Blog of Dr. William Matzner

William Matzner, MD, has been practicing medicine since 1989, Internal Medicine and Reproductive Immunology. M.D. with Honors from Baylor College of Medicine.

RISING COST OF HEALTHCARE IN THE UNITED STATES

By Dr. William Matzner

A recent article in the Wall Street Journal discussed the continued rise of healthcare cost in the US. By 2025 it is projected that healthcare costs will be at 18% of the GDP. Yet research has shown that among the Organization for Economic Cooperation and Development (OECD) member countries, the US has lower life expectancy at birth and higher mortality for death from respiratory disease, coronary artery disease and diabetes than the OECD average.


A key question becomes how can we decrease the cost of healthcare while simultaneously maintaining or improving the effectiveness of treatment programs? How can an organization health system, ACO, medical group, insurer, government, measure this so as to compare choices?


This is where Cost Effectiveness Analysis (CEA) can provide clear metrics to help determine how differing approaches to healthcare programming and delivery will affect policy change. In chronic diseases such as Diabetes and Coronary Artery Disease, Markov modeling has shown to be an ideal method to determine the cost effectiveness of different treatment approaches over time. One can compare a newer method or medication, or both, to a more standard treatment and see how the cost effectiveness accumulates over time.


Since CEA uses dollars per Quality Adjusted Life Years (QALY), one can quantitatively analyze how effective different treatments or methods are toward the particular disease. This way, policies can be chosen which not only cost less, but can help patients the most over time. It takes a subjective evaluation like effectiveness and turns it into a measurable metric researchers and policy developers can analyze.


The application of CEA using Markov modeling will provide clearer guidance as to how treatment policies should be elucidated, and in the long run can help reduce healthcare costs overall while maintaining and even improving the quality of healthcare delivery and outcomes. It can also be used to quantitatively monitor the effectiveness of new policies once implemented.


About William L. Matzner, M.D., PhD, FACP


Dr. William Matzner works in the area of healthcare economics consulting at Healthcare Analytics, LLC, in California. He graduated Phi Beta Kappa from Stanford University. He received his M.D. with Honors from Baylor College of Medicine. In 1988, he was the Solomon Scholar for Resident Research at Cedar Sinai Medical Center. Dr. Matzner subsequently was awarded a PhD in Neuro Economics from Claremont Graduate University. He is board certified in Internal Medicine and Palliative Medicine. He has researched and published extensively on the issue of reproduction and immunology in medical literature. He has been in private practice since 1989, specializing in Reproductive Immunology and Internal medicine.


Website: https://drwilliammatzner.com 

Consulting Website: https://healthcareanalytics.biz 

LinkedIn: https://www.linkedin.com/in/william-matzner-md-phd-mba-60219730 

Blog: https://drwilliammatzner.blogspot.com 

News: https://hype.news/dr-william-matzner/ 

News: https://hippocratesguild.com/dr-william-matzner 

News: https://medicogazette.com/dr-william-matzner

Dr. William Matzner, Simi Valley, California

Dr. William Matzner, Simi Valley, California

QUALITY ADJUSTED LIFE YEARS (QALY)—THE FORGOTTEN DENOMINATOR

By Dr. William Matzner

Author’s NOTE: The health promotion and wellness industry has often been asked to illustrate more quantitatively derived results if for no other reason than to justify budgetary increases based solely on the intuitive hypothesis that healthy people work better than unhealthy people. If better measured, wellness programming could stand to gain even broader support, larger budgets and a more prominent seat at the executive table. After all, who among those of us in the wellness business could argue against having a chief health officer in every corporation and organization. It really does make sense, but how many of those do you know? I, frankly, know none.


Cost Effectiveness Analysis allows us to present highly credible (that’s credible to the actual financial leaders in organizations) economic evaluation that does, as a number of you have asked, take into account actual clinical costs along with more qualitative factors as well. That’s what separates CEA from ROI, the ability for a group of critical evaluators to agree on a range of measures, apply both real and assumed “value” to those measures and then calculate the Cost Effectiveness of programming.


My between the lines read of may articles addressing ROI in wellness is that a fear exists among practitioners that when measured critically, wellness programming will come up short on a purely economic scale. I believe otherwise, that when measured critically, those holding the corporate purse strings will see greater value in wellness spending than they currently, and often grudgingly, allow. Further, well developed Cost Effectiveness Analysis will allow wellness professionals to better allocate spending among more qualitatively valuable and more quantitatively valuable programming.


Cost Effectiveness Analysis (CE Analysis) has been shown to be a useful tool in medicine to look at the true effectiveness of certain new (or even older) treatments. More recently I have written that it can prove to be a useful and flexible tool for looking at the effectiveness of various programs used in Corporate Health and Wellness programs. And as these corporate Health and Wellness programs become more common, CFOs want data to justify corporate spending for these programs.


At first glance, it appears that CE models developed for these programs involved simply looking at costs and decision tree analysis. However, the denominator of the CE analysis takes into account the QUALITY of life, not just the prolongation of life delivered by the treatment.


The Quality Adjusted Life Year  (QALY) is a year of life that is lived in perfect health. It takes into account the length of time and the health related quality of life (HRQL). The latter is given a numeric value between 0 and 1. This HRQL can be estimated by a survey or can be calculated from life tables and other published studies.  The value of HRQL has its roots in expected utility theory, a well developed economic theory.


A specific example may help. Let us say that we are measuring a wellness program that reduces stress. At first, someone could say that the cost difference in such a program is small with respect to productivity, days lost etc. and that a decision tree will not point you towards implementing such a program. BUT, this doesn’t take into account the difference in effectiveness. Let us say that a stress free life has a QALY of 1.0. However all the stress that one has at work may be severe enough to cause high blood pressure and release of adrenaline such that life would be less pleasurable and the QALY is reduced to 0.8. This would INCREASE the CE ratio by 20% (1/0.8). This leaves the non treatment side essentially costing 20% MORE, just because the quality is of life during stress is that much less.


The beauty and the flexibility of this approach is that we can turn subjective feelings and data about health and life into a NUMERIC value, and then use this to place in the denominator. 


For example, there has been much recent discussion about stress in the workplace and how reducing stress may be an important mission for corporate health and wellness programs. A stress value or measure can easily be built into the model so that a stressful life has less QALY. In this way the denominator becomes smaller and the CE ratio becomes larger (like adding a cost because the quality of life as a result is less).


The denominator in CE analysis, the QALY, can reflect pain and suffering as a result of problems like COPD or heart disease, the pain and debility of having surgery, or as we have alluded to, the mental and physical stress involved in a job. All these factors lead to a QALY less than one, making any treatment less effective once these subjective measures are taken into account.


There seem to be two camps of those interested in corporate health and wellness—one that wishes to look at the objective benefits of programs, and another that wishes to emphasis overall well being and less stress. Using the CE approach, we can quantify the subjective benefits and then produce a calculation to show (via the numbers) real measurable benefits to making such programs better. This will give even more validity to the usefulness of Corporate Health and Wellness programs and hopefully to their acceptance by CFOs and their counterparts.


About William L. Matzner, M.D., PhD, FACP


Dr. William Matzner works in the area of healthcare economics consulting at Healthcare Analytics, LLC, in California. He graduated Phi Beta Kappa from Stanford University. He received his M.D. with Honors from Baylor College of Medicine. In 1988, he was the Solomon Scholar for Resident Research at Cedar Sinai Medical Center. Dr. Matzner subsequently was awarded a PhD in Neuro Economics from Claremont Graduate University. He is board certified in Internal Medicine and Palliative Medicine. He has researched and published extensively on the issue of reproduction and immunology in medical literature. He has been in private practice since 1989, specializing in Reproductive Immunology and Internal medicine.


Website: https://drwilliammatzner.com

Consulting Website: https://healthcareanalytics.biz

LinkedIn: https://www.linkedin.com/in/william-matzner-md-phd-mba-60219730

Blog: https://drwilliammatzner.blogspot.com

News: https://hype.news/dr-william-matzner/

News: https://hippocratesguild.com/dr-william-matzner

News: https://medicogazette.com/dr-william-matzner 

Dr. William Matzner, Simi Valley, California

Dr. William Matzner, Simi Valley, California

MONITORING THE SUCCESS OF EXISTING HEALTHCARE PROGRAMS

By Dr. William Matzner

 

In the modern days of limited healthcare resources and decreased insurance reimbursements, it is not only helpful for healthcare organizations to analyze how new programs affect them economically, but also very useful to monitor the economic outcome of existing healthcare programs or treatments.


I was asked to analyze an existing disease management program by a large healthcare organization. They had developed a disease management program for COPD and wished to know if it was economically sound to continue this program.


I concluded that the most thorough way to evaluate this program was to use a Cost Effectiveness Markov Model. These models are excellent for looking at chronic on going conditions such as COPD. There are three possible disease states: Stable, somewhat sick and visiting urgent care, very sick and requiring hospitalization.


We were able to calculate not only costs associated with each state but also the quality of life as expressed in quality adjusted life years (QALY). The program was analyzed using incremental cost effectiveness ratio (ICER). 


The conclusion was that the program was successful by a significant amount, and furthermore that the savings was due to significant cost decrease in hospitalization of COPD patients involved in the program. Thus CEA can not only evaluate existing programs, but guide us into how those programs prove their effectiveness. CEA is starting to show its increased versatility in the modern healthcare economic environment. 


About William L. Matzner, M.D., PhD, FACP 


Dr. William Matzner works in the area of healthcare economics consulting at Healthcare Analytics, LLC, in California. He graduated Phi Beta Kappa from Stanford University. He received his M.D. with Honors from Baylor College of Medicine. In 1988, he was the Solomon Scholar for Resident Research at Cedar Sinai Medical Center. Dr. Matzner subsequently was awarded a PhD in Neuro Economics from Claremont Graduate University. He is board certified in Internal Medicine and Palliative Medicine. He has researched and published extensively on the issue of reproduction and immunology in medical literature. He has been in private practice since 1989, specializing in Reproductive Immunology and Internal medicine.


Website: https://drwilliammatzner.com 

Consulting Website: https://healthcareanalytics.biz 

LinkedIn: https://www.linkedin.com/in/william-matzner-md-phd-mba-60219730 

Blog: https://drwilliammatzner.blogspot.com 

News: https://hype.news/dr-william-matzner/ 

News: https://hippocratesguild.com/dr-william-matzner 

News: https://medicogazette.com/dr-william-matzner

Dr. William Matzner, Simi Valley, California

Dr. William Matzner, Simi Valley, California

REVENUE GENERATION IN THE OUTPATIENT SETTING

By Dr. William Matzner

Unlike other forms of economics, in healthcare, one cannot create increased demand for healthcare de novo as people do not seek healthcare professionals unless they are sick or injured. Therefore the pool of potential revenue is essentially fixed by the nature of various diseases and/or injuries. The problem that was suggested to me is that building a new surgery center will require much thought because the patients will come from local referrals and insurance companies, and not from a network of local physicians as had been done previously. However, the conversion of this potential revenue into increased demand for the surgery center is the key problem to solve before they would proceed with construction of the center.


Cost Effectiveness Analysis (CEA) presents a convenient and accurate way to compare revenue from physician referral vs from local and insurance referrals. One branch can compare the cost of generating the referrals from a physician referral network and its effectiveness in bringing in patients vs a branch, showing the costs in generating revenue using local marketing and insurance networks. The result will give a good idea if this new type of revenue generation is effective enough to justify the investment into a new surgery center.


CEA provides a unique and rigorous way to compare what at first appears to be apples vs. oranges. It can provide quantitative results that can help in deciding the feasibility of new investments for the healthcare organization.


About William L. Matzner, M.D., PhD, FACP


Dr. William Matzner works in the area of healthcare economics consulting at Healthcare Analytics, LLC, in California. He graduated Phi Beta Kappa from Stanford University. He received his M.D. with Honors from Baylor College of Medicine. In 1988, he was the Solomon Scholar for Resident Research at Cedar Sinai Medical Center. Dr. Matzner subsequently was awarded a PhD in Neuro Economics from Claremont Graduate University. He is board certified in Internal Medicine and Palliative Medicine. He has researched and published extensively on the issue of reproduction and immunology in medical literature. He has been in private practice since 1989, specializing in Reproductive Immunology and Internal medicine.


Website: https://drwilliammatzner.com 

Consulting Website: https://healthcareanalytics.biz 

LinkedIn: https://www.linkedin.com/in/william-matzner-md-phd-mba-60219730 

Blog: https://drwilliammatzner.blogspot.com 

News: https://hype.news/dr-william-matzner/ 

News: https://hippocratesguild.com/dr-william-matzner 

News: https://medicogazette.com/dr-william-matzner

Dr. William Matzner, Simi Valley, California

Dr. William Matzner, Simi Valley, California

MONITORING AND BUDGETING IN THE NEW HEALTHCARE ENVIRONMENT

By William Matzner, MD

The healthcare delivery environment has changed dramatically over the last several years. Most notably is the emphasis on appropriate limitation of medical resources to those patients that truly require it by set criteria. Healthcare organizations now face unique challenges in this new environment to deliver appropriate and quality healthcare yet remain profitable. How can they determine if what they are doing is economically beneficial? Should they continue the same programs and how much money should they devote to each program to remain profitable? How can they determine this analytically?


This is a perfect scenario where cost effectiveness analysis (CEA) can provide the appropriate guidelines to make good economic decisions. In CEA, one sets up a decision tree with two or more scenarios to compare which scenario (branch) is the best economically. CEA also has the added advantage of building the effectiveness of each decision branch into the model.


