Pregnancy Outcomes following Preconception, Early and Late Administration of Vaginal Micronized Progesterone for Recurrent Pregnancy Loss

M. Russu, R. Stănculescu, Ş. Nastasia, M. Păun, N. Mubarak1, J.A. Marin1, I. Lachanas

Abstract: Pregnancy outcome following preconception to 36th week of pregnancy treatment with vaginal micronized progesterone (VMP) for recurrent pregnancy loss. We prospectively analyzed 96 cases divided in three groups (differentiated by the moment of two previous pregnancy losses): 32 cases - group A - during the first trimester, 6 cases - group B - during the third trimester [treated with Folic Acid (FA), 200 mg/day VMP (14 days/month, luteal phase), continued after positive pregnancy test until 36th week], and 58 cases in the control group (C) on placebo. Primary outcomes included: time to conceive, gestational age at miscarriage/preterm birth, birthweight, Apgar scores, congenital malformations, composite neonatal morbidity, oxygen supplementation, mechanic ventilation. Secondary outcomes included: stillbirth, newborn death before discharge, maternal weight gain, maternal morbidity; hospitalization for threatened abortion/preterm birth. Student t test /ANOVA. Primary outcomes: fetal weight: controls: 2506.1±699.21g, group A: 3100 ± 489.41g (P=0.001 vs. control); group B: 3216 ± 537.27 g (P=0.022 vs. control); Apgar Scores: 1/5 minutes: controls: 8.05 ± 1.98/ 8.2 ± 1.99, group A: 8.45 ± 1.53 (P=0.40 vs. control)/8.77 ± 1.11 (P=0.21 vs. control), group B: 4.83 ± 4.57 (P=0.14 vs. control) / 4.83 ± 4.62 (P=0.13 vs. control); umbilical cord blood pH when Apgar <7/5 minutes: controls: 7.20 ± 0.19, group A :7.14 ± 0.34 (P=0.81 vs. control), group B : 6.55 ± 0 (P=0.0001 vs. control). GA at delivery: 24-28 weeks (0/0/2 in group A/B/C); 29-34 weeks (1/1/16 in group A/B/C); ≥ 35 weeks (21/5/23 in groups A/B/C). Malformations: 2 hypospadias (group A, control), 1 cryptorchidism, 1 hydrocele, 1 umbilical hernia (control); Neonatal morbidity: Respiratory Distress Syndrome: 2/1/5 (group A/B/C), no: BPD, IVH, NEC. Secondary outcomes: 25 miscarriages; 4 fetal deaths before discharge (0/2/2-group A/B/C); maternal weight gain: control: 11.95 ± 4.75, group A:16.77 ± 5.71 (P=0.001 vs. control), group B: 14.33 ± 3.32 (P=0.24 vs. control) gestational hypertension [group B: 2 (7.1%), controls: 3 (19%)], no gestational diabetes; hospitalization for threaten abortion (8 vs. 20 controls)/ preterm birth (10 treated vs. 18 controls). The study suggest that VMP preconception to 36 weeks gestation in recurrent pregnancy loss is followed by reduction of: preterm birth before 34 weeks (13.6% treated vs. 36.6% controls), miscarriages (23.7% treated vs. 27,7% controls), increased birthweight (P=0.001, group A; P=.022 group B), less reduction of umbilical cord blood pH (P=0.0001- group B) when Apgar score <7/5 minutes, less neonatal morbidity (only RDS: 10.3% treated vs. 12.2% controls), insignificant difference in perinatal mortality; less fetal abnormalities, lower incidence of gestational hypertension (5.2% treated vs. 19% controls), no gestational diabetes, and hospitalization for miscarriage (28.6% treated vs. 48.8% controls), or preterm birth threaten (35.1% studied vs. 43.8% controls).
Keywords: progesterone, miscarriage, preterm birth, neonatal morbidity/ mortality