Recurrent miscarriage refers to spontaneous miscarriage
3 or more times, with a prevalence of about 1%, and even after detailed medical examination, the cause of miscarriage is unknown in half of the couples. Recurrent miscarriage is associated with a poor prognosis and affects the psychological well-being of the pregnant woman and her family members, and therefore requires active evaluation and treatment, but there is no effective treatment for this condition. Progesterone, which improves the endometrial status to facilitate embryo implantation, is important for the maintenance of pregnancy and is secreted by the corpus luteum in early pregnancy and supplied by the placenta from 8 to 12 weeks of gestation. Therefore, it is clinically important to explore the efficacy of progesterone in recurrent miscarriage. Recently, a multicenter, double-blind, randomized controlled clinical trial conducted by Coomarasamy scholars at the University of Birmingham Medical School, UK, and others, suggested that progesterone preparations given early in pregnancy did not increase the risk of fetal malformations but did not improve neonatal live birth rates or perinatal outcomes in patients with recurrent miscarriage of unknown origin, and the article was recently published in NEnglJMed. Cases were obtained from 36 hospitals in the United Kingdom and 9 hospitals in the Netherlands. Inclusion criteria: recurrent miscarriages of unknown origin at the age of 18 to 39 years with a desire to have children. Exclusion criteria: inability to conceive within the last 1 year, antiphospholipid syndrome, abnormal uterine morphology, chromosomal abnormalities in the couple, combination of underlying diseases such as diabetes or thyroid disease and systemic lupus erythematosus, anticoagulation therapy and other contraindications to progestogen use. After the first positive urine pregnancy confirmation (less than 6 weeks of gestation), the recurrent miscarriages were randomized into two groups: the test group was given 400 mg of vaginal progesterone gel twice/day, and the control group was given placebo until 12 weeks of gestation. The primary index was the live birth rate after 24 weeks of gestation, the secondary index was the gestational sac visible at 6 to 8 weeks of gestation, the fetal heartbeat visible at 12 weeks of gestation, and the gestational heartbeat visible at 12 weeks of gestation.
The secondary indicators were gestational week of miscarriage and delivery before 24 weeks of gestation, survival rate at 28 days after delivery, and congenital malformations. Perinatal evaluation indicators: preeclampsia, premature rupture of membranes, infants younger than gestational age, prenatal hemorrhage, mode of delivery and neonatal birth weight, cord artery blood PH, Apgar score and use of whistler support or not. From June 23, 2010 to October 23, 2013, a total of 836 women conceived spontaneously, in the progesterone group
404 and 432 in the placebo group, with a follow-up rate of 98.8% and a live birth rate of 65.8% in the progesterone group and 63.3% in the control group, with pregnancy rates (6 to 8 weeks), sustained pregnancy rates (greater than
12 weeks) and ectopic pregnancy, miscarriage, stillbirth and perinatal outcomes did not differ between the two groups. 533 pregnancies were delivered after 24 weeks in both groups, with a delivery rate of 3.8% before 34 weeks in the progesterone group and 3.7% in the placebo group, with no significant difference in the incidence of adverse pregnancy events between the two groups. The overall incidence of neonatal malformations was 3.5%, 3.0% in the progesterone group and 4.0% in the placebo group. There were no statistically significant differences in perinatal complications between the two groups. Previous studies have shown better efficacy of intramuscular progesterone, but controlled studies have shown that vaginal progesterone preparations are as effective as intramuscular in reducing the risk of preterm delivery and are easy to use. Therefore, in patients with recurrent miscarriage of unknown origin, progesterone preparations given early in pregnancy, although safe and without increased risk of fetal malformations, do not improve live birth rates or perinatal outcomes.