For example, suppose that your organization has a CHF disease management program as a supplement to the physician’s offices to help manage these chronically ill patients. A CEA decision tree can compare the costs to maintain CHF patients without the program, versus with the program. If the patients are clinically better with the program, this can be built into the model using Quality Adjusted Life Years (QALY). A CEA model can tell how much savings one program can bring versus another program or no program at all. This information can help in not only deciding whether to keep such a program, but also how much one can invest in the program for economic benefit to the healthcare organization. This can be critical to budgeting for subsequent years.


This is only one example of how CEA can help healthcare organizations in medical decision making and budgeting of existing healthcare programs.


About William L. Matzner, M.D., PhD, FACP


Dr. William Matzner works in the area of healthcare economics consulting at Healthcare Analytics, LLC, in California. He graduated Phi Beta Kappa from Stanford University. He received his M.D. with Honors from Baylor College of Medicine. In 1988, he was the Solomon Scholar for Resident Research at Cedar Sinai Medical Center. Dr. Matzner subsequently was awarded a PhD in Neuro Economics from Claremont Graduate University. He is board certified in Internal Medicine and Palliative Medicine. He has researched and published extensively on the issue of reproduction and immunology in medical literature. He has been in private practice since 1989, specializing in Reproductive Immunology and Internal medicine.


Website: https://drwilliammatzner.com 

Consulting Website: https://healthcareanalytics.biz 

LinkedIn: https://www.linkedin.com/in/william-matzner-md-phd-mba-60219730 

Blog: https://drwilliammatzner.blogspot.com 

News: https://hype.news/dr-william-matzner/ 

News: https://hippocratesguild.com/dr-william-matzner 

News: https://medicogazette.com/dr-william-matzner

William Matzner, MD, Simi Valley, CA

William Matzner, MD, Simi Valley, CA

HEALTH INFORMATION TECHNOLOGY

By Dr. William Matzner

The use of health information technology (HIT) has exploded over the last several years. It is now standard of care in most facilities to use electronic medical records for most all patient encounters. In the field of radiology, digital technology has lead to x-rays and CT scans being accessed on computers versus the days of the old radiograph being examined on a light box. Furthermore, access of these records is much easier so that all practitioners involved in the care of the patient can readily examine them.
 

The use of this technology comes at a very large cost in the development of software, and the use of computer hardware and cloud systems to implement.  Furthermore, there is cost in time and training to learn and utilize  this technology.  When a new system is introduced, how can one tell if the time and complexity to learn and implement the system is worth doing because of the increase benefits in the efficiency and the ability to use medical information? How can one determine if it is a good decision to implement a new technology or continue with the existing system and  medical records program?
 

The analysis of Broad Data, using  cost-effectiveness analysis, can give much clarity to such a decision.   Using a decision tree model, various aspects of how the HIT affects patient outcomes and decision making can be analyzed and quantified. It looks not only at the costs to the patient, but also incorporates how the decision impacts the health of the patient. Thus, using this analysis can assist on figuring how best to proceed with information gathering and sharing, and how that will impact the patient. It can quantify subjective feelings about how the HIT is implemented and its  usefulness, thereby opening up the possibility to have much better informed decision.
 

Healthcare has entered a new age. In some ways technology appears to have taken over healthcare, but by cleverly analyzing the best way to do this using cost effectiveness analysis can be of great benefit to patients.

About William L. Matzner, M.D., PhD, FACP
 

Dr. William Matzner works in the area of healthcare economics consulting at Healthcare Analytics, LLC, in California. He graduated Phi Beta Kappa from Stanford University. He received his M.D. with Honors from Baylor College of Medicine. In 1988, he was the Solomon Scholar for Resident  Research at Cedar Sinai Medical Center. Dr. Matzner subsequently was awarded a PhD in Neuro Economics from Claremont Graduate University. He is board certified in Internal Medicine and Palliative Medicine. He has  researched and published extensively on the issue of reproduction and immunology in medical literature. He has been in private practice since 1989, specializing in Reproductive Immunology and Internal medicine. 
 

Website: https://drwilliammatzner.com
Consulting Website: https://healthcareanalytics.biz
LinkedIn: https://www.linkedin.com/in/william-matzner-md-phd-mba-60219730
Blog: https://drwilliammatzner.blogspot.com
News: https://hype.news/dr-william-matzner/
News: https://hippocratesguild.com/dr-william-matzner
 News: https://medicogazette.com/dr-william-matzner 

Dr. William Matzner, Simi Valley, California

Dr. William Matzner, Simi Valley, California

High Fecundity Rates Following IVF and Embryo Transfer

In Antiphospholipid Antibody Seropositive Women Treated with Heparin and Aspirin

This is an excerpt of an article originally published in Human Reproduction and was co-authored by Dr. William Matzner.  The full article is available here.


INTRODUCTION


One of the great endeavours facing reproductive medicine is to improve pregnancy rates following in-vitro fertilization (IVF) and embryo transfer. Patients undergo IVF and embryo transfer for infertility secondary to organic pelvic disease, ovarian dysfunction, male factor, and immunological and unexplained aetiologies. It has been well documented that fertilization rates by assisted reproductive technologies are high (Lopata et al., 1982), yet the North American national IVF/embryo transfer birth rate for the year ending December 1991 was only 15.2% per egg retrieval (Society for Assisted Reproductive Technology, 1993). Autoantibodies have been detected in humans and other animals who have failed to conceive despite repeated attempts at IVF/embryo transfer. One such study has implicated antibodies to negatively charged phospholipids in unsuccessful IVF/embryo transfer cycles (Fisch et al., 199l). An increased prevalence of antiphospholipid antibodies (APA) has also been demonstrated in patients diagnosed with pelvic endometriosis (Gleicher et al., 1987). This has led to speculation that autoimmune processes similar to those known to be associated with recurrent pregnancy wastage may compromise embryo implantation following IVF/embryo transfer.


Several mechanisms have been proposed to explain how APA contribute to pregnancy wastage: platelet membrane and/ or endothelial cell wall damage may initiate the clotting cascade, and inhibition of prostacyclin and inability to activate protein C (an endogenous anticoagulant) may contribute to a hypercoagulable state (Harris et al., 1985). More recent work has demonstrated that several negatively charged APA, notably antiphosphoserine and antiphosphoethanolamine, interfere with the formation of syncytiotrophoblasts from cytotrophoblasts (Rote et al., 1992). This latter mechanism may also play a significant role in IVF/embryo transfer, as it emphasizes the function of phospholipids as adhesion molecules modulating the process of implantation. Interference with these adhesive properties may preclude implantation altogether or result in spontaneous abortions.


A study was undertaken to evaluate the effect of APA on women undergoing IVF/embryo transfer so as to determine (i) the prevalence of APA seropositivity in women with organic pelvic disease (i.e. post-surgical adhesions, endometriosis and/or pelvic inflammatory disease), compared to women whose infertility was not associated with tissuedamaging conditions (e.g. male factor and/or unexplained infertility), (ii) whether APA seropositivity adversely affects implantation and pregnancy rates with IVF/embryo transfer, and (iii) whether combined treatment with heparin and aspirin (H/A) improves ongoing clinical pregnancy rates in seropositive women who undergo IVF/embryo transfer.


MATERIALS AND METHODS


Patient population


We evaluated 429 women <40 years of age who underwent IVF/ embryo transfer at the Pacific Fertility Medical Centers in California, during the 30 month period commencing January 1, 1992 through June 30, 1994 in order to assess the relationship between APA seropositivity and the cause of infertility. The assessment of outcome following IVF/embryo transfer was confined to those cycles of treatment which immediately followed the diagnosis of APA status. Patients were divided into two groups: group 1 comprised 365 women with organic pelvic disease. Male factor infertility was absent in all cases. This group was further subdivided according to diagnosis as follows: group 1A comprised 79 women with endometriosis and of these, 52 (66%) women were APA seropositive; group 1B comprised 187 women who underwent IVF/embryo transfer for infertility due to pelvic inflammatory disease, and of these 85 (45%) women were APA seropositive; group 1C comprised 99 women who underwent IVF/embryo transfer for infertility due to abdominal/pelvic adhesions unassociated with prior pelvic inflammatory disease or endometriosis and 57 (58%) of these women were APA seropositive.

Group 2 comprised 64 women whose infertility was not associated with female pelvic pathology. The cause of infertility in this group was an ‘isolated male factor’ in 49 of these women and was ‘unexplained’ in 15 cases. Nine (14%) women in group 2 were APA seropositive.

The diagnosis of ‘isolated male factor infertility’ required the detection of < 10 x 106/ml motile spermatozoa on semen analysis in the absence of any identifiable female cause for infertility. Organic pelvic pathology was diagnosed or excluded by any combination of hysterosalpingography, laparoscopy and/or laparotomy. All women in the study had normal uterine cavities as observed at hysteroscopy. Women with thyroid dysfunction or hyperprolactinaemia were treated appropriately prior to commencing IVF/embryo transfer cycles.


Laboratory evaluation


All women were required to undergo serum follicle stimulating hormone (FSH) and oestradiol measurements (by radioimmunoassay) on the second or third day of a preceding menstrual cycle and were only included in this study if the FSH and oestradiol concentrations were < 15 mIU/ml and 40 pg/ml respectively. These women also underwent concomitant APA testing using an enzyme-linked immunosorbent assay for antibodies to six phospholipid epitopes (cardiolipin, phosphoserine, phosphoglycerol, phosphoethanolamine, phosphatidic acid and phosphoinositol), as previously described (Matzner et al, 1994). Cervical swabs and cultures were obtained tor Ureaplasma urealyticum as well as DNA probes for Chlamydia and Gonococcus. Male partners underwent semen evaluations which included sperm counts, motility, morphology and culture for pathogenic organisms. In addition, both women and men had sperm antibody serologies performed using the indirect immunobead test.


Treatment


Since women of a similar age with organic pelvic disease in the absence of male factor are expected to have comparable clinical pregnancy rates following IVF/embryo transfer attempts, evaluation of treatment with H/A was limited to patients in group 1. Antiphospholipid antibody seropositivity was defined by the detection of any concentration of APA in the IgG, IgM and/or IgA immunoglobulin fraction. There were 194 IVF/embryo transfer cycles performed on APA seropositive women. Of these, a total of 169 women received heparin sulphate [Lyphomed, Deerfield, Illinois, 60015; (5000 units s.c.)] twice daily, along with aspirin [Bayer, Division of Sterling Winthrop Inc, New York, NY 10016; (81mg)] orally once a day and there were 25 APA seropositive women who did not receive H/A. Treatment with H/A commenced with the initiation of ovarian stimulation on cycle day 2 to be continued through the 34th week of pregnancy. A luteal phase pituitary gland ‘down-regulation’ protocol using a gonadotrophin-releasing hormone agonist in conjunction with gonadotrophins was employed to achieve optimal ovarian stimulation as previously described (Feinman et al., 1993). Heparin was temporarily withheld after the morning administration on the day prior to oocyte retrieval and aspirin was withheld 2 days prior to this procedure (i.e. from the day of human chorionic gonadotrophin administration). Both heparin and aspirin therapy were reinitiated immediately following transvaginal ultrasound-guided oocyte retrieval. All patients undergoing H/ A therapy had normal activated partial prothrombin times, serum glutamic-oxalacetic transaminase and serum glutamic-pyruvic transaminase concentrations and normal red blood cell and platelet counts prior to initiating treatment. These tests were repeated at 2 week intervals for 2 months and thereafter at monthly intervals until termination of the medication regimen.


Endpoint


The endpoint was defined as either a viable pregnancy or delivery. The diagnosis of a viable pregnancy was based on sonographic confirmation of fetal cardiac activity.


Statistical methods


Comparisons of individual proportions in any two treatment groups were carried out using Fisher’s exact test. A collective test for treatment over several subgroups, such as groups 1A, 1B, and 1C in Table II, was made using the logarithmic regression model proposed by Cox (1972). The estimates and confidence limits obtained by this technique are computed from the complete data, and not simply from the marginal totals.


RESULTS


Table I illustrates that there was no evidence of systematic differences in the mean ages, ovarian stimulation protocols employed and the number of embryos transferred per IVF attempt among the group of women with organic pelvic pathology, male factor and unexplained infertility. There was, however, evidence that women in group l had a higher prevalence (P < 0.001) of APA seropositivity (53%) than women in group 2 (14%).

To determine whether APA seropositivity adversely affected IVF/ embryo transfer outcome, the pregnancy rates of untreated APA seropositive women were compared with those for APA seronegative women, following one IVF/embryo transfer cycle performed on group 1 patients, in the cycle that followed the diagnosis of the women’s APA status (see Table II). However, there was no firm statistical evidence of differential pregnancy rates. The ratio of pregnancy rates (APA- /APA+) was estimated as 1.66 with 95% confidence limits of 0.58 and 4.72, which embraced the ‘null hypothesis’ value of 1.0. The small number of untreated APA + women no doubt contributed to this failure to find evidence of an effect.

There was statistical evidence that the pregnancy rate in H/ A-treated APA seropositive women (49%) was significantly higher (P < 0.05) than for untreated APA seropositive women (16%). The logarithmic regression estimated the ratio of pregnancy rates (treated/untreated) as 3.02, with 95% confidence limits of 1.09 and 8.40); limits which do not embrace the ‘null hypothesis’ value of 1.0. The viable pregnancy rates per IVF/embryo transfer cycle, stratified by subgroups of organic pelvic pathology, are presented in Table II.


