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| Dr. William Matzner, Simi Valley, CA |
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
News: https://medicogazette.com/dr-william-matzner
William Matzner, MD (Simi Valley, California), has been practicing medicine since 1989, Internal Medicine and Reproductive Immunology. M.D. with Honors from Baylor College of Medicine.
