Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04156126 |
| Other study ID # |
18-011413 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
August 23, 2019 |
| Est. completion date |
December 2024 |
Study information
| Verified date |
February 2024 |
| Source |
Mayo Clinic |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Pregnancy is a unique period which requires alterations in the immune system to allow for
tolerance of a haploidentical fetus. The goal of this study is to measure maternal blood
levels of proteins known to promote immune tolerance in early implantation and pregnancy to
look for associations between tolerance, miscarriage and failed embryo transfer. Establishing
predictive factors of miscarriage and failed in vitro fertilization could have implications
for a large portion of couples and serve to guide current and future family planning efforts.
Description:
There is increasing evidence of the importance of T cell immunoglobulin and mucin-containing
protein 3 (Tim-3) in suppressing allograft rejection, and thus it is hypothesized to play a
role in pregnancy. Galectin-9 (Gal-9) is a ligand for Tim-3 activation which promotes Th1
apoptosis signaling. Activation of Tim-3 by Gal-9 has also been shown to suppress NK cell
cytotoxicity at the maternal-fetal interface. Previous studies have evaluated Tim-3
expression on NK cells in the first trimester and found in comparison to normal pregnancies,
patients with recurrent miscarriage had decreased Tim-3 expression and less anti-inflammatory
cytokine production. In a mouse model, transfer of Tim-3 expressing NK cells reduced
miscarriage rates. During the first trimester, Gal-9 levels increase and remain elevated
throughout pregnancy. Preliminary data in a small population of patients who had miscarriages
were found to have significantly lower Gal-9 levels detected at 8 weeks gestation compared to
those who continued on to have a term pregnancy. Additionally there is evidence that Gal-9
increases production of interleukin (IL-4), and in patients with recurrent miscarriage IL-4
levels are decreased [5]. These identifications have prompted further investigation into
predictive value of Gal-9 and IL-4 levels in early pregnancy on the outcome of a pregnancy.
Angiogenic factors, such as vascular endothelial growth factors (VEGF), have been shown to
have a critical role in pregnancy at both the local and systemic level. Locally, CD56+
uterine natural killer cells within the endometrium express higher levels of VEGF in women
with recurrent miscarriage versus women with proven fertility. Histological differences in
VEGF expression and placental vascular bed patterns have been observed in tissue from
patients with a miscarriage compared to women with a viable pregnancy. Serum VEGF levels are
significantly different in patients with recurrent pregnancy loss than in women with proven
fertility [8]. Serum VEGF levels, including VEGF-A, -C, and -D, are significantly higher at 8
weeks gestation in pregnancies that result in a spontaneous loss compared to pregnancies that
go on to result in a live birth. Therefore, additional studies are needed to establish if
early first trimester serum levels of VEGFs, Gal-9, and IL-4 are significantly different in
pregnancies that result in miscarriage or live birth. Miscarriage affects approximately
15-20% of pregnancies. Therefore, establishing predictive factors of miscarriage could have
implications for a large portion of couples and could serve to guide current and future
family planning efforts. It is, essential to gain an understanding of mechanisms underlying
infertility and miscarriage, so that more effective treatments and protocols can be
developed.
The study hypothesis states low levels of Gal-9 and IL-4, and high levels of VEGF at the time
of embryo transfer will be predictive of failed embryo transfer and spontaneous miscarriage.
The primary endpoint is the maternal blood levels of galectin-9, IL-4 and VEGF-A,-C,-D on the
day of embryo transfer in cycles that result in live birth versus no live birth, or that
result in miscarriage compared to live birth.