The pregnancy rate of the APA seropositive treatment group treated with heparin and aspirin (49%) was also significantly higher (P < 0.001) than that obtained from the APA seronegative group (27%). The ratio of pregnancy rates (APA + /APA-) was estimated as 1.79, with 95% confidence limits of 1.24 and 2.59, providing convincing evidence of the effect.


Rest of the article can be found at the link provided above. 


About William L. Matzner, M.D., PhD, FACP 


Dr. William Matzner works in the area of healthcare economics consulting at Healthcare Analytics, LLC, in California. He graduated Phi Beta Kappa from Stanford University. He received his M.D. with Honors from Baylor College of Medicine. In 1988, he was the Solomon Scholar for Resident Research at Cedar Sinai Medical Center. Dr. Matzner subsequently was awarded a PhD in Neuro Economics from Claremont Graduate University. He is board certified in Internal Medicine and Palliative Medicine. He has researched and published extensively on the issue of reproduction and immunology in medical literature. He has been in private practice since 1989, specializing in Reproductive Immunology and Internal medicine.


Website: https://drwilliammatzner.com

Consulting Website: https://healthcareanalytics.biz

LinkedIn: https://www.linkedin.com/in/william-matzner-md-phd-mba-60219730

Blog: https://drwilliammatzner.blogspot.com

News: https://hype.news/dr-william-matzner/

News: https://hippocratesguild.com/dr-william-matzner

News: https://medicogazette.com/dr-william-matzner

Dr. William Matzner, Simi Valley, CA

Dr. William Matzner, Simi Valley, CA

Treatment of IVF Patients with Antithyroid Antibodies

Combined Heparin/Aspirin and Immunoglobulin G. Therapy

 

This is an excerpt of an article originally  published in American Journal of Reproductive Immunology and was  co-authored by Dr. William Matzner.  The full article is available here.


INTRODUCTION


A  relationship between antithyroid antibodies (ATA) and reproductive  failure has been established.  In 1990, Stagnaro-Green evaluated a  selected obstetric population with a prior history of poor reproductive  performance, and was able to show a relationship between antithyroid  antibodies and miscarriage.  (1).  This was subsequently confirmed by  Glinoer, et al. in 1991 (2).  It was later demonstrated that women who  have an increased concentration of antithyroid antibodies and recurrent  pregnancy loss do not necessarily demonstrate anticardiolipin antibody  (3). Recently, Geva, et al. demonstrated that more than 20% of 78  patients undergoing IVF for mechanical or unexplained infertility tested  positive for antithyroid antibodies, and 12% were positive for  antiovarian antibodies.  Of note, is the fact that all patients in that  study were clinically euthyroid with no history of having been medicated  for hypothyroidism (4).  This data suggest that antithyroid antibodies  may be independent markers for reproductive failure.


It has been  suggested that the existence of antithyroid antibodies, before or during  early pregnancy may reflect activated T cell function, which in turn  may be related to TH1 lymphocytes (3,5). In designing this study, we  wished to examine the efficacy of only one variable (the use of IVIg) on  outcome in IVF patients who demonstrated thyroid antibodies.  Because  of the recent controversy over the use of aspirin and heparin in  patients undergoing IVF (8, 9), we elected to treat all patients with  aspirin and heparin, thereby eliminating the potential that this  variable could have an impact on outcome results when studying the  effects of IVIg on these patients.


MATERIALS AND METHODS


PATIENTS


A  prospective study was undertaken to evaluate whether reatment with  Heparin/Aspirin alone versus combined H/ A + IVIg would influence IVF  success rates.


Eighty two (82) women < 40 years of age, who  tested positive for ATA, but negative for antiphospholipid antibodies  (APA) were randomly placed into two groups in a non-discriminating quasi  alternating fashion.  Cases of male infertility, ovum donation, and  gestational surrogacy were excluded.  Group A comprised 37 women who  received H/A alone while Group B consisted of 45 women who received H/A  in combination with intravenous immunoglobulin G (IVIg – Gammimune,  Bayer Biological or Venoglobulin, Alpha Therapeutic Corp) 7-14 days  prior to embryo transfer.


Patients who had abnormally low plasma  levels of IgA were considered to be at risk for the development of  anaphylaxis and were selectively medicated with antihistamines and  corticosteroids prior to and during the 2-3 hour IVIg infusion.  A  second infusion of IVIg was given upon the chemical diagnosis of  pregnancy through quantitative serum HCG measurement and a final IVIg  infusion was performed upon ultrasound confirmation of a viable  pregnancy (between the 6th and 7th gestational week).  All patients  underwent controlled ovarian hyperstimulation (COH) using premenstrually  administered gonadotropin releasing hormone agonist (lupron-Tapp  pharmaceuticals), followed by menotropin therapy, as previously  described (7).  The measurement of APA’s was performed as previously  described by Matzner, et al. (8).


Antithyroid antibody positivity  (ATA+) was defined by the detection of antithyroglobulin and/or  antimicrosomal antibodies as measured by the QUANTA Lite Thyroid T and  Thyroid M ELISA assay from INOVA Diagnostics (San Diego, CA).  Briefly,  100 microliters of prediluted controls or diluted samples were added to  the microwell plates (which were coated with thyroglobulin or microsomal  antigen at the factory), and incubated at room temperature for 30  minutes.  The plates were washed in a wash buffer three times, and 100  microliters of HRP Conjugate was added to each well. The plates were  then incubated for another 30 minutes.  The plates were again washed  three time,s and 100 microliters of TMB Chromogen was added to the  wells, and incubated for 30 minutes. At that time, 100 microliters of  stopping solution was added, and the absorbance read at 450 nm, using  550 nm as a reference wavelength.  The published relative sensitivity  for this assay is 96.8%, and the relative specificity is 94.7%.


DETERMINANTS OF OUTCOME


The  number of babies born per transferred embryo, was determined in order  to provide a measure of the viable implantation rate.  Multiple births  and miscarriages were documented.  A successful IVF outcome was defined  as a live birth.


STATISTICAL METHODS


Data  was placed into two – by – two Tables: And analysis between and within  groups was performed using the Chi Squared Test for significance.  P  values below 0.05 were considered to indicate statistical significance.   Analysis was performed using the CHITEST and CHIINV functions for  Microsoft Excel 97 for Windows.


Rest of the article can be found at the link provided above.


About William L. Matzner, M.D., PhD, FACP 


Dr.  William Matzner works in the area of healthcare economics consulting at  Healthcare Analytics, LLC, in California. He graduated Phi Beta Kappa  from Stanford University. He received his M.D. with Honors from Baylor  College of Medicine. In 1988, he was the Solomon Scholar for Resident  Research at Cedar Sinai Medical Center. Dr. Matzner subsequently was  awarded a PhD in Neuro Economics from Claremont Graduate University. He  is board certified in Internal Medicine and Palliative Medicine. He has  researched and published extensively on the issue of reproduction and  immunology in medical literature. He has been in private practice since  1989, specializing in Reproductive Immunology and Internal medicine. 


Website: https://drwilliammatzner.com
Consulting Website: https://healthcareanalytics.biz
LinkedIn: https://www.linkedin.com/in/william-matzner-md-phd-mba-60219730
Blog: https://drwilliammatzner.blogspot.com
News: https://hype.news/dr-william-matzner/
News: https://hippocratesguild.com/dr-william-matzner
 News: https://medicogazette.com/dr-william-matzner

Dr. William Matzner, Simi Valley, CA

Dr. William Matzner, Simi Valley, CA

Use of Combined Heparin/Aspirin and IVIg Immunotherapy

In the Treatment of Recurrent IVF Failure Associated with Antiphospholipid Antibodies

 

This is an excerpt of an article originally  published in American Journal of Reproductive Immunology and was  co-authored by Dr. William Matzner.  The full article is available here.


INTRODUCTION


It  has been demonstrated that antiphospholipid antibodies (APA) play a  role in reproductive failure including recurrent pregnancy loss (1,2,3),  unexplained infertility (1), pregnancy related hypertension (4,5) and  intrauterine growth retardation (4).  Other studies (5,6,7) link APA to  In Vitro Fertilization (IVF) or Embryo Transfer (ET) failure.  We  previously reported on a negative correlation between APA positivity and  IVF outcome and established a therapeutic relevance for the selective  administration of mini-dose Heparin/Aspirin therapy (H/A) (8). In a  subsequent study we demonstrated that IVIg was beneficial in a subset of  women with a specific APA profile undergoing IVF (9).  Coulam et. al,  reported that the use of IVIg prior to IVF resulted in a 56% success  rate among a limited number of patients with multiple failed IVFs (12).   The purpose of this study was to help identify criteria for the  administration of IVIg in patients who suffered repeated IVF failure.   Due to recent controversy regarding the use of H/A in patients  undergoing IVF (15), we elected to treat all patients with these drugs  eliminating the potential that this variable could impact outcome  results when studying the effects of IVIg on these patients.


MATERIALS AND METHODS


PATIENT POPULATION


Eighty  nine (89) consecutive women who fulfilled the study criteria were  included in this study. The inclusion criteria were a) age <36 years,  b) four or more failed IVF/ET, c) no male infertility, d) no ovum  donation, e) no gestational surrogacy and, f) serum FSH concentration of  <15 mIU/ml and a plasma E2 of <70 pg/ml on cycle day three.  All  patients received gonadotrophin releasing hormone agonist (Lupron, Tapp  Pharmaceuticals) for luteal phase pituitary down regulation, followed by  menotropin therapy as previously described (10).  Starting on day two  of controlled ovarian hyperstimulation, each patient received aspirin 81  mg po qd, and heparin 5000 U sq bid.  In addition, each patient  received 20 gm of intravenous immunoglobulin (IVIg- Gammimune, Bayer  Biological or Venoglobulin, Alpha Therapeutic Corp) 3-10 days prior to  embryo transfer.


LABORATORY EVALUATION


All  women underwent serum follicle stimulating hormone (FSH) and estradiol  (E2) measurements (by radioimmunoassay) on day two or three of a prior  menstrual cycle. All women underwent APA testing using an enzyme linked  immunosorbent (ELISA) assay for IgM, IgG and IgA isotypes to six  phospholipid epitopes (cardiolipin-CL, phosphoserine-PS,  phosphoglycerol-PG, phosphoethanolamine-PE, phosphatidic acid-PA, and  phosphoinositol-PI) as described previously in detail (11). Borderline  positives were defined as >2 SD above the mean of normal controls,  and positive values were defined as >3 SD above the mean of normal  controls.  The control group for the APA assay consisted of  non-infertility patients who had no history of clinical or subclinical  autoimmune disease, or recurrent pregnancy loss.


Each time the  ELISA assay was performed, both known negative and positive controls  were run simultaneously for each isotype of every epitope.  (This was  important to assess the performance of the antigen coated on each plate,  the antibody conjugates, the pipetting technique, washing method,  incubation times, incubation temperature and substrate).Cervical or  semen specimens were cultured for Ureaplasma, Chlamydia and Gonococcus,  in all cases. Male partners all underwent semen analysis and both women  and men had sperm antibody serologies measured using the indirect  immunobead test.


DETERMINANTS OF OUTCOME


The  number of babies born per transferred embryo was determined in order to   provide a measure of the viable implantation rate.  Multiple births  and miscarriages were documented.  A successful IVF outcome was defined  as a live birth.


STATISTICAL METHODS


Data  was placed into two-by-two tables:  An analysis between and within  groups were performed using the Chi Square Test for significance. P  values below 0.05 were considered to indicate statistical significance.   Analysis was performed using the CHITEST and CHIINV functions for  Microsoft Excel 97 for Windows 95.
 

Rest of the article is available at the link provided above. 


About William L. Matzner, M.D., PhD, FACP


Dr.  William Matzner works in the area of healthcare economics consulting at  Healthcare Analytics, LLC, in California. He graduated Phi Beta Kappa  from Stanford University. He received his M.D. with Honors from Baylor  College of Medicine. In 1988, he was the Solomon Scholar for Resident  Research at Cedar Sinai Medical Center. Dr. Matzner subsequently was  awarded a PhD in Neuro Economics from Claremont Graduate University. He  is board certified in Internal Medicine and Palliative Medicine. He has  researched and published extensively on the issue of reproduction and  immunology in medical literature. He has been in private practice since  1989, specializing in Reproductive Immunology and Internal medicine. 


Website: https://drwilliammatzner.com
Consulting Website: https://healthcareanalytics.biz
LinkedIn: https://www.linkedin.com/in/william-matzner-md-phd-mba-60219730
Blog: https://drwilliammatzner.blogspot.com
News: https://hype.news/dr-william-matzner/
News: https://hippocratesguild.com/dr-william-matzner
News: https://medicogazette.com/dr-william-matzner
 

William Matzner, MD, Simi Valley, CA

William Matzner, MD, Simi Valley, CA

The Selective Use of Heparin/Aspirin Therapy

Management of Antiphospholipid Antibody Positive Women Undergoing In Vitro Fertilization

This is an excerpt of an article originally  published in American Journal of Reproductive Immunology and was  co-authored by Dr. William Matzner.  The full article is available here.


INTRODUCTION


Despite  the introduction of enhanced protocols for ovarian stimulation,  improved embryo culturing techniques, assisted hatching and  intracytoplasmic sperm injection, the national average birthrate per  completed cycle of In Vitro Fertilization (IVF) and Embryo Transfer (ET)  has minimally improved over the last few years and is still not much  above 20% per egg retrieval (1).  The successful implantation of a  morphologically normal embryo transferred to the uterus remains the  bottleneck in every IVF program.


