then she asks for a

45:30

refill of her Lexapro that her primary

45:32

care provider had started for her previously

45:34

, and later she finds out

45:37

that this was billed as a separate in and

45:39

visit and is not covered

45:41

without copay . So she ends up paying

45:43

the whole bill for that in M because

45:45

she hasn't met her deductible for the year .

45:47

Yeah . So her provider might consider

45:50

ongoing depression treatment outside

45:52

of the scope of a general well exam . So

45:54

technically you could argue that it is

45:57

, and so then they might code it as such

45:59

without appreciating how

46:01

both expensive and unexpected

46:04

that little click of a button they did

46:06

became for their patient . And

46:08

this is something with very little transparency

46:10

on both sides . I'd say that if there

46:12

wasn't a very attentive discussion

46:15

or assessment of depression and

46:17

it literally was just fulfilling the request

46:19

for the med refill , it's not really

46:21

correct or fair to bill for it . But

46:23

there's not a lot of oversight into

46:25

the correct coding in a lot of clinics

46:28

. So it ends up really being

46:30

on the providers to know

46:32

what constitutes over coding versus

46:34

under coding . And unfortunately

46:36

we just often have to teach ourselves this

46:38

on our own time and maybe pay for the coding

46:40

guides or seminars that

46:43

we would do outside of normal patient care hours

46:45

. We know that we can get

46:47

fined and heavily penalized

46:49

for over coding , so we don't want

46:51

to do that . But if we under code we

46:53

also will rob our own clinics of getting

46:56

appropriate resources that will keep

46:58

taking care of all of our patients . So

47:00

for the doctor , coding it's probably

47:02

not even a conscious matter of how

47:05

much is going to end up in their own pocket . It's

47:07

probably negligible , but it's

47:10

whether or not . Just as a routine

47:12

, are we doing right by both this individual

47:14

patient and also by the whole clinic and the rest of

47:16

our patients whenever we decide how

47:18

we code for things ?

47:19

Well , yeah , the hospital leadership gets a cut

47:22

of this too , and I don't know if this is a privately

47:24

owned practice or a corporately owned or whatever

47:26

, but an unethical administrator

47:28

might pressure clinicians to over code because

47:31

of that revenue stream . It's a tricky balance

47:33

because hospitals and large

47:35

systems have to either pay extra money

47:37

for a professional coder to do this correctly

47:39

, which is often lower yield in clinics

47:42

as opposed to inpatient settings , or

47:44

save the money on the administrative staffing

47:46

and pass the work down to the provider and

47:48

just hope they're doing it right most of the time with

47:50

the occasional random audits . And

47:53

here's a fun fact I was recently told

47:55

by my chart auditor that I

47:58

should have billed for this exact same

48:00

thing . A patient came in for her annual preventive

48:02

health exam and I addressed her mood , prescribed

48:05

medication and did not charge her

48:07

a separate visit for that , and

48:09

the auditor told me I messed up .

48:11

Wow nice . How did you respond to that auditor

48:14

?

48:14

Well , I told her that the main purpose of the

48:16

annual preventative visit was

48:19

to address things like mood disorders and

48:21

I pointed her to the US Preventive Task Force

48:23

Guidelines and the Women's Preventative Service

48:25

Initiative Guidelines regarding what

48:27

should be done at a women's preventative

48:29

visit . And sure enough , these

48:31

are the things a patient in her age group

48:34

should be getting each year at that preventative

48:36

health visit Alcohol use screening

48:38

and counseling , anxiety screening

48:40

, blood pressure screening , contraception and contraceptive

48:42

care , depression screening , diabetes

48:45

screening if she has risk factors , folic

48:47

acid supplementation , healthy diet

48:49

and activity counseling , interpersonal domestic

48:52

violence screening , lipid screening if

48:54

she has risk factors , obesity screening

48:56

and counseling , substance use screening and

48:58

assessment , tobacco screening and counseling

49:00

, urinary and continent screening and

49:02

then STI prevention and counseling and

49:04

screening is appropriate , and immunization

49:07

screening and things like that . She should also be

49:09

screened for the need for BRCA

49:11

or other genetic testing related to her family

49:13

history and she should get a pap smear every

49:15

three years as she's under age 30 , as this patient

49:17

was .

49:18

Yeah , so obviously the well exam

49:20

is not just pap . Breast exam

49:22

bill for everything else , that's not that .

49:25

Which is what everybody thinks it is , including the coders .

49:27

Yeah . So then it becomes a philosophical

49:29

question of whether or not the screening

49:31

is also treated . Is that still

49:34

within your scope ? In other words

49:36

, maybe we screen for anxiety or depression

49:38

and when we identify it , do

49:40

we separately charge for treating

49:42

it ?

