Canadian Study on the Association of Pessary With Progesterone

Hypothesis: A standardized recruitment process could allow the inclusion of 0.9% patient (CI 95%: 0,78-1.04) among women receiving a 18-23 weeks ultrasound scan.

Recruitment: Participants will be recruited, in a three-step manner, among women appointing for the 18-23 weeks ultrasound scan; i) assessment of the cervical length by abdominal ultrasound, ii) an endovaginal ultrasound measurement will be performed if the cervical length is ≤ 30 mm, iii) enrollment and consent of the patient to the pilot study, under the confirmation of the presence of a short cervix (≤ 25 mm) by the endovaginal ultrasound.

Intervention: Vaginal progesterone (200 mg/day, PROMETRIUM®, Merck Canada Inc.) until 37 weeks. Perforated cerclage pessaries (Dr. Arabin GmbH \& Co. KG) will be placed in specialized clinic and will be removed at 37 weeks.

Size of the sampling and statistical analysis: This multicenter pilot study will be conducted in High-Risk Pregnancies Clinics in Quebec and in Ontario.

Over the 12 months period, the investigators expect to collect data from 26 000 abdominal ultrasounds. In accordance with the anticipated recruitment level of 0.9%, the investigators planned on enrolling 250 women. Within those women, 125 will be assigned randomly to the "progesterone" group and 125 to the "progesterone and pessary" group (1:1 ratio).

Perspective: This pilot study is designed to identify the challenges and provide strategies to deal with them in a larger study. Providing its feasibility, this study will lead to a definitive randomized controlled trial (including over 70 centers) to test the effectiveness of pessary and progesterone in preventing preterm birth.

• Prometrium (Drug), also known as Progesterone: Intravaginal use, off label, of Prometrium
• Dr. Arabin, cerclage pessary perforated (Device), also known as Pessary: A Dr. Arabin, cerclage pessary perforated will be inserted participants diagnosed with a short cervix

Primary outcomes

• Recruitment feasibility [Up to 24 weeks (18 to 42 weeks of gestation)]: According to the anticipated recruitment rate, 0.9% of women having an anatomy scan could be included (95% CI, 0.78- 1.04). We will determine the % of women included in the study (until the 42 week of gestation) over women that received a anatomy scan.

Secondary outcomes

• Preterm delivery [Before 34 weeks]: The secondary outcome is to determine the occurrence of spontaneous preterm births before 34 weeks in the progesterone alone group " without pessary harm ".

Sex: Female, ages: 18 Years to 45 Years, accepts healthy volunteers

Inclusion Criteria:

* patient with a short cervix equal to or less than 25 mm by transvaginal ultrasound
* gestational age between 18 (0/7) and 23 (6/7) weeks of gestation according to the results of the ultrasound of the first trimester, or by integrating the date of the last period
* patients who were informed of the study and agreed to sign the consent form.

Exclusion Criteria:

* pregnancy with a fetus with a major congenital malformation - regular and painful uterine activity - history of preterm premature rupture of membranes (PPROM) - active vaginal bleeding - complete and incomplete placenta previa - cerclage of the cervix in place - antecedent of conisation - multiple gestation - ballooning of membranes outside the cervix into the vagina - allergy/intolerance or hypersensitivity to progesterone or any of its ingredients - chronic medical conditions that would interfere with study participation or evaluation of treatment - vaginal administration of another drug.

• Results publication: Abdel-Aleem H, Shaaban OM, Abdel-Aleem MA, Aboelfadle Mohamed A. Cervical pessary for preventing preterm birth in singleton pregnancies. Cochrane Database Syst Rev. 2022 Dec 1;12(12):CD014508. doi: 10.1002/14651858.CD014508. PMID 36453699

• Jean-Charles Pasquier, MD, PhD, Principal investigator, Université de Sherbrooke