For several years, researchers  have shown a link between abnormalities relative to the woman’s immune  system and recurrent pregnancy loss (2-5).  More recent data suggests  that the immunologic pathophysiology associated with recurrent pregnancy  loss and early implantation failure may be similar.  Clearly,  implantation failure at a preclinical stage is often misdiagnosed as  “infertility”.  Perhaps the term Failed Pregnancy Recognition (FPR)  would be more appropriate in such cases.  It is likely that immunologic  deficiency plays a significant role in a variety of implantation related  problems, including but not limited to; FPR, biochemical pregnancy,  blighted ovum and first trimester miscarriage (4-9).


Bustillo,  et al. reported a five fold increase in the prevalence of APA  seropositivity in 84 women who failed to conceive following the transfer  of twelve or more embryos over a number of IVF/ET cycles (10).  Sher,  et al. described a high prevalence of antiphospholipid antibodies (APA)  in women with pelvic organic disease who underwent in vitro  fertilization (IVF) and embryo transfer (ET), and demonstrated a three  fold improvement in clinical PR with the first IVF cycle when H/A was  administered to APA+ women under the age of 40 years (7), suggesting  that autoimmune mechanisms associated with early implantation failure  are potentially treatable.


It has been demonstrated that APA+  patients undergoing IVF benefit from H/A therapy (7), therefore, we  tested all IVF candidates prior to commencing their first IVF attempt.  Over the years, we noted a trend from the results in our clinic  suggesting that women who possessed IgG or IgM antibodies to  phosphoserine (PS) or phosphoethanolamine (PE), had lower pregnancy  rates than women with any other APA. With this observation, and Coulam,  et. al. reported success using intravenous immune globulin (IVIg) on  unselected patients who had failed several IVF attempts (11), we  attempted to establish specific criteria for which patients might  benefit from H/A along with IVIg. IVIg was felt to be an appropriate  immune modulator because it has been proven useful in a variety of  autoimmune disorders such as Kawasaki’s disease, idiopathic  thrombocytopenic purpura and Wiskott-Aldrich syndrome.  Although the  mechanism of action is unclear, it is believed that the anti-idiotype  antibodies in the IVIg play an immune modulating function (12).   The  specific objectives of this analysis are: 1) To determine whether the  effect of H/A therapy was influenced by the phospholipid (PL) epitope  against which the APA were directed as well as the gammaglobulin isotype  involved; and 2) To ascertain whether H/A treated, APA+ women who  failed to conceive following two consecutive IVF cycles of treatment,  would experience improved birthrates following the combined  administration of H/A and IVIg during the third consecutive IVF attempt,  and to establish if any particular APA type predicts which women may  benefit from IVIg therapy.


MATERIALS AND METHODS


A  study was undertaken, involving 687 APA+ women (age range 29-40 years,  mean age 36.25 years) who underwent IVF/ET at Pacific Fertility Medical  Center during a four year period commencing January 1992.  Cases of male  infertility, ovum donation and gestational surrogacy were excluded. The   data analysis was conducted in three phases.


Phase I


Six  hundred eighty seven (687) women who tested APA+ to one or more PL  epitope each underwent < 2 IVF cycles for a total of 1050 completed  treatment cycles.  All women were offered treatment with heparin and  aspirin.  Those who accepted were put into Group A and those that  declined were placed in Group B.  Six hundred three (603) of these women  (Group A) underwent a total of 923 IVF cycles of treatment where H/A  alone was administered, while the remaining 84 women (Group B) underwent  127 IVF cycles where H/A was not administered.


Phase II


We  evaluated whether IVF outcome following two consecutive cycles of H/A  therapy was influenced by the APA profile (i.e. the specific PL epitope  to which APA were directed and the associated gammaglobulin isotype).  Since the number of individual APA sub-profiles was quite large, the  sub-groups were too small to permit statistical comparison in patients  who had APA directed against multiple phospholipids. In addition, it  would be difficult to ascertain if one specific PL influenced outcome in  the presence of other PLs.   Accordingly, Group C represents those 322  women from Group A  who each tested positive to only one APA.


Phase III


Group  D represents one hundred twenty one (121) women from Group C  who did  not achieve viable pregnancies in Phase II (i.e. following two  consecutive IVF attempts), where immunotherapy was confined to H/A  alone.  These women received IVIg in combination with H/A during their  third consecutive IVF cycle.


LABORATORY EVALUATION


All  women underwent serum follicle stimulating hormone (FSH) and estradiol  (E2) measurements (by radioimmunoassay or enzyme assay) on day two or  three of a prior menstrual cycle.  Only those women who had a serum FSH  concentration of < 10mIU/ml and a plasma E2 of < 70pg/ ml on cycle  day three, were included in the study.  All women underwent APA testing  using an enzyme-linked immunosorbent assay for antibodies to the  following six phospholipid epitopes: cardiolipin (CL), phosphoserine  (PS), phosphoglycerol (PG), phosphoethanolamine (PE), phosphatidic acid  (PA), and phosphoinositol (PI), as previously described in detail (13).   Antiphospholipid antibody seropositivity (APA+) was defined by the  detection of APA measuring > two (2) standard deviations from the  mean to IgA, IgM and/or IgG isotypes.  Borderline values were defined as  >2 SD above the mean, and positive values were defined as >3 SD  above the mean of normal controls. The control group for the APA assay  consisted of non-infertility patients who had no history of clinical or  subclinical autoimmune disease, or recurrent pregnancy loss.


Each  time the ELISA assay was performed, both known negative and positive  controls were run simultaneously for each epitope and isotype.  This was  important to assess the performance of the antigen coated on each  plate, the antibody conjugates, the pipetting technique, washing method,  incubation times, incubation temperature and substrate.


Cervical  or semen specimens were cultured for Ureaplasma, Chlamydia and  Gonococcus, in all cases.  Male partners all underwent semen analyses to  exclude male factor infertility.


DETERMINANTS OF OUTCOME


The  number of babies born per transferred embryo, was determined in order  to provide a measure of the viable implantation rate.  Multiple births  and miscarriages were documented.  A successful IVF outcome was defined  as a live birth.


TREATMENT


All patients  underwent controlled ovarian hyperstimulation (COH) with menotropins,  preceded by pituitary down regulation with gonadotrophin releasing  hormone agonist (GnRHa) by a previously described protocol (14).
All  patients included in this study were APA+ and received aspirin 81 mg po  qd and heparin 5000 U sq bid, starting on day two of Controlled Ovarian  Hyperstimulation.  Heparin was withheld on the morning of egg retrieval,  and reinstated that same evening while aspirin was withheld from the  ninth day of menotropin stimulation and was reinstated on the evening  following egg retrieval.  H/A was discontinued if pregnancy did not  occur as evidenced by rising quantitative human chorionic gonatotropin  (HCG) blood levels measured respectively on the 8th and 10th day postET.  Patients with a positive HCG blood test continued with H/A treatment  through the diagnosis of a clinical pregnancy, 3-4 weeks post ET.  H/A  was continued until, at least the 10th gestational week.  H/A treatment  was monitored as previously described (7).


STATISTICAL METHODS


Data  was placed into two-by-two tables; and analyses between and within  groups were performed using the Chi Squared test for significance.  P  values below 0.05 were considered to indicate statistical significance.   Analysis was performed using the CHITEST and CHIINV functions of  Microsoft Excel 97 for Windows.


About William L. Matzner, M.D., PhD, FACP


Dr.  William Matzner works in the area of healthcare economics consulting at  Healthcare Analytics, LLC, in California. He graduated Phi Beta Kappa  from Stanford University. He received his M.D. with Honors from Baylor  College of Medicine. In 1988, he was the Solomon Scholar for Resident  Research at Cedar Sinai Medical Center. Dr. Matzner subsequently was  awarded a PhD in Neuro Economics from Claremont Graduate University. He  is board certified in Internal Medicine and Palliative Medicine. He has  researched and published extensively on the issue of reproduction and  immunology in medical literature. He has been in private practice since  1989, specializing in Reproductive Immunology and Internal medicine.


Website: https://drwilliammatzner.com
Consulting Website: https://healthcareanalytics.biz
LinkedIn: https://www.linkedin.com/in/william-matzner-md-phd-mba-60219730
Blog: https://drwilliammatzner.blogspot.com
News: https://hype.news/dr-william-matzner/
News: https://hippocratesguild.com/dr-william-matzner
News: https://medicogazette.com/dr-william-matzner
 

William Matzner, MD, Simi Valley, CA

William Matzner, MD, Simi Valley, CA

Antibodies to phosphatidylethanolamine & phosphatidylserine

Associated with increased natural killer cell activity in non-male factor infertility patients

This is an excerpt of an article originally  published in Human Reproduction and was co-authored by Dr. William  Matzner.  The full article is available here.


Introduction


Numerous  investigators have shown an increased prevalence of antiphospholipid  antibodies (APA) among infertile women. However, the exact relationship  between APA and infertility in general, and IVF specifically, remains an  enigma (Coulam, 1999). Four studies suggest that APA exert an adverse  influence on IVF outcome (Birkenfeld et al., 1994; Geva et al., 1994;  Sher et al., 1994, 1998a; Dmowski et al., 1995), while five others show  no such relationship (Gleicher et al., 1994; Birdsall et al., 1996;  Denis et al., 1997; Kowalick et al., 1997; Kutteh, 1997). Possible  explanations for the discrepancies include: (i) absence of  standardization in the assays used to measure APA; (ii) varying cut-off  points used to define positive versus negative results; (iii)  differences in the populations of patients studied; and (iv) the fact  that IVF, by its very nature, involves so many sensitive and complex  steps, as to render assessment of the influence of any single variable  on outcome, virtually impossible.


The authors have previously  reported a correlation between APA positivity and decreased IVF  pregnancy rates in cases of organic female and unexplained infertility,  which could not be established in cases of isolated male factor  infertility (Sher et al., 1994, 1998b). The IVF outcome in these  patients was significantly improved through administration of mini-dose  heparin/aspirin (H/A) therapy (Sher et al., 1994, 1998b). However we  noted that, in contrast to other phospholipid epitopes, in the presence  of IgG or IgM class antibodies against phosphatidylethanolamine (PE)  and/or phosphatidylserine (PS), H/A therapy alone was not found to be  beneficial (Sher et al., 1998b). In these patients, the addition of  empiric treatment with intravenous immunoglobulin G (IVIG) was able to  improve outcome in a subsequent IVF cycle (Sher et al., 1998a,b). The  therapeutic role of IVIG for treating reproductive failure is  controversial (Balasch et al., 1996; Christiansen, 1998; Daya et al.,  1998; Stephenson et al., 1998). However, proponents of its use for both  immunological spontaneous abortion and IVF failure have suggested that a  possible mechanism of action may be through down-regulation of NK cell  cytotoxicity (activity), thereby converting a hostile Thl endometrial  milieu to a trophoblast-friendly Th2 environment (DePlacido et al.,  1994).


The present study had two objectives. The first was to  evaluate the prevalence of APA and increased peripheral NK cell activity  (NKa) in IVF candidates with organic female indications (i.e.  endometriosis, pelvic adhesions) or unexplained infertility, compared  with a similar group of patients with isolated male factor infertility.  Second, given our previous experience of IVIG being beneficial for IVF  outcome in aPE/ aPS+ patients, as well as its reported down-regulatory  effect on NK cell activity, we attempted to evaluate the association of  the presence of antibodies against these specific phospholipid epitopes  with increased peripheral NK cell activity.


Materials and methods


Patient population


All  patients evaluated between December 1998 and June 1999 for treatment  with IVF-embryo transfer who were aged under 40 years, and had cycle day  3 FSH concentrations < 10 mIU/ml, were included in this  retrospective analysis. All of these patients were screened for  immunological abnormalities as part of a standard work-up. Indications  for IVF treatment included male factor, endometriosis, pelvic adhesions  and unexplained infertility with previous treatment failure. Patients  with a male factor and other female factors were classified in the  female factor group. Endometriosis patients encompassed all stages of  disease, but were mainly stages I and lI. Patients classified as  unexplained infertility were documented by laparoscopy to have patent  tubes, were free of pelvic adhesions and endometriosis, and had a normal  uterine cavity by hysteroscopy or hysterosalpingography. They had  normal ovulation, and there was no evidence of male factor or antisperm  antibodies. Not all patients evaluated subsequently underwent treatment  and therefore, no attempt was made in this study to correlate the  presence of APA or NKa with IVF outcome.


Laboratory evaluation


Assays  were performed by Reproductive Immunology Associates (Van Nuys, CA,  USA) and by University Health Sciences Laboratory (Chicago, IL, USA).  Patients were screened for the presence of antiphospholipid antibodies,  using an enzyme-linked immunosorbent assay (ELISA) for IgM, IgG and IgA  isotypes to six phospholipid epitopes [cardiolipin (CL),  phosphatidylserine (PS), phosphatidylethanolamine (PE), phosphatidic  acid (PA), phosphatidylglycerol (PG) and phosphatidylinositol (PI)], as  described previously in detail (Matzner et al., 1994).