49:42

Yeah , well , you could do that . It's technically

49:45

legal , but the auditor came back and agreed with

49:47

me that it was also justifiable to not

49:49

make a separate charge and took away her

49:51

failure for me on that chart

49:53

, but maybe you maybe it depends . Maybe

49:56

you refer the patient for counseling or you refer

49:58

them to a mental health care provider . Once you identify

50:00

the issue , maybe you started medication and have

50:02

them follow up with you . The choice to charge

50:05

or not is perhaps based upon the complexity

50:07

of those choices . If you spent

50:09

45 minutes with a patient in crisis

50:12

dealing with depression who

50:14

just happened to be scheduled for her annual preventative

50:16

, well , that's a bit more complex and urgent

50:19

and you really should probably

50:21

charge for your time and services . But

50:23

the goal of the preventative visit is screening

50:25

, prevention and perhaps referring

50:27

for appropriate and focused follow up of any

50:30

new issues identified , all without having

50:32

an extra cost associated with it , so

50:34

that people come and get these services . Think

50:36

about the birth control component . We do

50:39

contraception and contraceptive care , but

50:41

when we screen the patient to see if she needs

50:43

birth control say she needs a refill

50:45

or a prescription for birth control pills we

50:47

don't then charge her a separate visit

50:50

to prescribe the birth control . So

50:52

I think this is a question of sort of ethics

50:54

and is an illegally or technically

50:57

gray area , but that's where we

50:59

use our ethics to guide us .

51:01

Did this listener indicate how much time in

51:03

the visit was spent discussing this lexapod

51:06

refill ?

51:07

Yeah , it sounded like it was less than a minute or two

51:09

. Just a very casual conversation about

51:11

how she was doing , and sure I'll send you a refill

51:13

in .

51:13

Yeah , so okay . So billing for that just

51:16

seems wrong , like what's the

51:18

chance she's going to go back to that provider every

51:20

year anymore ? That

51:22

wasn't her main purpose for coming in to

51:24

lexapro refill . It was for the annual

51:26

.

51:27

Yeah , so ethics or everything .

51:29

All right . Well , I also got an interesting

51:31

question I wanted to bring up on

51:33

here . So , drob , should

51:36

a mid 30s woman who doesn't

51:38

have a partner but wants children in the future

51:40

consider O-site cryopreservation

51:43

? What about embryos versus just

51:45

eggs ? Or is this all just

51:47

a marketing scam to get anxious women

51:49

to pay thousands for storage fees ? Asking

51:52

for a friend who is always an auntie

51:54

, not yet a mommy .

51:56

Okay , interesting . So I guess this

51:58

one should be to deer always an auntie . So

52:01

what's your answer ? I feel like this could

52:03

be one of those things where it's marketed

52:05

obviously to anxious patients , but

52:07

is also a great thing for many

52:09

patients who are in that situation

52:12

. Things are rarely good or bad

52:14

, but the truth is somewhere in the middle . So

52:16

, people , this can be fantastic for

52:18

some people and maybe unnecessary

52:21

for others .

