The mapping of the human genome, along with research in gene
testing techniques, have recently revealed correlations between chromosomal
mutations and numerous problems with conception and fetal development.
Three
new gene tests in particular hold tremendous promise, and may help explain
fertility and recurrent pregnancy loss problems that continue to inexplicably
plague patients:
Miscarriage is the most common gestational disorder, affecting about 15% of all pregnancies. Cutting edge studies have suggested congenital and acquired blood clotting factors as a possible cause of recurrent pregnancy loss.
Given the convincing connection between recurrent pregnancy loss, cardiovascular health and blood clotting, it is prudent to recommend this evaluation, even in lieu of symptoms.
Thrombophilia can be a congenital disorder, or induced through surgery, obesity, pregnancy, oral contraceptive use, antiphospholipid syndrome, and extended periods of immobility.
· Early and late recurrent pregnancy loss may be caused by thrombophilia, as likely induced by uteroplacental microvascular thrombosis and hypoperfusion.
· Clotting may also cause intrauterine growth retardation, placental abruption or placental infarction.
·
Pre-eclampsia and pregnancy induced hypertension have also been related to
abnormal placental vasculature, in addition to neural tube defects and a
disturbance of hemostasis brought on by abnormal clotting factors.
Geneticists have identified ten thrombophilic mutations associated with
pregnancy related disorders. In fact, recent studies reveal that patients who
experience recurrent miscarriage often have one or more of these thrombophilic
markers. Clotting problems associated with insulin resistance may cause
abnormal uterine blood flow, suggesting a connection between polycystic
ovarian syndrome (PCOS) and thrombophilia.
Thrombophilia Gene evaluation will test by DNA probes and gel
electrophoresis for the presence of:
o Factor V
o Factor V Y1702C
o Factor V G1691A (Leiden)
o Factor V H1299R (R2)
o Factor XIII V34L
o MTHFR
o C677T
o A1298C
o Prothrombin G20210A
o β-Fibrinogen -455 G>A
o
PAI-1 4G/5G
HPA1 a/b (PLA1/PLA2)
A buccal swab sample, taken by the
patient and mailed to our laboratory for analysis with a $400 deposit is all
that’s needed. Note: Patient’s insurance company will be billed, and once
payment is received, the deposit will be reimbursed.
Miscarriage is the most common gestational disorder, affecting about 15% of all pregnancies. Although the majority of sporadic losses and a lesser proportion of recurrent pregnancy losses have been shown to be due to chromosomal abnormalities in the fetus, a significant proportion of such losses has remained unexplained.
Thankfully, an answer may be found in a mutation of the so-called “HLA-G” gene of the mother, and may explain recurrent pregnancy loss cases.
In 1990 researchers discovered that the HLA gene somehow regulated fetal placental cells at the maternal-fetal interface. The HLA gene translated proteins have been shown to:
o Inhibit maternal T cell proliferation
o Induce IL-10 production in placental trophoblast cells and peripheral blood monocytes
o Regulate chorionic angiogenesis
This single gene consequently encodes multiple isoforms that fulfill a variety of functions, presumably to ensure the survival of the allogeneic fetus. A mutation in HLA-G can interfere with this vital process, resulting in recurrent pregnancy losses. At least four different mutations have been identified to date.
HLA-G will test by DNA sequencing for the presence of:
o The 0105N mutation is a deletion of nucleotide 1597 (C)/amino acid 130
o The -725C/G promoter polymorphis
Fetal loss rates are higher when even only one parent carries the -725G allele
A buccal swab sample, taken by the patient and mailed to our laboratory for analysis with a $450 deposit is all that’s needed.
Note: Patient’s insurance company will be billed, and once payment is received, the deposit will be reimbursed.
Few things can prove more frustrating (and less productive) than the inability to explain infertility. Since this “diagnosis by exclusion” dilemma plagues as many as 10 to 15% of couples seeking fertility treatment, the determination of sound etiology is eminently worthwhile.
Thankfully, an answer may be found in a mutation of the so-called “progesterone receptor” allele, and may explain inexplicable fertility problems in some instances.
Under normal circumstances, progesterone receptor activity is down regulated in endometrial epithelium during a time when embryo implantation (luteal phase) takes place. Any mutation in the receptor may interfere with this normal down-regulation, disrupting implantation.
Infertility may be caused by abnormally increased
receptor stability and transcriptional activity due to the mutant allele. At
least three different mutations have been identified to date. Experimental in nature, this test is
more suited to investigation than as a routine tool for definitive clinical
diagnosis.
Progesterone receptor allele will test for the presence of:
o Alu insertion at intron G.
o G to T point mutation in first nucleotide of codon 660 within exon 4, resulting in a valine to leucine substitution
o
C to T point mutation in third nucleotide of codon 770 within exon 5 (silent
A buccal swab sample, taken by the patient and mailed to our laboratory for
analysis with a $450 deposit is all that’s needed. Note: Patient’s
insurance company will be billed, and once payment is received, the deposit
will be reimbursed.