The  control group for the APA assays consisted of 40 non-infertility  patients, aged between 25 and 45 years, who had no history of clinical  or subclinical autoimmune disease, or recurrent pregnancy loss. Using  the central limit theorem, the sampling distribution of the sample mean  was approximated by a normal probability distribution as the sample size  became `large' (defined as n > 30). Based upon this theorem,  borderline positives were defined as >2 SD above the mean of normal  controls, and positive values were defined as >3 SD above the mean  for normal controls. As is standard in the field of rheumatology, and as  defined by the American Society of Reproductive Immunology (Coulam et  al.. 1999), a positive assay in the presence of the proper clinical  history was used to define the autoimmune reproductive failure syndrome  in these patients.


Each time an ELISA assay was performed, both  known negative and positive controls were run simultaneously for each  isotype of every epitope. Positive controls were obtained from APL  Diagnostics (Louisville, KY, USA), and from serum samples in the  radioimmunoassay laboratory that were consistently over 2.0 optical  densities (OD). This was important to assess the performance of the  antigen coated on each plate, the antibody conjugates, the pipetting  technique, the washing method, the incubation times, the incubation  temperatures and the substrate. Intra-assay variation was addressed by  running each sample in duplicate with the final reported value being the  average of the two. The inter-assay assay coefficient of variation was  2.12%.


The determination of natural killer cell function was  performed by flow cytometry using a previously described technique (Kane  et al., 1996). Briefly, K562 cells were grown as stationary cultures at  37°C in 5% CO2. The cells were subcultured for 3 days before the assay,  to be certain that they were in log phase. Before use in the assay,  cells were incubated with 10 ill of 30 mmol/1 dioctadecyloxacarbocyanine  perchlorate (DiO) per ml for 20 min at 37°C, 5% CO2. Effector cells  aPE/aPS and NK cell were isolated from the buffy coat of heparinized  blood using the FicolHypaque centrifugation. Target cells at the  standard concentration and effector cells at various dilutions (1:1,  1:2, 1:4, 1:8) were added to create effector/target ratios from 50:1  down to 6.25:1. A total of 130 µl of propidium iodide (PI) was added to  the tubes, and the mixture was centrifuged for 30 s at 1000 g in order  to pellet target, effector cells and PI. Either interleukin-2 (IL-2) or  various concentrations of IVIG were added to the assay. and the mixture  was incubated overnight at 37°C, 5% CO2. Data were collected for  analysis on the Becton-Dickinson FACScan flow cytometer, using the  Consort30 (Becton-Dickinson Immunocytometry systems; BDIS) program and  Lysis software (BDIS). The spontaneous lysis was subtracted from the  actual lysis for each sample. Based upon the control population (noted  above), increased NK activity was defined as > 10% killing, with  increased killing activity in the presence of IL-2, and decreased  activity of at least 50% from the natural state in the presence of IVIG.


Statistical methods


Analyses  of differences within and between groups were performed using the  chi-square and Fisher's exact tests for significance where appropriate. A  P-value < 0.05 was considered statistically significant.


About William L. Matzner, M.D., PhD, FACP


Dr.  William Matzner works in the area of healthcare economics consulting at  Healthcare Analytics, LLC, in California. He graduated Phi Beta Kappa  from Stanford University. He received his M.D. with Honors from Baylor  College of Medicine. In 1988, he was the Solomon Scholar for Resident  Research at Cedar Sinai Medical Center. Dr. Matzner subsequently was  awarded a PhD in Neuro Economics from Claremont Graduate University. He  is board certified in Internal Medicine and Palliative Medicine. He has  researched and published extensively on the issue of reproduction and  immunology in medical literature. He has been in private practice since  1989, specializing in Reproductive Immunology and Internal medicine.


Website: https://drwilliammatzner.com
Consulting Website: https://healthcareanalytics.biz
LinkedIn: https://www.linkedin.com/in/william-matzner-md-phd-mba-60219730
Blog: https://drwilliammatzner.blogspot.com
News: https://hype.news/dr-william-matzner/
News: https://hippocratesguild.com/dr-william-matzner
News: https://medicogazette.com/dr-william-matzner 

Dr. William Matzner, Simi Valley, California

Dr. William Matzner, Simi Valley, California

Characterization of Antiphospholipid Antibodies

In Women with Recurrent Spontaneous Abortions

This is an excerpt of an article originally published in The Journal of  Reproductive Medicine and was co-authored by Dr. William Matzner.  The  full article is available here.


Introduction


It  is estimated that approximately 40% of women with systemic lupus  eythematosus (SLE) will have antibodies to negatively charged  phospholipid, with reported ranges of 30% to 70% having suffered  thrombotic events. In 1986 a group of women without known autoimmune  diseases who had recurrent spontaneous abortions (RSA) or vascular  thrombosis was described. These women had antibodies to a negatively  charged phospholipid, cardiolipin, with high titers primarily of the IgG  isotype. The mechanisms of action defined were platelet membrane  damage, endothelial wall injury, inhibition of prostacyclin and  inability to activate protein C; thus, RSA would occur via placental  vascular insufficiency.


In 1985 Harris showed that  anticardiolipin antibody (aCL) bound equally to all negatively charged  phospholipids. Subsequent studies that addressed issues of  antiphospholipid antibodies (aPLs) therefore assumed nondifferential  binding or concentrated only on aCL.In 1985 Lockshin et al demonstrated  that the level of aCL was useful as an early predictor of fetal distress  or death in patients with SLE. Recent work has implicated  antiphosphoserine antibody, predominantly of the IgM isotype, as an  inhibitor of placental formation and a causeof RSA.


In the study described below, aPLs were characterized in a group of women who have suffered recurrent fetal loss.


Materials and Methods


Patients


Three  hundred fifty-two patients with a history of two or more consecutive  spontaneous pregnancy losses were evaluated. They were premenopausal  (aged 2145; mean, 39), and all were recruited between March 1991 and May  1992. Women with collagen vascular disease were excluded. Phospholipid  antibodies of the IgM and IgG isotypes to cardiolipin,  phosphoethanolamine, phosphoinositol, phosphoserine, phosphatidic acid  and phosphoglycerol were measured.


Controls


The  control group consisted of 43 people without known immunologic or  rheumatologic diseases. None of the women in the control group had  suffered RSA or any other thromboembolic phenomena.


aPL Assay


The  assay used has been described previously. Briefly, six purified  phospholipids were coated separately on Immulon 2 96-well enzyme-linked  immunosorbent assay plates overnight. The plates were blocked the next  day with phosphate-buffered saline (PBS) and 10% newborn calf serum for  two hours and then washed (Biotech BT500) in PBS.


Fifty  microliters of patient serum was added to the appropriate wells and  incubated for one hour followed by a second wash with PBS. Alkaline  phosphatase-conjugated goat antihuman IgG and IgM was incubated for an  hour, then washed in PBS. Sigma Substrate 104 in diethanolamine buffer  was added to the wells and incubated for 30 minutes at 37°C, and the  reaction was stopped with NaOH. The trays were read in a BioTech BT2000  microtiter reader at 405 nm. Delta optical densities were calculated by  subtracting out the background (wells without the phospholipid  antigens).


The results were compared to the mean of the delta  optical densities for the control group. Positivity was defined as 3 SD  above the mean of the controls.


Results


The  prevalence of one or more antibodies to any of the six phospholipids  was 59.1% (208/352) in the study population. In the control group, only  4.6% (2/43) had a positive aPL.


Two hundred eight patients had 439  antibodies of the IgG or IgM isotype to the phospholipids. The most  frequently identified aPLs in order of decreasing frequency were to  phosphoserine, 20.5% (90/439); phosphoethanolamine, 19.1% (84/439);  phosphatidic acid, 18.7% (82/439); cardiolipin, 16.4% (72/439);  phosphoglycerol, 16.2% (71/439); and phosphoinositol, 9.1% (40/439). In  the two positive controls there were 2 anitibodies, both of the IgG  isotype, 1 each to cardiolipin and phosphatidic acid. In the RSA  patients, 75.2% (330/439) of the antibodies were of the IgM isotype, and  24.8% (109/439) were of the IgG isotype.


Of all of the patients  studied, 18.2% (64/352) had aCL versus 40.9% (144/352) with any other  combination excluding aCL. Of all the patients with any aPL, 30.8% (64/  208) were to cardiolipin. Eighty-one patients had antibodies to only one  epitope: 37.0% (30/81) were to phosphoethanolamine, 14.8% (12/81) to  phosphatidic acid and 16.0% (13/81) to cardiolipin. Of this group, 83.9%  (68) were IgM and 16.1% (13) were IgG isotypes.


The remainder of  the patients (132) had antibodies to multiple epitopes. They had 358  antibodies of the IgG or IgM isotype. In this group, in order of  decreasing frequency, were antibodies to phosphoserine, 22.9% (82/ 358);  phosphatidic acid, 19.6% (70/358); phosphoglycerol, 18.2% (65/358);  cardiolipin, 16.5% (59/358); phosphoethanolamine, 15.1% (54/ 358); and  phosphoinositol, 7.8% (28/358). In these patients, 73.2% (262/358) of  the antibodies were of the IgM and 26.8% (96/358) of the IgG isotype.


About William L. Matzner, M.D., PhD, FACP


Dr.  William Matzner works in the area of healthcare economics consulting at  Healthcare Analytics, LLC, in California. He graduated Phi Beta Kappa  from Stanford University. He received his M.D. with Honors from Baylor  College of Medicine. In 1988, he was the Solomon Scholar for Resident  Research at Cedar Sinai Medical Center. Dr. Matzner subsequently was  awarded a PhD in Neuro Economics from Claremont Graduate University. He  is board certified in Internal Medicine and Palliative Medicine. He has  researched and published extensively on the issue of reproduction and  immunology in medical literature. He has been in private practice since  1989, specializing in Reproductive Immunology and Internal medicine.


Website: https://drwilliammatzner.com
Consulting Website: https://healthcareanalytics.biz
LinkedIn: https://www.linkedin.com/in/william-matzner-md-phd-mba-60219730
Blog: https://drwilliammatzner.blogspot.com
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Dr. William Matzner, Simi Valley, CA

Dr. William Matzner, Simi Valley, CA

Immunology of Recurrent Spontaneous Abortion

Excerpt by Dr. William Matzner

This  is an excerpt of an article originally  published in The Female Patient and was co-authored by Dr. William  Matzner.  The full article is available here.


Immunology of Recurrent Spontaneous Abortion


Introduction


The  immunology of reproduction is a dynamic field, with data forthcoming  exponentially. Immune mechanisms are operative in infertility,  endometriosis, eclampsia/preeclampsia, miscarriage, and other aspects of  reproduction. This paper focuses on the immunology of recurrent  spontaneous abortion (RSA). Classically, a patient is considered to have  RSA if she has had three or more consecutive miscarriages, but many  clinicians are now evaluating couples after two consecutive losses.


The  causes of RSA have been classified as infection (1%), anatomic  abnormalities (5% to 10%), lutealphase defect (5% to 20%), chromosomal  abnormalities (7% to 50%), immune mechanisms (50%), and unknown (15%).  Some women have multiple reasons for RSA. A workup comprising  ultrasonography, hysterosalpingography, laparoscopy, endometrial biopsy,  parental and fetal chromosome analysis, cervical culture, and  progesterone testing would explain only about 50% of the pregnancy  losses. There is strong evidence that the remainder of miscarriages are  mediated by immune mechanisms.


The uterus is an enigma. Despite a  full complement of immunocompetent cells, it allows the fetal allograft  to thrive for 40 weeks. During pregnancy, the fetoplacental unit  orchestrates immune mechanisms via T and B Iymphocytes, natural killer  cells (NK), a variety of soluble immunoregulatory factors (cytokines),  and antibodies. To a significant degree, the interaction between  maternal and fetoplacental tissue and the immune system will determine  whether a pregnancy succeeds. Three antibodies are critically important  to pregnancy maintenance: maternal antipaternal leukocyte antibodies  (APLA) (ie, blocking antibodies), antiphospholipid antibodies (APA), and  antinuclear antibodies (ANA).


When the immune system is the cause  of miscarriage, the mother has a 30% chance of having a successful  pregnancy without intervention after 3 miscarriages, a 25% chance after 4  miscarriages, and a 5% chance after 5 miscarriages. With proper  treatment, the overall success rate has been reported at 70% to 85% in  parity  and agematched controls.


Antipaternal Leukocyte Antibodies


APLA  are antibodies that mask paternal human leukocyte antigens (HLA) found  on the fetus from maternal immune effector cells. Genes that code for  HLA or tissue type are located on chromosome 6. HLA consist of class I  and class II antigens. Class I antigens, which include the A, B, and C  loci, are found on all nucleated cells and platelets and are the only  HLA expressed on nonactivated T Iymphocytes. More recently, another  class I HLA, designated G, has been identified on cytotrophoblasts  versus syncytiotrophoblasts, which do not express any HLA. However,  studies using the polymerase chain reaction have shown that the  placental barrier is not impervious to tissue, so that maternal cells  have been found in the fetal circulation and fetal cells in maternal  circulation.


In the RSA couple, APLA levels should be ascertained  prior to conception using cell-flow cytometry. The husband’s Iymphocytes  are combined with the wife’s serum (which would contain APLA if  present), and incubated with fluorescent markers. The entire mixture is  placed into the cytometer, which utilizes laminar flow fluidics and  argon lasers. Under laser illumination, cells that have APLA attached  will fluoresce. The emission will be captured by photomultiplier tubes  and transferred to a computer that digitizes the signal.


