Please select the eligibility criteria that correspond to the clinical trial below.
Title: Pregnancy Outcomes in Women With Unexplained Recurrent Pregnancy Loss Treated With Low Dose Aspirin and Unfractionated Heparin
Brief Summary: Objective To determine maternal and fetal outcomes in women with Unexplained RPL managed with aspirin or unfractionated heparin (UFH) plus aspirin during pregnancy.

Design: prospective clinical controlled study. Setting: high-risk pregnancy unit- Benha university hospital. Methods: Pregnant women with unexplained recurrent miscarriage attending high-risk pregnancy unit. 200 selected patients with previous unexplained recurrent miscarriage are divided into 2 groups: group A (n = 100) receive low-dose aspirin (81 mg once daily orally) plus heparin (5000 IU) every 12 h with the ﬁrst positive pregnancy test while group B (n = 100) receive no thing .

Main outcome measures: Maternal outcomes included thromboembolic and haemorrhagic complications and pregnancy-induced hypertension .Prematurity, intrauterine growth restriction and neonatal death were considered as maternal and fetal complications


Options:
A: Inclusion Criteria:

* patients with unexplained recurrent pregnancy loss (RPL)

Exclusion Criteria:

* previous history of Diabetes Mellitus or thyroid dysfunction or cardiac disease
* Thrombocytopenia (\<100000/ml)
* bleeding tendencies
* ectopic pregnancy
* past history of vascular thrombosis
* uterine anomalies
* multiple gestation
B: Inclusion Criteria:

* Patients with a minimum of three consecutive pregnancy losses before 10 weeks gestation
* Positive lupus anticoagulant and/or anticardiolipin antibodies (IgG and IgM) on at least two occasions twelve weeks apart .
* Age between 19 - 37 years,
* Body mass index between 19-30

Exclusion Criteria:

* Parental chromosomal abnormalities
* Uterine abnormalities
* Luteal phase defect
* Systemic lupus erythematosus
* Previous thromboembolism
* Sensitivity to aspirin.
C: Inclusion Criteria:

Women must be at high risk for thromboembolism for one of the following reasons:

1. Known low risk thrombophilia (Known = diagnosed prior to enrollment and low risk thrombophilia includes heterozygous factor V Leiden or prothrombin gene variant or protein C deficiency or protein S deficiency. If not previously tested then assumed not to have thrombophilia).
2. Immobilization (defined as \>90% of waking hours in bed, of a week or more at any point in the antepartum period).

OR any two of the following reasons:

1. Postpartum infection (fever (temperature\>38.5oC) and clinical signs/symptoms of infection and elevated neutrophil count (higher than local lab normal))
2. Postpartum hemorrhage (Estimated blood loss \>1000 ml during delivery and postpartum)
3. Pre-pregnancy BMI \>25 kg/m2
4. Emergency cesarean birth (emergency = not planned prior to onset of labour)
5. Smoking \>5 cigarettes per day prior to pregnancy
6. Preeclampsia (blood pressure ≥ 140mmHG systolic and/or ≥90 mmHg diastolic on at least one occasion and proteinuria (1+ on urine dipstick or 300mg/dl or total excretion of 300mg/24 hours) or typical end-organ dysfunction.
7. Infant birth weight (adjusted for sex and gestational age) \<3rd percentile (i.e., small for gestational age).

Exclusion Criteria:

1. Less than 6 hours or more than 36 hours since delivery at the time of randomization
2. Need for anticoagulation as judged by the local investigator, may include but not limited to:

   1. Personal history of previous provoked or unprovoked VTE (DVT or PE)
   2. Continuation of LMWH that was started in the antenatal period for VTE prophylaxis
   3. Mechanical heart valve
   4. Known high-risk thrombophilia (Known = diagnosed prior to enrolment and high-risk thrombophilia includes deficiency of antithrombin (at least 1 abnormal lab result), persistently positive anticardiolipin antibodies (\> 30U/ml on two measurements a minimum of six weeks apart), persistently positive Anti B2 glycoprotein antibodies (\> 20U/ml on two measurements a minimum of six weeks apart), persistently positive lupus anticoagulant (positive on two measurements a minimum of six weeks apart), homozygous factor V Leiden (FVL), homozygous prothrombin gene mutation (PGM), compound heterozygosity factor V Leiden (FVL) and prothrombin gene mutations (PGM), more than 1 thrombophilia (any combination of 2 or more: FVL, PGM, protein C deficiency, protein S deficiency). If not previously tested then assumed not to have thrombophilia).
3. Contraindication to heparin therapy, including:

   1. History of heparin induced thrombocytopenia (HIT)
   2. Platelet count of less than 80,000 x 106/L on postpartum Complete Blood Count(CBC)
   3. Hemoglobin ≤ 75 g/L on postpartum CBC
   4. Active bleeding at any site (not resolved prior to randomization)
   5. Excessive postpartum vaginal bleeding (\>1 pad per hour prior to randomization).
   6. Documented gastrointestinal ulcer within 6 weeks prior to randomization
   7. History of heparin or LMWH allergy
   8. Severe postpartum hypertension (systolic blood pressure (SBP) \> 200mm/hg and/or diastolic blood pressure (DBP) \> 120mm/hg)
   9. Severe hepatic failure (INR \>1.8 if liver disease suspected)
4. Have received more than one dose of heparin or LMWH since delivery
5. \< age of legal majority in local jurisdiction (age \<18 in Canada)
6. Prior participation in PROSPER
7. Unable or refused to consent
D: Inclusion Criteria:

One or more of the following:

* Previous preeclampsia
* Previous unexplained intra-uterine growth restriction
* Previous recurrent miscarriage:

  * three(3) or more unexplained miscarriage at less than 10 weeks gestation;
  * two (2) or more unexplained fetal loss between 10 and 16 weeks gestation;
  * one (1) or more unexplained fetal loss at or greater than 16 weeks gestation
* Previous abruptio placenta
* Previous personal history of VTE:

  * Previous documented secondary proximal VTE,
  * Previous documented calf-vein thrombosis (idiopathic or secondary),
  * Previous superficial phlebitis
* First degree relative with symptomatic thrombophilia
* Pregnancy - \> 4weeks gestation and \< 20 weeks gestation
* Thrombophilia:
* Two abnormal tests, and no normal tests

  * 3.1 Protein S
  * 3.2 Protein C
  * 3.3 Antithrombin
* Two positive tests

  * 3.4 Anticardiolipin immunoglobulin M (IgM) (\>30 U/ml)
  * 3.5 Anticardiolipin immunoglobulin G (IgG) (\>30 U/ml)
  * 3.6 Anti-b2 glycoprotein IgG (\>20 U/ml)
  * 3.7 Anti-b2 glycoprotein IgM (\>20 U/ml)
  * 3.8 Lupus anticoagulant
* One positive test

  * 3.9 Factor V Leiden (heterozygous or homozygous)
  * 3.10Prothrombin gene defect (heterozygous or homozygous)

Exclusion Criteria:

* Less than 4 weeks gestation or greater than 20 weeks gestation
* No confirmed thrombophilia
* Contraindication to heparin therapy

  * History of heparin induced thrombocytopenia
  * Platelet count less than 100,000 109/L
  * History of osteoporosis or steroid use
  * Actively bleeding
  * Documented peptic ulcer within 6 weeks
  * Heparin, bisulfite or fish allergy
  * Severe hypertension (Systolic Blood Pressure \>200mmhg and/or Diastolic Blood Pressure \>120mmHg)
  * Serum creatinine greater than 80 umol/L (1.3mg/dl) and an abnormal 24 hour urine creatine clearance (\<30ml/min)
  * Severe hepatic failure (INR \>1.8)
* Geographic inaccessibility
* Need for anticoagulants, discretion of the investigator such as but not limited to:

  * Recurrent fetal loss and phospholipid antibody syndrome
  * Prior idiopathic proximal VTE:
  * History of idiopathic deep venous thrombosis (DVT) or pulmonary embolism (PE) treated with anticoagulants (\> 1 month of heparin or warfarin) or inferior vena cava (IVC) interruption;
  * Idiopathic is a VTE occurring outside all of the following periods: antepartum, postpartum, oral contraceptive use, surgery, immobilization, cast, and malignancy
  * Mechanical heart valve
* Legal lower age limitations (country specific)
* Prior participation in TIPPS
* Unable/unwilling to provide informed consent

Answer: A