52:22

Yeah , this is so individual and

52:24

it's really down to family building and

52:26

there's so many options for that . So I'm

52:28

just going to hit this . I'm going to review

52:30

the alternatives to family building

52:33

besides the cryopreservation , see where

52:35

the cryopreservation fits in and

52:37

then see what the professional societies

52:40

say . So these are just the

52:42

options that I can think of , in really

52:44

no particular order and probably not all

52:46

encompassing . So one thing you

52:49

can do is just do nothing , wait and

52:51

see what happens If you get a partner

52:53

one day or whatever . Try naturally , but

52:55

then be okay with possibly never having

52:57

a child . So that's one option . Another

53:00

option plan to adopt , which

53:02

, besides biologically for your

53:04

own body , is a very complicated

53:06

process , very happy . Another

53:08

option is , if you get

53:10

past the age where you have any viable

53:13

O-sites yourself , you could plan on using

53:15

donor eggs and then

53:17

either your partner's sperm or sperm

53:19

from a bank , usually a healthy woman

53:22

that has gone through this process for

53:24

money , not as part of her own

53:26

family building process , where then there was just extra

53:28

. Another option is you could plan on using

53:31

donor embryos , and these

53:33

are often like the side product

53:35

of couples who were going through

53:37

IVF and then got more embryos than they ultimately

53:40

were able to do transfers with , and

53:42

then they have chosen to put these up for

53:44

putting them up for adoption is

53:46

one way to say it rather than letting them

53:48

be discarded . And that doesn't mean these

53:51

are free . The donor family doesn't get compensated

53:53

, but the clinic and lab fees are still

53:55

very high for these sometimes . Another

53:57

option is this option that our listener

54:00

asked about is go through the egg

54:02

retrieval process now of your own eggs

54:04

while you're in your 30s or just sometime

54:06

before you have significant age-related

54:09

decline and you pay for

54:11

the storage and you hope that eventually

54:13

one day you'll get into a situation where you

54:15

could get your eggs fertilized and proceed

54:18

with pregnancy that way . And

54:20

another sub-option here to consider

54:22

is because eggs

54:25

alone don't have quite as good of a rate

54:27

as surviving the thawing process compared

54:30

to fertilized eggs or aka embryos

54:32

. You could even go

54:34

through the egg retrieval now and get some of the eggs

54:36

fertilized , and this would depend

54:38

on your situation as to whether you're going with anonymous

54:41

sperm through a donor or if you

54:43

already have a partner or someone

54:45

in your life that would be willing to be the biological

54:48

, genetic father of your kids and

54:50

be involved in this , and then , I think , the

54:53

most biologically complicated option

54:55

, in my view , would be , at an advanced

54:57

age , going through IVF later

55:00

on , once you've found your partner or

55:02

picked a planned sperm donor

55:05

, simply because the chance of success may

55:07

be much lower depending on your age at the time .

55:10

I think you've made more questions , but we'll

55:13

compare those options for us then .