Treatment  involves immunizing the mother with concentrates of paternal  Iymphocytes so that the signal is amplified approximately 10,000 times  the level normally seen in early pregnancy. Paternal leukocyte  immunization (PLI) treatments are usually administered 4 weeks apart.  Four weeks after the second immunization, the APLA level is remeasured.


Antiphospholipid Antibodies


Phospholipid  molecules are normal components of all cell membranes. Antibodies to  phospholipids have been implicated in numerous disease states,  generating much academic interest. APA are capable of vascular  compromise via damage to vascular endothelium and platelet membrane by  inhibiting prostacyclin (vasodilator) and interfering with the  activation of protein C. The result is increased platelet adhesion and a  relative rise in thromboxane (vasoconstrictor), resulting in a milieu  conducive to thrombotic events. In the uteroplacental circulation these  insults translate into fetal demise or intrauterine growth retardation.


With  each pregnancy loss, there is a 10% chance that the mother will develop  an antibody to a phospholipid molecule, and the effect is cumulative.  Most women with APA are asymptomatic, but some have underlying  autoimmune tendencies and should be evaluated appropriately. Although  there is a high incidence of APA in patients with systemic lupus  erythematosus (SLE), there is a significant population who have APA but  no other disease. The diagnosis assigned to patients with thrombotic  events in the presence of APA is primary antiphospholipid antibody  syndrome.


Treatment of APA involves the use of low-dose (baby)  aspirin and prophylactic heparin, which is a large molecule that cannot  cross the placenta. Heparin activates the formation of antithrombin III,  which interferes with the coagulation cascade. Although aspirin can  traverse the placenta, the dose is small and usually does not affect the  fetus. Aspirin inhibits cyclooxygenase and the formation of  thromboxanes, allowing prostacyclin to act unopposed. Treatment is more  effective when medication, if indicated, is started prior to conception  and continued throughout pregnancy.


Antinuclear  Antibodies


There  is an increased prevalence of RSA patients who demonstrate ANA compared  with parity- and age-matched nonaborters. What causes these antibodies  to be synthesized is currently under investigation, but there appears to  be a genetic susceptibility dictated by the HLA tissue type. This is  compounded by the production of autoantibodies like ANA with fetal  demise. The disease typically associated with ANA is SLE, which confers a  much higher miscarriage rate than that of the general population—  approaching 50% in patients with active disease. Although most women  with RSA do not fulfill the American College of Rheumatology criteria  for SLE, many exhibit lupus-like tendencies. Polyclonal B cell  activation appears to be more common in these patients. Although the  exact mechanisms whereby ANA contribute to miscarriage is unknown,  placental pathology studies reveal inflammatory changes in the uterine  and placental tissue (villitis) and vasculitis.


When ANA are  present in the context of RSA, prednisone is recommended to suppress the  inflammatory process and stabilize cell membranes. Prednisone does not  cross the placenta easily because it is highly bound to albumin, which  is a large protein molecule. In addition, the placenta contains  Beta2-dehydrogenase, which metabolizes this steroid. Suppression of the  fetal adrenal axis has not been reported. When indicated, prednisone is  instituted prior to conception. With treatment, there is an 80% to 85%  chance of successful term pregnancy. As the body is dynamic, antibody  levels may change over time. Patients who develop new autoantibodies  during pregnancy have a more guarded prognosis.


Conclusion


Failure  of maternal response to the fetal allograft, as well as the production  of autoantibodies, can result in repetitive pregnancy loss. Contrary to  popular belief, miscarriage is not a benign process, as the patient may  develop autoantibodies. Fortunately, these problems are easily  identified and amenable to treatment. Miscarriage due to immune  dysfunction is largely preventable today, and couples desiring  parenthood should be given appropriate consideration and evaluation.


About William L. Matzner, M.D., PhD, FACP
 

 Dr.  William Matzner works in the area of healthcare economics consulting at  Healthcare Analytics, LLC, in California. He graduated Phi Beta Kappa  from Stanford University. He received his M.D. with Honors from Baylor  College of Medicine. In 1988, he was the Solomon Scholar for Resident  Research at Cedar Sinai Medical Center. Dr. Matzner subsequently was  awarded a PhD in Neuro Economics from Claremont Graduate University. He  is board certified in Internal Medicine and Palliative Medicine. He has  researched and published extensively on the issue of reproduction and  immunology in medical literature. He has been in private practice since  1989, specializing in Reproductive Immunology and Internal medicine.
 

 Website: https://drwilliammatzner.com
 Consulting Website: https://healthcareanalytics.biz
 LinkedIn: https://www.linkedin.com/in/william-matzner-md-phd-mba-60219730
 Blog: https://drwilliammatzner.blogspot.com
 News: https://hype.news/dr-william-matzner/
 News: https://hippocratesguild.com/dr-william-matzner
 News: https://medicogazette.com/dr-william-matzner
 

Dr. William Matzner, Simi Valley, CA

Dr. William Matzner, Simi Valley, CA

Beta 2-Glycoprotein and Antiphospholipid Antibodies

Correlation In Patients With Reproductive Failure

This  is an excerpt of an article originally published in American Journal of Reproductive Immunology and was co-authored by Dr. William Matzner.  The full article is available here.


INTRODUCTION


Antibodies to negatively charged phospholipids in sera of women with immune mediated reproductive failure are believed important etiologic factors. Initial studies focused on the presence of antibodies to cardiolipin which had been shown to cause clotting abnormalities in some patients with Systemic Lupus Erythematosus (SLE), and in subset of women who suffer recurrent miscarriage. Miscarriage is believed due to thrombotic event; anticardiolipin antibodies (aCL) can cause platelet membrane and endothelial wall damage, interfere with protein C (natural anticoagulant) activation, and inhibit prostacyclins. Cardiolipin is found primarily within the inner mitochondrial membrane, unlike the other phospholipids which are found on the cell surface. Among patients with recurrent miscarriages or failed IVF, the majority of APA is directed to epitopes other that cardiolipin (approximately 90%).


Antibodies to various phospholipid epitopes have been best characterized by solid phase enzyme linked immunosorbent assay (ELISA); phospholipid is coated onto a polystyrene plate, and the antibody detected by binding to phospholipid forming a “sandwich” with a color marker which is quantified. Binding proteins are necessary for APA detection as evidenced by the perceived absence of APA when newborn or fetal calf serum are withheld from the assay. Beta 2 glycoprotein (beta 2 GP) is the specific protein involved in the binding of aCL to solid phase cardiolipin. Hypothetical mechanisms include; a) the aCL recognizes a cardiolipin beta 2 GP complex, b) the beta 2 GP is the target for aCL (not the phospholipid) and c) the actual epitope is part of the native structure of beta 2 GP. The dependence of antibodies to beta 2 GP may be disease specific. One study has shown that patients with SLE who manufacture aCL actually had antibodies against the beta 2 GP component. In another study a positive correlation between aCL and anti beta 2 GP in SLE was identified, but not between aCL and beta 2 GP in patients with end stage renal disease.


To further complicate diagnosis, false positive aCL to epitopes such as syphilis, dsDNA and others are not uncommon. Corroborating evidence for confusion include studies which show a correlation between lupus anticoagulant activity of aCL and the presence of beta 2 GP versus the absence of correlation between beta 2 GP and aCL levels in SLE. Another recent study claims a significant correlation between previous thrombosis and beta 2 GP, but not between fetal losses and a beta 2 GP. Patients with APA likely represent a heterogeneous group with antibodies directed to either the phospholipid and/or phospholipid binding proteins.


We examine the potential correlation of antibodies to beta 2 GP with that of several negatively charged phospholipids in patients who have been unsuccessful with in vitro fertilization.


STUDY GROUP


One hundred twenty three (123) consecutive patients, all under 40 years of age, with a history of reproductive failure as demonstrated by one or more failed IVFs. None of the patients had male factor as an etiology for their infertility, nor an overt history of thromboembolic disorders. These women did not have a history of recurrent pregnancy loss.


APA ELISA


Patient sera were tested for antibodies to two isotypes (IgG, IgM) of six different phospholipids (cardiolipin, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol, and phosphatidic acid) by solid phase ELISA as previously described in detail.


BETA 2 GLYCOPROTEIN ELISA


All patient sera were tested for beta 2 GP by a solid phase ELISA to IgG and IgM isotypes, as supplied by INOVA DIAGNOSITICS (San Diego , CA).


RESULTS


Of the 123 women that were tested, 33/123 had one or more positive IgG antibodies to phospholipids, of which 9/ 33 were to cardiolipin. However, only 1/123 had IgG antibodies to beta 2 GP and she was APA negative. Thirty eight of one hundred twenty three (38/123) women had one or more IgM antibodies to phospholipids, with 0/123 directed to cardiolipin IgM. In contrast, only 8/123 had IgM antibodies to beta 2 GP. Five of the eight (5/8) patients had IgM APA; 4/5 had IgM antibodies to PE and one to PI.


DISCUSSION


Our study revealed no correlation between APA and Beta 2 GP antibodies. The Beta 2 GP antibody prevalence was about 7% (9/123) with 4 associated with PE IgM and 1 with PI IgM, and 4 Beta 2 GP antibodies (1-IgG, 3 IgM) without any APA.


Unlike some of our predecessors, we were unable to identify a correlation between aCL and Beta 2 GP antibodies. Teixido, et. al., observed something similar. It is possible that in the population we studied, there maybe a relationship with oxidized low density lipoproteins as other have reported.


This study shows once again, that women unsuccessful with IVF have significant APA positivity, and that the incidence of aCL is low. There is no correlation between beta 2 GP antibody and APA status in this population. Therefore, beta 2 GP antibody in not clinically beneficial to detect phospholipid related autoimmune abnormalities in IVF failure patients.


About William L. Matzner, M.D., PhD, FACP


Dr. William Matzner works in the area of healthcare economics consulting at Healthcare Analytics, LLC, in California. He graduated Phi Beta Kappa from Stanford University. He received his M.D. with Honors from Baylor College of Medicine. In 1988, he was the Solomon Scholar for Resident Research at Cedar Sinai Medical Center. Dr. Matzner subsequently was awarded a PhD in Neuro Economics from Claremont Graduate University. He is board certified in Internal Medicine and Palliative Medicine. He has researched and published extensively on the issue of reproduction and immunology in medical literature. He has been in private practice since 1989, specializing in Reproductive Immunology and Internal medicine.


Website: https://drwilliammatzner.com

Consulting Website: https://healthcareanalytics.biz

LinkedIn: https://www.linkedin.com/in/william-matzner-md-phd-mba-60219730

Blog: https://drwilliammatzner.blogspot.com

News: https://hype.news/dr-william-matzner/

News: https://hippocratesguild.com/dr-william-matzner

News: https://medicogazette.com/dr-william-matzner

Dr. William Matzner, Simi Valley, CA

Dr. William Matzner, Simi Valley, CA

Comparison of Flow Cytometry and Microcytotoxicity

For the Evaluation of Alloimmune Therapy in Patients With Recurrent Spontaneous Abortions

This  is an excerpt of an article originally published in American journal of  Reproductive Immunology and was co-authored by Dr. William Matzner.  The full article is available here.


INTRODUCTION


The fetus is an allograft to which the mother must remain immunologically tolerant in order for the fetus to survive. Much interest has been focused on the immunology of recurrent spontaneous abortion (RSA). Up to 50% of RSA may be mediated by the immune system via inadequate maternal anti-paternal antibodies (which protect the fetus from the mother's immune system) or the presence of autoantibodies-e.g., antiphospholipid and antinuclear. These are the basis for immunotherapy with paternal leukocyte immunization (PLI), which has a reported success rate of 70% to 89% when performed and monitored properly.


There is confusion regarding the choice of laboratory test that should be performed to determine levels of maternal anti-paternal leukocyte antibodies (MAPLA). The methodology employed may have a large impact upon the selection criteria and adequacy of response to treatment. It is likely that the variations in methods used to determine MAPLA has accounted for the differences in success rate in various studies. The most popular methodologies employed include: 1) microcytotoxicity (MCX), 2) mixed lymphocyte culture (MLC), and 3) cell flow cytometry crossmatch (FCXM). Each measures slightly different responses-e.g., MCX measures only antibodies that fix complement, whereas FCXM measures both complement and non-complement fixing antibodies. FCXM has been shown to correlate well with the more difficult MLC assay although the former proves the more sensitive study. Several studies have used either FCXM or MCX to measure MAPLA. This work compares the MCX assay with FCXM.


Patient Population


The study group consisted of ten women who had a history of three or more spontaneous abortions (SABs). All ten had very low levels (<10%) of MAPLA as measured by FCXM, and all were negative for antibodies as measured by MCX. Following PLI all subjects demonstrated elevated levels (>50%) of MAPLA by FCXM.


RESULTS


Prior to therapy, all 10 patients tested negative for MAPLA as measured both by MCX and by FCXM. Following PLI all subjects demonstrated elevated levels (>50%) of MAPLA by FCXM. The 10 subjects became pregnant within 2 months of a positive MAPLA level, as measured by FCXM. At 12 weeks gestation, sera were simultaneously measured for MAPLA by MCX and FCXM. While all ten patients had very high levels of MAPLA to paternal B cells and paternal T cells by FCXM during pregnancy, only five of ten had antibodies to HLA Class I and two of ten had antibodies to HLA Class II paternal antigens by MCX. There was a large variance in the variety of antibodies to paternal HLA, as some women had antibodies to only two of the father's HLA, whereas other women had antibodies to as many as seven.


