Labor induction rates are increasing worldwide, yet nulliparous patients remain at high risk of failed induction and intrapartum cesarean delivery as well as prolonged labor which are associated with increased maternal morbidity, adverse outcomes in future pregnancies, increased neonatal morbidity and negative childbirth experience. This study aims to evaluate whether macrophage activation biomarkers in cervicovaginal secretions can predict successful labor induction in low-risk nulliparous women at term with an unfavorable cervix (Bishop score <6).

The study focuses on three patented biomarkers of "imminence of delivery" (MCP1, CD14, and CD163), previously shown to be markedly elevated during spontaneous labor. We hypothesize that higher biomarker concentrations reflect biological readiness for labor and are associated with successful induction, defined as entry into the active phase of labor (cervical dilation ≥6 cm). Secondary objectives include evaluating the association between biomarker concentrations and labor progression. Identifying reliable predictive biomarkers could improve patient selection for induction and optimize obstetrical management in nulliparous women.

The aim of labor induction is to reduce maternal and/or fetal complications associated with continuation of pregnancy while enabling vaginal delivery. The practice of term labor induction is increasing both in France and worldwide. In the French national MEDIP study, the cesarean section rate among nulliparous women undergoing induction between 37 and 41 weeks of gestation was 30% (compared with 8% among multiparous women), and two-thirds of these cesarean deliveries occurred before the onset of the active phase of labor (6 cm cervical dilation), often defining failed labor induction. However, cesarean delivery during labor, compared with vaginal delivery, is associated with increased maternal morbidity and impaired obstetrical outcomes in subsequent pregnancies. Cervical examination by digital assessment, allowing calculation of the Bishop score, is currently the only tool used to predict induction success; the lower the score, the higher the risk of failed induction. Therefore, among nulliparous patients with an unfavorable Bishop score, identifying those likely to achieve vaginal delivery would be particularly useful, especially as induction is increasingly proposed to this population.

Major changes occur in the maternal and fetal immune, metabolic, and endocrine systems during the two to four weeks preceding delivery. The investigators hypothesize that, at the time of induction, some key biological changes may already have occurred, thereby facilitating the initiation and progression of labor.

Our team investigates the mechanisms of parturition, particularly to identify biomarkers associated with successful induction in the setting of an unfavorable cervix. Three macrophage activation biomarkers referred to as "imminence of delivery" biomarkers (MCP1, CD14, and CD163) have been patented by our team. Their concentrations in vaginal secretions are 10- to 20-fold higher during spontaneous labor compared with women not in labor (scheduled cesarean delivery).

We hypothesize that the concentration of these biomarkers in cervicovaginal secretions is associated with successful term induction. Our objective is to evaluate the association between the concentration of three macrophage activation biomarkers in cervicovaginal secretions (MCP1, CD14, and CD163) and successful labor induction among low-risk nulliparous women with an unfavorable cervix (Bishop score <6) at ≥39 weeks of gestation. We hypothesize that high biomarker concentrations will predict successful induction.

The primary outcome is successful induction, defined as entry into the active phase of labor (cervical dilation ≥6 cm).

Our secondary objectives are to evaluate the association between the concentration of the three macrophage activation biomarkers in cervicovaginal secretions and labor progression (duration of induction and duration of labor). High concentrations of macrophage activation biomarkers in vaginal secretions may be associated with shorter induction and labor durations. These factors have a direct impact both on obstetrical morbidity (particularly the hemorrhagic risk associated with prolonged labor) and on patients' childbirth experience (particularly their level of anxiety).

Inclusion Criteria:

• Age ≥ 18 years
• Singleton pregnancy
• Gestational age ≥ 39 weeks
• Nulliparous
• Live foetus
• Cephalic presentation
• Intact membranes
• Bishop score < 6
• Willing to participate in the study

Exclusion Criteria

• A minor or a protected adult (under guardianship or conservatorship)
• Individuals who don't speak French or are not accompanied by a third party who speaks French
• Suspected intrauterine fetal growth restriction (estimated fetal weight < 3rd percentile or < 10th percentile with abnormal fetal Doppler)
• Presence of fetal malformations and/or genetic or chromosomal abnormalities

Nulliparous patients