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| William Matzner, MD, 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
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.
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
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.