CONCLUSIONS


At first glance, there is a large discrepancy between the results of MAPLA as measured by MCX versus FCXM.


These results, however, are not surprising in an immunologic sense. Other workers have shown that the majority of antibodies found in the placenta are of the asymmetric, non-complement fixing variety. In a model similar to paternal leukocyte immunization, MacLeod et al. reported the appearance of non-cytotoxic antibodies in transfused patients that reacted with the Fc receptors of B lymphocytes.


Based on this preliminary study, the MCX assay is neither sensitive or reliable enough to determine the need and/or to monitor the effectiveness of PLI. Flow cytometry should be the modality of choice when determining the need for alloimmunotherapy and to monitor the effectiveness of treatment.


About William L. Matzner, M.D., PhD, FACP


Dr. William Matzner works in the area of healthcare economics consulting at Healthcare Analytics, LLC, in California. He graduated Phi Beta Kappa from Stanford University. He received his M.D. with Honors from Baylor College of Medicine. In 1988, he was the Solomon Scholar for Resident Research at Cedar Sinai Medical Center. Dr. Matzner subsequently was awarded a PhD in Neuro Economics from Claremont Graduate University. He is board certified in Internal Medicine and Palliative Medicine. He has researched and published extensively on the issue of reproduction and immunology in medical literature. He has been in private practice since 1989, specializing in Reproductive Immunology and Internal medicine.


Website: https://drwilliammatzner.com 

Consulting Website: https://healthcareanalytics.biz

LinkedIn: https://www.linkedin.com/in/william-matzner-md-phd-mba-60219730

Blog: https://drwilliammatzner.blogspot.com

News: https://hype.news/dr-william-matzner/

News: https://hippocratesguild.com/dr-william-matzner

News: https://medicogazette.com/dr-william-matzner

Dr. William Matzner, Simi Valley, CA.  Co-author of original article

Dr. William Matzner, Simi Valley, CA. Co-author of original article

Miscarriages and Immunotherapy

Overview by Dr. William Matzner

Some patients are uncomfortable about taking  any medication during pregnancy. Rest assured that a competent medical  professional will decide all medication and doses after giving it  thorough consideration to minimize any drug related side effects.


As  your pregnancy progresses your blood test results may change,  justifying a modification in your medication regime. If changes are  indicated, your medical provider should communicate the changes to you  immediately.
If at any time you have questions regarding medications  or suspect that you are having an allergic reaction or side effect,  please discuss them with your caregiver right away.


Aspirin 


Aspirin  is an antiinflammatory and antiplatelet agent. Should you require low  dose aspirin, the recommendation is 80 mg per day, which is equivalent  to a baby aspirin.


Aspirin, like all medication, can cause allergic  reactions. Manifestations of aspirin allergy may include dermatitis,  rhinitis, bronchospasm and even anaphylaxis. People who have a history  of asthma and nasal polyps are at increased risk for allergic reactions.


Side  effects of low dose aspirin are infrequent but can include nausea,  reflux esophagitis, abdominal discomfort, anorexia and gastrointestinal  and urinary tract bleeding. Use of high dose aspirin during pregnancy  may affect maternal and neonatal blood clotting mechanisms, leading to  an increased risk of bleed. High dose aspirin may also impair maternal  kidney function and has been causally related to increased perinatal  mortality, intrauterine growth retardation and congenital defects.  Aspirin at low doses has not been associated with these risks.


Aspirin  is excreted into breast milk in low concentration ranging from 1.1 to  10 mcg/ml. Adverse effects of platelet function in the nursing infants  have not been reported, but are a potential risk. If you choose to  breast feed your baby you should not take aspirin at that time. 


Routine  laboratory testing while on aspirin should include complete blood  count, chemistries, APTT and antiphospholipid antibody panel.


Heparin 


Heparin,  an anticoagulant, is a purifies preparation derived from animal tissue.  It is delivered as a subcutaneous injection and a typical dose would be  5000 IU twice a day.


Allergic reactions may include chills,  fever, dermatitis, asthma and anaphylactic shock. Before a therapeutic  dose is administered, a trial of 1000 IU would be prudent. Fortunately,  allergy to heparin is rare.Because of heparin's blood "thinning"  property the user is more susceptible to bleeding (skin, nose,  gastrointestinal tract, bladder, etc.). Almost all patients experience  some bruising at the site where heparin is injected.


Long term  heparin therapy has been associated with osteoporosis and spontaneous  fractures in patients who have received in excess of 15,000 units per  day for more than six months. One study of 117 patients on long term  heparin (up to 15 years) report no spontaneous fracture when subjects  received less that 10,000 units per day. Although our protocol utilizes  low dose heparinization, supplementation (dietary) with calcium is  recommended. Exercise and sun tanning may also prevent osteoporosis.


Heparin  has not been related to congenital defects, nor does it cross the  placenta. Heparin use during pregnancy has been associated with a 13 to  22% unfavorable pregnancy outcome including premature and still birth.  Please note that the study group consisted of women who had severe  maternal disease necessitating high dose anticoagulant therapy. Although  heparin is the preferred anticoagulant during pregnancy it is not risk  free. 


Heparin is not excreted in breast milk.


Relative  contraindications to the use of heparin are active bleeding, hemophilia,  thrombocytopenia or other blood dyscrasia, endocarditis or  tuberculosis. Caution should be exercised when there is underlying  hypertension and liver kidney disease. 


Routine platelet, hematocrit, APTT and antiphospholipid antibody panel monitoring during heparinization is recommended.


Prednisone 


Prednisone  is a corticosteroid. If indicated, you will be asked to take 5 or 10 mg  orally twice a day upon confirmation of pregnancy (patients with immune  mediated infertility may be on a different schedule). Drug dosage may  be adjusted depending upon follow-up blood tests.


Allergy to  prednisone is rare, as the human body manufactures a similar compound.  In fact prednisone is used to treat moderate to life threatening  allergies.


Possible adverse reaction to moderate and high  doses of prednisone include fluid and electrolyte imbalance; metabolic  disturbances e.g. hyperglycemia or gestational diabetes and  osteoporosis; susceptibility to infection; peptic ulcer; behavioral  changes e.g. nervousness, insomnia, irritability and mood swings;  myopathy; and cataracts.


Prednisone should be used with  caution in people with hypertension, congestive heart failure, diabetes  mellitus, osteoporosis, ulcerative colitis, ocular herpes and others  (please consult with doctor if you have any chronic illness).  Osteoporosis can be retarded with calcium supplementation and exercise.


Rapid  withdrawal of prednisone may cause fatigue, myalgias, arthralgias,  dizziness, hypotension, hypoglycemia and dyspnea. If you experience  these symptoms, please contact your doctor.


There are a number  of studies that review the use of prednisone during pregnancy and  effects on the fetus. The fetus appears to be protected by at least  three mechanisms: 1) enzymes in the placenta degrade the drug to an  inactive form, 2) prednisone in maternal circulation is bound to a large  protein making it harder to cross the placenta and 3) fetal liver is  not able to activate prednisone until the end of the second trimester.


Trace  amounts of prednisone have been measured in breast milk. Although these  quantities are of doubtful clinical significance, your baby's  pediatrician should be notified.


Laboratory studies to monitor  while on prednisone include complete blood count, chemistries,  electrolytes and antinuclear antibody panel.


Immunoglobulin G Infusion 


Immunoglobulin  G is a preparation of human derived antibodies. In some patients,  conventional immunotherapy with aspirin, heparin and paternal white cell  immunization may have to be supplemented with this medication. Patients  at risk for developing intrauterine growth retardation,  oligohydramnios, toxemia, or severe side effects of steroids, or have  preexisting maternal disease are prime candidates. If you require this  treatment, it is given intravenously three consecutive days monthly  during pregnancy.


Immunoglobulin G is contraindicated in  patients who are known to have had anaphylactic or severe systemic  reaction to human immune globulin. Patients with IgA deficiency should  not receive this product.


Side effects to immunoglobulin G  include fever, chills, headache, nausea, malaise and back pain. Mild  erythema following infiltration at the sire of infusion has been  reported.


Laboratory tests that need to be followed while on this treatment are quantitative immunoglobulins and immunophenotype.


Paternal Leukocyte Immunization 


Paternal  leukocyte immunization (PLI), a purified preparation of husband's white  blood cell, is administered intradermally. Because this is a blood  product, the recipient (wife) risks acquiring infectious diseases that  donor (husband) may harbor. Rh sensitization is also possible; however,  extensive steps are taken to prevent this.


Most women will  experience redness and itching at the site of immunization. Please  notify your doctor if you have any unexpected or serious reaction.


Maternal  antipaternal leukocyte antibodies (blocking antibodies), by flow  cytometry, should be followed to monitor efficacy of treatment.


***About William L. Matzner, M.D., PhD, FACP 


Dr.  William Matzner works in the area of healthcare economics consulting at  Healthcare Analytics, LLC, in California. He graduated Phi Beta Kappa  from Stanford University. He received his M.D. with Honors from Baylor  College of Medicine. In 1988, he was the Solomon Scholar for Resident  Research at Cedar Sinai Medical Center. Dr. Matzner subsequently was  awarded a PhD in Neuro Economics from Claremont Graduate University. He  is board certified in Internal Medicine and Palliative Medicine. He has  researched and published extensively on the issue of reproduction and  immunology in medical literature. He has been in private practice since  1989, specializing in Reproductive Immunology and Internal medicine.


Website: https://drwilliammatzner.com
Consulting Website: https://healthcareanalytics.biz
LinkedIn: https://www.linkedin.com/in/william-matzner-md-phd-mba-60219730
Blog: https://drwilliammatzner.blogspot.com
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William Matzner, MD.  Expert on reproductive health

William Matzner, MD. Expert on reproductive health

Miscarriages can be prevented

Overview by Dr. William Matzner

An unexpected miscarriage can shatter dreams.  Two more can be devastating. But now there is hope, and a solution. One  in every 200 couples are too genetically similar to achieve successful  pregnancy. And usually, they don't know it. That's why early detection  is vital. Without intervention, the painful pattern of miscarriage  occurs again and again.


Introduction 


One  in two hundred couples will experience two or more consecutive  miscarriages. There are five reasons for miscarriage which have been  identified: (1) Infection; (2) Anatomy abnormal; (3) Progesterone level  low; (4) Chromosome abnormal; (5) Immune mechanisms. There may also be  unknown or undiagnosed reasons and some women have multiple reasons for  miscarriages. Your obstetrician will test for most other causes of  pregnancy loss.


Immune Systems 


Advances  in immunology, the study of the body's defense systems, enable us to  understand how during pregnancy, the mother's immune system is altered  so that the fetus is not rejected by her body and allows the fetus to  grow.


The immune system is comprised of white blood cells, also  known as leukocytes, which make a variety of antibodies . Some of the  antibodies protect us and others are harmful to our bodies. Some of the  antibodies that are important to the reproductive system are: Blocking  (protective) antibodies, Antiphospholipid antibodies, and Antinuclear  antibodies.


When the immune system is the cause of miscarriage,  the chances of mother having a successful pregnancy without treatment  after 3 miscarriages is 30%, after 4 miscarriages 25%, and after 5  miscarriages 5%. With proper treatment, overall success is 80%!


Blocking Antibodies 


Early  in pregnancy, the mother's immune system receives signals from the tiny  fetus. Many of the signals are hormonal, but others come directly from  genetic messages that the father has contributed. Some of the messages  involve the tissue type, also known as the human leukocyte antigens  (HLA) are the white blood cell (leukocyte) type. HLA are expressed on  white blood cells. They are unique to each individual and allow the body  to identify anything foreign to it such as infections, cancers,  transplanted organs and fetuses. One half of the fetus's HLA type is  contributed by mother and the other half by father. When a woman becomes  pregnant, her body's immune system usually recognizes the father's HLA  as different from her own, and the white blood cells in her uterus  produce protective, blocking antibodies. These antibodies coat the  baby's cells and protect the fetus from mother's killer cells (figure 1).


If  father's HLA is too similar to mother's, her cells may not recognize  differences that are vital to the production of blocking antibodies.


Women  who have successful pregnancies and have no history of miscarriages  normally, have high levels of blocking antibodies even in the non  pregnant state vs women who miscarry and whose levels tend to be low  even when pregnant.
Through HLA tissue typing we can identify couples  who look too much "alike" In addition we can measure the ability of a  couple's cells to respond to each other i.e. level of blocking  antibodies, using sophisticated equipment which combine computers and  laser (cell flow cytometry).


Treatment involves immunizing mother  with concentrates of father's white blood cells so that the HLA signal  is amplified. When blocking levels are elevated, prior to conception,  the rate of successful term pregnancy is approximately 80%.


The  risk associated with white blood cell immunization is the possible  transmission of infectious agents that the father's blood may be  harboring. This can be avoided by testing his blood for any significant  infections. Very uncommonly, there can be a local skin infection caused  by bacteria on mother's own skin. This is easily treated.


Antiphospholipid Antibodies 


Phospholipid  molecules are normal components of all cell membranes. Some also have  glue like properties and allow cells to fuse (as you will see later).  Antibodies to phospholipid molecules can, therefore, cause problems.  Specifically, they can damage the inside of the blood vessel wall. This  allows blood cells to stick to the site f the injury and cause blood  clots (figure 3 & 4).


Some  phospholipid molecules have adhesion properties i.e. glue like, and  allow cells to fuse. The formation of the normal placenta involves the  fusion of small cells called cytotrophoblasts into giant cells known as  syncytiotro-phoblasts. The syncytiotrophoblasts play a key role in the  regulation of nutrients going to the baby.