55:15

Yeah . So

55:17

I'm assuming she wants a child , so

55:19

she doesn't want the option of being okay

55:21

with never having a child and not doing anything at all

55:23

. The per cycle chance

55:26

of conception over

55:28

age 40 just naturally

55:30

trying to conceive is often quoted as less than 5%

55:32

, whereas at peak fertility

55:35

in the mid-20s it's 25%

55:38

chance with just one intercourse

55:40

. By age 50 , it's still as high

55:43

as 1% chance if you're not on birth

55:45

control and don't have other reasons for infertility

55:47

. So those are just the chances

55:49

to consider . So very low chance

55:52

of spontaneous conception if you get over 40

55:54

is the bottom line up front . I'm

55:56

going to go ahead and skip any further commentary

55:58

on adoption . I don't really have experience

56:01

with this , but I know that it can be very

56:03

extensive and emotionally

56:05

draining and costly . So

56:08

if someone is interested in it

56:10

, not as a plan B for

56:12

fertility but just in general , then

56:14

maybe they can send us their experiences

56:17

and we can talk about it . But it's probably

56:19

not the best thing to do

56:21

this as a plan B because it might

56:23

actually be harder than the other

56:26

options we're going to discuss . So

56:28

then we're getting between getting

56:30

egg retrieval now versus

56:32

in the future using donor eggs or

56:35

donor embryos or IVF . So donor

56:37

eggs . If you're older and you're using

56:39

donor eggs that were obtained from a healthy

56:41

young donor , there's a 51%

56:44

chance of a

56:46

fresh transfer resulting in a live birth , regardless

56:49

of how old you the patient

56:51

are at the time of the pregnancy

56:54

. There are still higher perinatal

56:56

risks using a donor egg versus using

56:58

your own egg , and that's likely multifactorial

57:00

, but that would include preterm birth , low birth

57:02

weights , then still birth Deterior

57:04

embryos . If you're okay using

57:07

being pregnant with someone that

57:09

is not genetically related

57:11

to you or to your partner , it

57:14

is cheaper than IVF because you're skipping

57:16

the whole egg retrieval and stimulation process

57:18

. For yourself , it is about one third

57:20

of the price and there is about 40%

57:23

chance of having a live birth per

57:25

attempt or per cycle . So

57:28

it's not per se adoption

57:30

, because as soon as this embryo

57:32

has implanted into your uterus , it's

57:35

fully legally yours . Once

57:37

you give birth , it's yours . The

57:39

genetic , the biological

57:41

origins of the egg and sperm

57:44

have no legal claim on this

57:46

person . So that might be one

57:48

pro compared to adoption

57:50

. If you're okay with having a child

57:52

that's not genetically yours , the

57:55

genetic relation thing is just something everyone

57:57

has to consider for themselves . If that

57:59

is important to you , then you're looking

58:01

at either egg retrieval now or

58:04

going through IVF later in life , and

58:06

really it is . I'll

58:09

just sum it up getting an egg retrieval

58:11

now to maybe go through IVF

58:13

later is better than just

58:15

waiting to go through IVF later

58:17

. It's more cost effective , it's

58:20

higher rates of success and I

58:22

can break that down a little bit more . But there's

58:25

been some cost breakdown studies

58:27

on this in the fertility sterility journal we

58:29

can link to . And as

58:31

far as , what does ASRM and ACOG

58:33

say about this ? Acog doesn't directly address

58:35

it . They just say expedited fertility

58:38

evaluation immediately at 40

58:40

years old . So it's essentially

58:42

they're in short form . Differing to ASRM

58:45

is how I read that between the lines , because

58:47

people at 40 years old that haven't

58:49

spontaneously conceived , they're going to get escalated

58:51

care pretty quickly . So ASRM

58:53

has a 2021 guideline called Evidence-Based

58:56

Outcomes After Ocite Crier Preservation

58:58

for Donor Ocite IVF

59:00

and for Planned Ocite

59:02

Crier Preservation . So it's

59:05

been since at least 2013, . They've recognized

59:07

it as standard care , so not experimental

59:10

, not just some gimmick to try to get

59:12

more money , at least for indications

59:14

like fertility preservation for

59:17

people that are undergoing cancer treatment that

59:19

haven't you know , they haven't started

59:21

or they haven't at least completed their family

59:23

building yet . And in this 2021

59:26

guideline . Finally , they also recognize

59:28

just delayed childbearing and also

59:30

gender transition as other indications

59:33

to go through quote unquote

59:35

freezing one's eggs . So they

59:37

say that the evidence on the outcomes is still

59:39

limited but from what has been

59:41

observed so far , the live birth rates

59:44

are roughly equivalent between this and

59:46

someone that's going through conventional

59:48

IVF at that same age . So

59:51

that includes rates of embryo transfer per

59:53

cycle , rates of ongoing pregnancy

59:55

per embryo . They really they said

59:57

there's small studies so they gave caveats

59:59

on each one . So when it gets to age

1:00:02

like okay , I agree that this is better

1:00:04

than waiting till I'm 42 to start IVF

1:00:06

. What would be the latest age

1:00:09

to start this and how long do I have

1:00:11

to think about this ? They said the clearest

1:00:13

threshold for difference in outcomes

1:00:15

is getting the egg retrieval done before

1:00:17

age 38 . So before

1:00:20

versus after , the clinical pregnancy

1:00:22

rates were 60% versus 44%

1:00:25

respectively . So basically

1:00:28

, my answer to this listener is yes

1:00:30

. If you're thinking that you're

1:00:33

not going to have started your family otherwise

1:00:35

by age 38 , then

1:00:37

and you really want genetic children

1:00:40

, I would say by the before

1:00:42

you get to age 38 , really consider

1:00:45

freezing your eggs . Overall the costs

1:00:47

they're high . They're comparable to the respective

1:00:49

IVF costs plus yearly

1:00:51

storage of the eggs or embryos , which that

1:00:54

ends up being about another $500

1:00:56

, maybe up to $1,000 per year , for

1:00:59

not per embryo or not per egg , but

1:01:01

for your whole amount

1:01:03

, even if you had 50 eggs or something

1:01:05

. Of course that could change by clinic

1:01:07

and over time , but that's going to be an

1:01:10

almost negligible cost compared

1:01:12

to everything else you did to go through the

1:01:14

egg retrieval . It's still going to be

1:01:16

cheaper than trying to start IVF after

1:01:18

38 . So there that's my answer

1:01:20

.

1:01:21

Well , and there are cheaper options . I've

1:01:23

had a lot of patients use CNY fertility

1:01:25

, which has offices now around the country

1:01:27

, but they're primarily based in New York . But they

1:01:30

are significantly cheaper . Usually I have

1:01:32

to even a third of the price of other fertility

1:01:34

operations . So I did look on their website

1:01:36

. Their egg freezing packages are

1:01:38

$4,800 . And

1:01:40

they say that compares to a national average of

1:01:42

nearly 15,000 . And I think

1:01:44

that they're yeah , and I've had several

1:01:46

pregnancies . This is the maybe the new

1:01:48

face of fertility and I think that their yearly

1:01:51

storage fee is about $600 , which

1:01:53

again is about half of the freezer fees

1:01:55

you see in a lot of places . So it

1:01:57

can be done for less money . A

1:02:00

little bit of travel in that case , and

1:02:02

you should shop around and comparison shop

1:02:04

. These protocols for a lot of these things

1:02:06

are fairly standardized around the country and

1:02:08

you can move embryos from place to place or move

1:02:11

eggs from place to place , depending on your situation

1:02:13

. So hopefully that answers your question

1:02:15

. There's a lot to unpack there . We could spend a whole hour

1:02:17

.

1:02:17

Yeah , so good luck to

1:02:19

our listener . Hopefully , whatever

1:02:22

you choose to do , it works out the way you want

1:02:24

it and hopefully that helps other listeners

1:02:26

as well . But I think we need to wrap

1:02:28

up now . We might have gone over time a bit

1:02:30

. So the thinking about OBGYN

1:02:33

website will have links to

1:02:35

the things that we discussed and , of course

1:02:37

, check out our Instagram if you haven't already

1:02:39

. Our little ninja has been posting

1:02:42

fun little tidbits here and there , and

1:02:44

we will be back in a couple of weeks with

1:02:47

something new .

1:02:52

Thanks for listening . Find us online at

1:02:54

thinkingaboutobgyncom . Be

1:02:57

sure to subscribe Work for new episodes

1:02:59

every two weeks .