You have all good points:
1. where / in what sample is the measurement made?
2. what is/are measured? the direct analyte or a validated proxy?
3. what technique is it measured by?
From half a decade back, I have technical and biz dev experience developing a saliva test using an aptasensor-based approach for quantification of malarial biomarker(s),
with an additional ability to distinguish between Plasmodium species!
But sex steroids is a different matter, and I have to do quite a bit of reading to get into the nuts and bolts of this...
The thoughts I've shared in this thread are based on my casual discussions with REIs both in private practice (Orange County, Hampton Roads), and
at university medical hospitals (UC-Irvine, UC-Davis, VCU, JHU etc.)
Current treatment methods for infertility treatments do not appear very fine tuned.
Reproductive endocrinologists and infertility specialists (REIs) often clump patients on groups loosely based on severity of symptoms and other factors such as BMI, antral follicular count etc, and consequently their fertility treatment protocols are not necessarily reflective of their hormone status - which varies even diurnally as a function of circadian rhythm, and is therefore a rather glaring omission.
This is not because REIs are not interested in continuous monitoring of hormone levels to better inform their treatment protocols.
But I understand it is only because such methods are not yet available!
Regarding your mention of stress as a reason for infertility - agreed.
However, stress is a complex environmental factor / variable. What may be a stressor for me, may be pleasant for you, and vice versa.
Though some markers of stress are common across all humans, each body's response to the same profile of stressors is likely to be different.
Perhaps more importantly, there is no magic pill for stress! :)
So I would rather stick with the basics - as noted below.
- can I measure [hormones] with good performance (sensitivity, specificity, recall, precision, FPR, FNR - however you wanna evaluate)
- in patients, can I correlate infertility symptoms with continuously monitored [hormones] -> right now, they are 24 hour spaced time series measurements, and
- finally, can I alter [hormone] via administration of pills / injections to restore fertility (partial / complete)
BTW, I am not thinking just for myself, but way beyond, for what I think is a reasonable market opportunity, i.e. can be monetized easily IF such continuous hormone quantification will work, and with social benefit - A reliable, inexpensive hormone monitoring system could result is multiple efficiencies - save so much time, money and heartbreak for so many wannabe mothers, and make it simpler for so many reproductive endocrinologists and save money for health insurance companies too!
I welcome folks to add to this, or to poke holes in my as yet amorphous scientific / clinical / efficiency rationales. Cheers!
On Tue, Apr 13, 2021 at 9:25 PM drllau <drlawrencelau@gmail.com> wrote:
3 questions come to my mind
1) biomarkers - where are they most likely to be excreted (milk?) or non-invasively detected ... this impacts the gear you use to collect, separate and detect samples.
2) reliable biomarkers - if you can't measure what you want directly, are there indirect substitutes (metabolic breakdowns) or other endocrimes with high correlation? ... the problem is that without a baseline, finding the deficiency of a hormone is harder than detecting the minute quantities
3) reliabile biomarkers fo RCA - (root cause analysis) ... infertility is due to a range of factors . I'm an academic doc so I can't give any advice but I presume you've done your lit search to find tests (or gotten copies of prior) that can eliminate many contributing inhibitors. It may all boil down to "stress" so I hope you've thought hard about the route you're taking rather than spending time/money on a post-honeymoon idyllic island for a few months where you can go at it hammer and tongs.--On Saturday, 10 April 2021 at 12:21:14 UTC+8 Tom De Medts wrote:Dakota, Frank - thanks for your replies.A video explaining how the CGM works - https://www.youtube.com/watch?v=1FecOjMsgMwIt's by Dr. John Mastrototaro, "father of CGM", describes how a continuous glucose monitor works for people with diabetesAnd this work done in Medtronics' Diabetes Division.I hear what you say about fertility being a complex issue, and that is why I do not want to go down that routeInstead I want to 1st focus on what is technically feasible before delving into whether results are biologically possible (cross-contamination from other steroid etc)Here is an example 2019 paper where the aptamer is discovered using what I think is a sequential and pooled SELEX, or something like that?https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893951/ It's close to midnight here, I'll read it later and carefully.But something caught my attention in this paper - "Binding studies demonstrated the high affinity of each selected aptamer for its respective target, and low nanomolar range dissociation constants calculated were similar to those previously reported for steroid-binding aptamers selected using traditional SELEX approaches. Finally, the selected aptamers were exploited in microtiter plate assays, achieving nanomolar limits of detection, while the specificity of these aptamers was also demonstrated. "I've got to find out at least 2 things:1. Are the concentrations of target analytes even lower that aptamers' nanomolar limits of detection sensitiity?2. CGM monitors [glucose] in interstitial space, are there even target analytes in this fluid, otherwise is continuous monitoring ruled out for a sensor that has to enter the lumen of any blood vessel?This requires a lot of reading on my part, and consultation with smart folks like you.So if you have additional ideas, keep them coming, thanks!Cheers,TomOn Fri, Apr 9, 2021 at 4:06 PM Frank <fgarc...@gmail.com> wrote:Yeah, you're not going to find something that can do continuous
monitoring of those hormones. But if the core problem is the fertility
then that's a different matter. I'm no expert but I do know this is an
area where a great many issues and factors can influence things. Some
of those fall outside of what we would assume interfere with fertility
and don't usually get considered by the typical fertility "expert".
------ Original Message ------
From: "Dakota Hamill" <dko...@gmail.com>
To: "diy...@googlegroups.com" <diy...@googlegroups.com>
Sent: 4/9/2021 2:53:56 PM
Subject: Re: [DIYbio] Continuous (blood) Analyte Monitoring
>Everything is either an ELISA or ECLIA test as far as I know, with the
>steroids also offering LC-MS/MS for higher sensitivity. I've done the
>LC-MS/MS for estradiol as well as the normal ELISA and they were >110%
>variation between the two readings. ELISA says my E2 is high, LCMS/MS
>says it's mid-range and fine. Plenty of other compounds can interfere
>with the enzyme linked assays. Would be pretty cool to have a
>constant monitoring of hormones but I don't see those tests ever
>miniaturizing anytime soon.
>
>I'm not even sure how the CGM works, is it all conductance based? Some
>electrical readout? Glucose is present at what, 100mg/mL? Those
>hormones are present at levels of nanograms to picograms per 10mL.
>
>On Fri, Apr 9, 2021 at 2:07 PM Tom De Medts <tdm...@gmail.com> wrote:
>>
>> Dear all,
>>
>> Is there anyone with experience in designing and implementing Continuous (blood) Analyte Monitoring like the now commonly used Continuous Glucose Monitor (CGM)?
>>
>> My question for you is based out of my own experience and frustration at fertility treatments. My spouse's hormone profile is very different from the ideal case, and it would be nice to be able to monitor her natural cyclic fluctuation in female hormones such as
>>
>> Estradiol
>> Follicle Stimulating Hormone
>> Luteinizing Hormone
>> Progesterone
>>
>> Online searches for continuous monitoring of these blood analytes were not available. Please note I am not referring to strip tests for use with pinprick blood tests or with urine samples. If I am wrong, and there are indeed continuous monitors for any of these hormones, please let us know.
>>
>> Else, if you have expertise / experience in any subject area(s) related to developing such CGM-like devices, could you please dumb it down for a non-technical audience and list
>>
>> what the low hanging fruits that could be easily achieved are
>> what the biological challenges are
>> what the tech challenges with measurements are
>> and anything else...
>>
>>
>> Thanks!
>> Tom
>>
>> --
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