With each pregnancy loss, there is a 10% chance that the mother will develop an antibody to a phospholipid molecule (figure 2).


Most  women with antiphospholipid antibodies are not sick. However, some have  underlying autoimmune tendencies and should be appropriately evaluated.  Women with underlying autoimmune diseases may have antiphospholipid  antibodies even before they ever become pregnant.


The treatment  for antiphospholipid antibodies involves the use of low dose (baby)  aspirin and a blood thinner called Heparin. Heparin is a very large  molecule and is unable to cross the placenta. Aspirin is able to cross  the placenta but the dose used is so small that the fetus is unaffected.  The effectiveness of treatment is mush greater when the medication, if  indicated, is started prior to conception and continued throughout the  pregnancy. All medication, if indicated should be discussed with one's  physician.


Antinuclear Antibodies 


The  nucleus is the "brain" of the cell. It contains the information that  regulates the function of the cell. Some people have antibodies to  different nuclear components. What causes these antibodies to be made is  currently under investigation but there appears to be a genetic  susceptibility which may be reflected by the HLA tissue type (refer back  to the section on blocking antibodies).


The disease that we  typically associate with antinuclear antibodies is Systemic Lupus  Erythematosus (SLE). The miscarriage rate in SLE patients is much higher  than that of the general population. Although most women who suffer  recurrent miscarriages do not have clinical signs of SLE, many exhibit  autoimmune phenomena which is similar to that seen in SLE patients. The  placentas in these women are inflamed and weakened.


The treatment  for this problem is Prednisone, a corticosteroid, which suppresses the  inflammatory process and stabilizes the cell. Prednisone does not pass  through the placenta easily and is also broken down by enzymes in the  placenta so that the fetus is exposed to only trace amounts.  Additionally, the body produces the equivalent of 8 mg per day of this  corticosteroid. When indicated, Prednisone should be started prior to  conception.


As the body is dynamic, antibody levels may change  over time. This is illustrated in figure 5. Most people have no  antinuclear antibodies all of the time (A,B). Many women who miscarry  have borderline (C,D,E) or abnormal levels of antinuclear antibodies  (F,G) (figure 5).


Patients  who develop new autoantibodies like antinuclear and antiphospholipid  antibodies during pregnancy have a more guarded prognosis.


***About William L. Matzner, M.D., PhD, FACP

Dr.  William Matzner works in the area of healthcare economics consulting at  Healthcare Analytics, LLC, in California. He graduated Phi Beta Kappa  from Stanford University. He received his M.D. with Honors from Baylor  College of Medicine. In 1988, he was the Solomon Scholar for Resident  Research at Cedar Sinai Medical Center. Dr. Matzner subsequently was  awarded a PhD in Neuro Economics from Claremont Graduate University. He  is board certified in Internal Medicine and Palliative Medicine. He has  researched and published extensively on the issue of reproduction and  immunology in medical literature. He has been in private practice since  1989, specializing in Reproductive Immunology and Internal medicine.


Website: https://drwilliammatzner.com
Consulting Website: https://healthcareanalytics.biz
LinkedIn: https://www.linkedin.com/in/william-matzner-md-phd-mba-60219730
Blog: https://drwilliammatzner.blogspot.com
News: https://hype.news/dr-william-matzner/
News: https://hippocratesguild.com/dr-william-matzner
News: https://medicogazette.com/dr-william-matzner

Dr. William Matzner, Simi Valley, California

Dr. William Matzner, Simi Valley, California

The true cost of physician turnover at Medical Clinics

Analyzed by Dr. William Matzner, MD, PhD

There are many costs involved with recruiting and retaining medical staff. HR experts project a cost factor of 16% to 20% of the physician’s annual salary purely as replacement costs, notes Dr. William Matzner in his analysis.


Just like in any business, it is prudent for a medical clinic to retain physicians over long periods of time. Uncontrolled turnover is costly not just in real dollars, but also in staff morale, patient retention and patient satisfaction. Although medicine may be practiced universally, each clinic and office has its own way of seeing patients, documenting findings, doing and reporting labs and x-rays and after-hours coverage. Those factors are always affected negatively when a “replacement” physician is interjected into the mix.


Dr. William Matzner, MD, based in California, provides his insights in a review article. Dr. Matzner is a recognized expert in Healthcare and Neuro Economics. He has conducted extensive research in and taught Cost Effectiveness Analysis, a methodology he utilizes to evaluate and recommend corporate health and wellness programming predicated on achieving targeted and desired programming and outcomes for organizations.


There are many costs involved with recruiting and retaining medical staff. But focusing just on productivity, it takes time to train the physician in the specific logistics of the practice, and decreases in productivity while the new physician is familiarizing themselves with how the clinic is operated. Generally speaking, HR experts project a cost factor of 16% to 20% of the physician’s annual salary purely as replacement costs. Add to that number recruiter and interviewing costs, and a $200,000 internist can easily cost $65,000 to replace and onboard. 

But this is just what you might consider the direct costs. The indirect costs include, for example, staff upheaval (physicians often create close bonds with staff.) Also, a physician departure, depending on the reasons, may cause other staff to depart as well. Further, depending on the clinic patient structure, you may actually lose patients or at best, have to deal with disgruntled patients. What is the value, the cost, of these issues? More importantly, are you building them in to the cost of replacing a physician?


Moreover, and this is the elephant in the room, do you build them into the cost of retaining a physician? Recruitment and retention run hand-in-hand, but too often cost is based simply on the known directs: recruiter and relocation fees. The perspective I’ve seen too often is that other doctors will take over seeing the departing physician’s patients, so we’re not losing anything, right? Wrong.


When you build a model that measures and values ancillary staff turnover attributable to a physician departure or recruitment, that measures and values lost or unhappy patients, and then add in the recruitment and productivity costs, you will arrive at a very important number – the value of keeping physicians, of reducing turnover and possibly the understanding of the value of 

adding monies to your retention budget.


In order to retain physicians a clinic may need to offer more time off, less after-hours coverage and shorter hours. A critical analysis may prove these and other retention initiatives are less costly than turnover. Cost effectiveness analysis (CEA) is a unique and clever method for analyzing this problem. Using decision tree models, and assigning not only cost but effectiveness data to the model, it will be possible to make a more informed decision as to how to recruit physicians and what economic and non-economic incentives to offer them in order to create an actual recruitment and retention program rather than just a recruitment program.


If your objective is to provide the best decision-making for your organization and take a global view of your business, expanding your sights beyond ROI, and educating other decision-makers, Cost Effectiveness Analysis can make your organization more competitive and more profitable.

*** William Lee Matzner, MD., is a recognized expert in Healthcare and Neuro Economics. With a Ph.D. in Economics, MBA and Medical Doctor degree, Dr. William L. Matzner will provide you with expert analysis on health and wellness programming, populations health management, disease management, new program development, facility development, equipment acquisitions, and other healthcare programs, acquisitions and initiatives. For more information about cost effectiveness analysis and improved financial accountability for your organization, visit Dr. Matzner at http://healthcareanalytics.biz. Dr. Matzner is also available for speaking engagements, retreat presentations and topic specific addresses.


Consulting Website: https://healthcareanalytics.biz

LinkedIn: https://www.linkedin.com/in/william-matzner-md-phd-mba-60219730

Blog: https://drwilliammatzner.blogspot.com

News: https://hype.news/dr-william-matzner/

News: https://hippocratesguild.com/dr-william-matzner

Website: https://drwilliammatzner.com     

William Lee Matzner, MD., is a recognized expert in Healthcare and Neuro Economics.

William Lee Matzner, MD., is a recognized expert in Healthcare and Neuro Economics.

Starting At Age X, You Should Get a Colonoscopy

By William L. Matzner, M.D., PhD, FACP

The importance of colon health cannot be emphasized enough. A healthy colon and regular bowel movement is not only imperative for the elimination of waste from the body, but the health of the bowel and the digestive tract is a strong indicator of your overall health.


Despite all of this, however, it’s unfortunate that colon health is neither talked about, nor given the amount of importance that it truly deserves. Even in cases when people notice changes with their bowel habits, the possibility of problems of the colon, bowel, or digestive tract are just shot down to prevent tests and screenings. 


Needless to say, this is an extremely dangerous approach and can be the reason why you’re left in the dark regarding serious colon issues for longer than you should have been. 


Unless you get checked for colon problems, there’s really no way that you’ll be able to find out whether you’re suffering from any problems or issues in your digestive tract until it’s too late. Moreover, since your gut health is related to a number of different aspects of your overall health, getting a colonoscopy done regularly is essential to ensure that you’re in the clear. 


Interested in learning more about colonoscopies, how they work, and when you should start seeing your doctor regularly for colonoscopies? 


Read on to find out everything you need to know about colonoscopies, the procedure, and how to prepare for your first colonoscopy. 


What is a colonoscopy?


The major reason why most people opt out of getting regular colonoscopies is the fact that they do not know enough about the procedure. While it’s normal to be slightly intimidated if your doctor recommends a colonoscopy, it’s important to note that the procedure itself is far from terrible. In fact, there’s a high chance that you’ll be sedated and won’t even remember the procedure. 


In a colonoscopy, your large intestine will be examined by a doctor to look for any abnormalities or causes of bleeding or pain in the abdomen, or changes in bowel habits. Through a colonoscopy, it will also be possible for your doctor to check for polyps and cancerous masses that can and should be treated before they are given the chance to aggravate. 


Since colon cancer is a common problem among adults and senior citizens, it is imperative to get a colonoscopy once every few years to ensure that your digestive tract is in perfect health and that there aren’t any problems with you and your organs. 


What do I need to know before a colonoscopy?


While colonoscopies are generally extremely safe procedures, it’s important to note that your medication might have to be adjusted if you already have some conditions, illnesses, or diseases. That’s exactly why you should let your doctor know beforehand if you’re suffering from lung problems or heart conditions, or if you have any allergies. 


Additionally, it is also important for you to let your doctor know if you’re pregnant or have diabetes since the doctor will have to provide you with a different type of medication to prevent blood clotting problems. 


What must I do before a colonoscopy?


It is extremely important for you to have a clean colon before the doctor performs your colonoscopy. That’s why your doctor may ask you to fast from all solid foods at least 24 hours before your colonoscopy. Clear liquids such as broth, water, and sports drinks are generally allowed to prevent dehydration and weakness. 


You might also be provided with a laxative that can help you empty out your bowel completely. You might be requested to consume the laxative the night before your colonoscopy is scheduled to ensure that your bowel is completely empty when the doctor is performing the procedure. In some cases, patients might also be told to consume the laxative on the morning of the procedure or examination. 


Regardless of the time that your doctor asks you to consume the laxative, it is extremely important for you to follow their instructions to the T to prevent any problems or complications during the actual procedure. 


Since you will be sedated for the colonoscopy, it is also recommended that you bring someone along who can drive you back home since the effects of the sedative are bound to last for up to 8 hours after the examination. 


How are colonoscopies performed?


Your doctor or medical professional will ask you to lie down on your left side and provide you with IV sedatives. Once you are unconscious, the doctor will insert a long device called a colonoscope into your rectum. 


Colonoscopes have a light and camera attached to allow the doctor or medical professional to get a clear view of the colon to assess whether or not everything is normal. 


The doctor might also inflate your colon to help get a better view of the colon in its entirety. 


Should the doctor find any polyps or irregular masses, a snare in the colonoscope can also be used to remove them efficiently and effectively during the colonoscopy procedure. The entire colonoscopy should not last more than half an hour should everything be normal. 


When should I start getting colonoscopies? 


While it is important for both males and females to get colonoscopies once every few years starting at age 50, there are certain factors that might want you to start investing in colonoscopies even earlier than that. In case you have one or multiple relatives who have suffered from colon problems or colon cancer, it is important to start getting colonoscopies once every 5 to 10 years starting at age 40 to ensure that you don’t have any undetected problems down the road. 


Moreover, if any relative of yours has experienced problems with their colon at an early age, you should preferably start getting tested around the age when your relative was diagnosed to prevent problems. Since a colonoscopy can help you get a clear picture of your colon health, it is not necessary for you to get the procedure done more than once every 5 to 10 years.

 

About William L. Matzner, M.D., PhD, FACP


Dr. William Matzner works in the area of healthcare economics consulting at Healthcare Analytics, LLC, in California. He graduated Phi Beta Kappa from Stanford University. He received his M.D. with Honors from Baylor College of Medicine. In 1988, he was the Solomon Scholar for Resident Research at Cedar Sinai Medical Center. Dr. Matzner subsequently was awarded a PhD in Neuro Economics from Claremont Graduate University. He is board certified in Internal Medicine and Palliative Medicine. He has researched and published extensively on the issue of reproduction and immunology in medical literature. He has been in private practice since 1989, specializing in Reproductive Immunology and Internal medicine.


Website: https://drwilliammatzner.com

Consulting Website: http://healthcareanalytics.biz

LinkedIn: https://www.linkedin.com/in/william-matzner-md-phd-mba-60219730

Blog: https://drwilliammatzner.blogspot.com

News: https://hype.news/dr-william-matzner/

News: https://hippocratesguild.com/dr-william-matzner

News: https://medicogazette.com/dr-william-matzner

Dr. William Matzner, healthcare economics consulting at Healthcare Analytics, LLC, in California

Dr. William Matzner, healthcare economics consulting at Healthcare Analytics, LLC, in California