Pregnancy Loss, Pregnancy Loss, Early
Conditions
Keywords
progesterone, low molecular weight heparine, recurrent miscarriage, pregnancy loss
Brief summary
The objective of the trial is to assess whether the combination of enoxaparine (LMWH) with progesterone increases the live birth rate compared to standard of care (no active treatment) in women with unexplained recurrent pregnancy loss.
Interventions
Vaginal micronized progesterone 800 mg daily administered in two divided doses .
DRUGEnoxaparin (LMWH)
Administered subcutaneously once daily at a weight-adjusted prophylactic dose according to body weight or applicable local guidelines.
Sponsors
General University Hospital, Prague
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* History of ≥2 consecutive unexplained miscarriages before 20 weeks of gestation. * Confirmed intrauterine pregnancy by ultrasound and/or serum β-hCG (≥5 weeks). * Willingness to follow study procedures (progesterone use, possible daily - injections) and provide written informed consent. * No medical contraindication to progesterone or LMWH.
Exclusion criteria
* Documented antiphospholipid syndrome or any current anticoagulant requirement. * Anatomical abnormalities (e.g., significant uterine malformations, large fibroids) conclusively linked to RPL. * Known hypersensitivity to enoxaparine or heparins, or prior heparin-induced thrombocytopenia (HIT). * Use of systemic steroids (beyond standard pregnancy doses) for other immunological or inflammatory conditions. * Severe renal insufficiency (eGFR \<30 mL/min), advanced liver disease, or other clinically significant systemic autoimmune disease (e.g., systemic lupus erythematosus, rheumatoid arthritis) that may affect pregnancy or study compliance. * Inability or unwillingness to comply with study requirements (language barriers, severe psychiatric conditions, etc.). * Abnormal karyotype
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Live Birth Rate | At delivery (≥24+0 weeks of gestation) | Proportion of randomized participants who deliver at least one live-born infant at ≥24+0 weeks of gestation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ongoing Pregnancy Rate at 22 Weeks | From enrollment to the end of 22 weeks of the index pregnancy. | Proportion of randomized participants with an ongoing intrauterine pregnancy at 22+0 weeks of gestation, confirmed by ultrasound demonstrating fetal cardiac activity. |
| Maternal Complications | From enrollment to the end of treatment at 6 weeks post-labor. | Incidence of pregnancy-related complications, including preeclampsia (defined by ISSHP), gestational hypertension, gestational diabetes, placental abruption, postpartum hemorrhage (defined as estimated blood loss \>500 mL following vaginal delivery or \>1000 mL following cesarean section). |
| Neonatal Outcomes: | From enrollment to the end of treatment at 6 weeks post-labor. | Birth weight (grams), APGAR scores at 1 and 5 minutes post-delivery (APGAR at 10 minutes may be recorded if available), admission to neonatal care unit (NICU), and presence of congenital anomalies confirmed postnatally. |
| Safety of the trial medication | From enrollment to the end of treatment at 6 weeks post-labor. | Incidence of major bleeding events (overt bleeding requiring transfusion, surgical intervention, or hemodynamic intervention) and minor bleeding events (mucosal or injection-site bleeding), thrombocytopenia (defined as platelet count \<100,000/μL), hypersensivity, and injection-site reactions. |
| Adherence and Tolerability: | Treatment discontinuation: from initiation at 5-7 weeks' gestation to 36+0 weeks or delivery. Pain and missed-dose outcomes: assessed at 20 and 34 weeks' gestation and 6 weeks postpartum. | Treatment discontinuation rate and reasons for discontinuation (including adverse events); participant-reported injection-site pain associated with LMWH treatment, assessed using a numerical rating scale from 0 (no pain) to 10 (worst imaginable pain); participant-reported missed doses of study treatment and reasons for missed doses; and completeness of medication diaries. |
Countries
Czechia
Contacts
CONTACTZdeněk Laštůvka, MD, PhD
CONTACTJana Brabcová, PhD
Outcome results
None listed