A Lifestyle Intervention to Improve in Vitro Fertilization Results
A Lifestyle Intervention to Improve in Vitro Fertilization Results
Embryo adhesion and placentation depend on tissue plasminogen activator (tPA)-mediated
 activation of brain-derived neurotrophic factor, vascular endothelial growth factor and other
 growth factors, formation of hemidesmosomes, and degradation of extracellular matrix and
 basement membrane, either directly or by activating matrix metalloproteinases.

 Since glucose and insulin stimulate release of a major tPA inhibitor by endothelial cells -
 plasminogen activator inhibitor (PAI)-1 - the investigators hypothesized that lifestyle
 interventions proven effective in maintaining glucose and insulin levels within the normal
 range would increase the take home baby rate in women undergoing assisted reproduction.
Tissue plasminogen activator (tPA) has a well-known role in the coagulation pathway. tPA
 converts plasminogen to plasmin. Plasmin dissolves fibrin clots, thus limiting thrombus
 formation to the site of vascular injury.

 In the extravascular compartment, tPA is a pivotal mediator of tissue formation and
 remodeling. Due to its proteolytic activity, tPA participates in processes as diverse as
 embryo adhesion, placental angiogenesis and vasculogenesis, and neuronal plasticity. Embryo
 adhesion and placentation, for example, depend on tPA-mediated activation of brain-derived
 neurotrophic factor, vascular endothelial growth factor and other growth factors, formation
 of hemidesmosomes, and degradation of extracellular matrix and basement membrane, either
 directly or by activating matrix metalloproteinases.

 Assuming low tPA activity would impair both blood clot dissolution and placentation, the
 investigators postulated that patients with consecutive first-trimester abortions would have
 a high prevalence of severe dysmenorrhea, accompanied by the passage of large clots.

 In 2011, the investigators assessed the prevalence of severe dysmenorrhea during early
 adolescence in two groups. The first one was made of women with ≥ 2 consecutive
 first-trimester abortions, and the other, of women with ≥ 2 living births, and no losses or
 preterm deliveries. Severe dysmenorrhea was defined as suprapubic menstrual cramp, intense
 enough to cause repeated absenteeism from school or fainting in the absence of analgesia.
 Early adolescents are unlikely to use contraceptives, or to have become pregnant, two
 situations that may reduce the pain. In this study, severe dysmenorrhea increased the chances
 of having consecutive first-trimester miscarriages by sevenfold (95% Confidence Interval: 3.4
 to 14.1; p<0.001).

 Since glucose and insulin stimulate release of a major tPA inhibitor by endothelial cells -
 plasminogen activator inhibitor (PAI)-1 - the investigators hypothesized that lifestyle
 interventions proven effective in maintaining glucose and insulin levels within the normal
 range would increase the take home baby rate in women undergoing assisted reproduction.

 The protocol has already been tested at a Brazilian tertiary care center in women with
 unexplained consecutive first-trimester abortions, conceiving spontaneously. The objective of
 this study was to observe the impact of lifestyle interventions on the take home baby rate,
 and to observe if the intervention could reduce the prevalence of preeclampsia and neonatal
 hypoglycemia.

 From 2011 to 2015, 480 patients aged 18 to 42 years with ≥ 2 consecutive first-trimester
 abortions documented by pathology or ultrasonography, were randomly assigned to protocol
 Walking and Diet (W+D) or to standard follow-up (controls). Women were enrolled independent
 of having had severe dysmenorrhea during adolescence. Patients assigned to protocol W+D were
 instructed to walk briskly for ≥ 40 minutes seven days a week. In addition, they were
 recommended to avoid high-carbohydrate meals such as snacks, candies, fiber-free juices,
 coconut water and sugar-sweetened beverages, and to eat two daily servings of meat, poultry,
 fish (e.g. 2 g/kg) or other protein-rich food, starting when they decided to get pregnant and
 continuing until delivery. Women with antiphospholipid antibodies, second- or third-trimester
 losses, multiple pregnancies, anatomical abnormalities that could increase the risk of
 first-trimester abortions, or any condition requiring a priori anticoagulation were excluded.
Inclusion Criteria:

 -  women undergoing assisted reproduction

 Exclusion Criteria:

 1. liver failure, kidney failure or other conditions that prevent the patient from eating
 proteins.

 2. multiple pregnancy.

 3. paraplegia, hemiplegia, arthropathy and other conditions that prevent the participant
 from exercising.

 4. participants lost to follow-up.

 5. conditions that may strongly affect pregnancy results, such as a serious accident

 6. participants assigned to non-intervention group following the recommendations given to
 intervention group.