Recurrent Pregnancy Loss Clinical Trial
Official title:
Uterine Artery Doppler Changes After Vaginal Administration of Isosorbide Mononitrate In Patients With Unexplained Recurrent Pregnancy Loss
compare uterine artery blood flow before and after the administration of Isosorbide mononitrate as a nitric oxide donor during mid secretory phase of menstrual cycle for patients with unexplained recurrent pregnancy loss.
Recurrent pregnancy loss (RPL) is an important reproductive health issue, because it affects 2%-5% of couples. The incidence of RPL varies widely because of the differences in the definitions and criteria used, as well as the populations characteristics (El Hachem et al., 2017). The reported incidence of early pregnancy loss depends on the method used to detect pregnancy. An estimated 50% of all conceptions are lost at preclinical stages owing to biochemical loss or implantation failure, further 9-20% of clinically recognized pregnancies are miscarried, mainly during the first trimester (weeks 5-12 of gestation), studies consistently demonstrate a sharp reduction after 12 weeks of gestation to an incidence of ~1% suggesting that most pregnancy losses occur soon after implantation (Dimitriadis et al., 2020). The Royal College of Obstetricians and Gynecologists defines RPL as three or more consecutive pregnancy losses, The most recent RPL guideline from European Society of Human Reproduction and Embryology states that RPL could be considered after the loss of two or more pregnancies and stresses the importance of the need for further scientific research, including epidemiological studies on the effect of various RPL definitions on diagnosis, prognosis and treatment (ESHRE 2017). Common established causes include uterine anomalies, antiphospholipid syndrome, hormonal and metabolic disorders, and cytogenetic abnormalities. Other etiologies have been proposed but are still considered controversial, such as chronic endometritis, inherited thrombophilia, luteal phase deficiency, and high sperm DNA fragmentation levels (Yang et al., 2019). Over the years, evidence-based treatments such as surgical correction of uterine anomalies or aspirin and heparin for antiphospholipid syndrome have improved the outcomes for couples with recurrent pregnancy loss. However, almost half of the cases remain unexplained and are empirically treated using progesterone supplementation, anticoagulation, and/or immunomodulatory treatments. Regardless of the cause, the long-term prognosis of couples with recurrent pregnancy loss is good, and most eventually achieve a healthy live birth. However, multiple pregnancy losses can have a significant psychological toll on affected couples, and many efforts are being made to improve treatments and decrease the time needed to achieve a successful pregnancy (El Hachem et al., 2017). Appropriate endometrial receptivity is vital in achieving a normal pregnancy, Inadequate uterine perfusion leading to endometrial and subendometrial hypoxia could induce low endometrial receptivity, which would increase spontaneous abortion (taylor et al; 2019 & Mansour et al;2020). Other studies also suggest that uterine perfusion may regulate endometrial receptivity, and that impaired uterine perfusion is one of the causes of URPL. In recent years, Doppler ultrasound with assessments of parameters of uterine artery and endometrium have become widely accepted when evaluating endometrial receptivity(Yang et al., 2019). Nitric oxide (NO) is a gas and a free radical which is now recognized to have very important physiological roles. NO is important in the endothelium-dependent regulation of blood flow and pressure as well as inhibiting the activation of blood platelets. By this process , NO activates a haem-containing enzyme called soluble guanylyl cyclase which is activated a thousand fold to produce the signaling molecule cyclic GMP. This has many effects at the molecular level to set in train the pathways which propagate the diverse physiological actions of NO(Zhao et al., 2015). NO plays important functional roles within vascular system, it induce vasodilation ,inhibit platelet aggregation and adhesion to endothelial cells, also inhibit smooth muscle proliferation ,regulates apoptosis and maintain endothelial barrier integrity. NO is the main vasodilator agent in the placenta ,which is the interface between mother and fetus ,and this is the reason why this molecule is crucial in different physiological aspect of pregnancy ,it is involved in implantation ,platelet adhesion ,early embryonic development .Related to placental perfusion, NO seem to influence cytotrophoblastic invasion during first stage of pregnancy and to mediate the remodeling of spiral arteries ,facilitating adequate blood supply to the growing fetus (Zullino et al., 2018). ;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT04718233 -
Effect of Sildenafil Citrate on Mid Luteal Phase Uterine Artery Blood Flow in Patients With Recurrent Pregnancy Loss
|
Phase 2 | |
Recruiting |
NCT01946945 -
Comparison of Standard ART Practice vs. Trophectoderm Biopsy and Whole Chromosome Analysis
|
Phase 2 | |
Completed |
NCT02572154 -
Sperm DNA Fragmentation in Recurrent Pregnancy Loss
|
N/A | |
Completed |
NCT03174951 -
Immunomodulatory Effects of IVIg on Pregnancy Rate of Patient With Recurrent Pregnancy Loss
|
Phase 2 | |
Recruiting |
NCT05444283 -
Genomic Predictors of Recurrent Pregnancy Loss
|
||
Active, not recruiting |
NCT04621773 -
Live Birth Rate in Patients With Unexplained Recurrent Pregnancy Loss
|
||
Recruiting |
NCT02990403 -
The Novel Immunomodulatory and Anticoagulant Therapies for Recurrent Pregnancy Loss
|
Phase 4 | |
Recruiting |
NCT02990390 -
The Epidemiology of Recurrent Spontaneous Abortion Associated With Thrombophilla
|
N/A | |
Not yet recruiting |
NCT05612620 -
Elucidating the Microbiome in Patients With Recurrent Pregnancy Loss
|
||
Not yet recruiting |
NCT05520112 -
Treatment of Recurrent Pregnancy Loss Using Mesenchymal Stem Cells
|
Phase 1/Phase 2 | |
Suspended |
NCT04397042 -
SCUBE-1 and Carotid Intima Media Thickness in Recurrent Pregnancy Loss
|
||
Recruiting |
NCT06007560 -
Aerobe Cycling Training in Women With Unexplained Recurrent Pregnancy Loss
|
N/A | |
Completed |
NCT02386384 -
TNFα and MFG-E8: Novel Biomarkers to Predict Implantation Failure
|
N/A | |
Recruiting |
NCT01635426 -
Aspirin Versus Clopidogrel Effect on Uterine Blood Flow in Women With Unexplained Recurrent Miscarriages
|
Phase 2/Phase 3 | |
Suspended |
NCT01546350 -
Preimplantation Genetic Diagnosis Using Blastocyst Biopsy and Array CGH
|
Phase 2 | |
Completed |
NCT00721591 -
Pharmacokinetics of Low Molecular Weight and Unfractionated Heparin in Pregnancy
|
N/A | |
Terminated |
NCT00564174 -
Low Molecular Weight Heparin and Aspirin in the Treatment of Recurrent Pregnancy Loss: A RCT
|
N/A | |
Completed |
NCT04455256 -
Evaluation of Endoplasmic Reticulum Stress in Patients With Recurrent Pregnancy Loss
|
||
Not yet recruiting |
NCT05237843 -
Hydroxychloroquine in Unexplained Recurrent Pregnancy Loss
|
Phase 1 | |
Recruiting |
NCT02144064 -
Pregnancy Outcomes in Women With Unexplained Recurrent Pregnancy Loss Treated With Low Dose Aspirin and Unfractionated Heparin
|
Phase 3 |