Can treatment with nitric oxide donors improve pregnancy outcome in patients with history of unexplained recurrent early pregnancy loss?

Comparative study between placebo vaginal tablets and the nitric oxide donor isosorbide mononitrate 20 mg tablet applied vaginally for treatment of unexplained recurrent early pregnancy loss

Status

Completed

Phases

Unknown

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12616001494426

Enrollment

225

Registered

2016-10-27

Start date

2013-01-01

Completion date

2014-01-01

Last updated

2020-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

Objectives: Impairment of endogenous nitric oxide synthesis is claimed a subtle cause of recurrent pregnancy loss. The present study evaluates treatment with the nitric oxide donor isosorbide mononitrate. Methods: Two hundred twenty five nulliparous with history of two consecutive unexplained pregnancy losses during the first trimester were randomized to a control group (120 cases) treated with placebo vaginal tablets and a study group (105) treated with isosorbide mononitrate 20 mg applied vaginally. Treatment started from day 21-23 of the cycle until menstruation and continued if pregnancy occurred until the end of the first trimester. Vaginal color Doppler ultrasound was done before treatment and at 12 weeks gestation to measure uterine artery resistance and pulsation indices. The outcomes of pregnancies in both groups were compared and statistically analyzed. Results: The study group had significant higher take-home baby rate, significant lower pregnancy loss and preeclampsia rates and lower mean uterine artery resistance and pulsation indices at 12 weeks gestation (p<0.05). Conclusions: Treatment of unexplained recurrent pregnancy loss patients with the nitric oxide donor isosorbide mononitrate is associated with better pregnancy outcomes.

Interventions

1-.A control group (120 cases) treated with placebo vaginal tablets once daily and a study group (105 cases) treated with isosorbide mononitrate 20 mg tablet applied vaginally once daily. 2-Treatment started from cycle day 21-23 to 12 weeks gestation if pregnancy occurs. If pregnancy does not occur participant repeat treatment next cycle at day 21-23. 3- Adherence to treatment was confirmed by empty drug packet return 4- A control group (120 cases) and a study group (105 cases).

Study design

Allocation

Randomised controlled trial

Primary purpose

Treatment

Eligibility

Sex/Gender

All

Age

18 Years to 30 Years

Healthy volunteers

Inclusion criteria

The study included 225 patients with the following inclusion criteria: 1- Nulliparous aged 18-30 years, house-wives and nonsmokers. 2- History of two consecutive failed clinical pregnancies from the same husband during the first trimester and confirmed by ultrasound. 3- Normal levels of lupus anticoagulant and anticardiolipin IgG and IgM on two or more occasions at least 12 weeks apart. 4- Normal uterine cavity and no pelvic pathology diagnosed by 3D/4D ultrasound. Hysterography, Sono-hysterography, hysteroscopy and laparoscopy was done in few suspicious cases. 5- Normal blood glucose and hemoglobin A1c levels. 6- Normal serum TSH, serum prolactin and mid luteal phase serum progesterone levels >10 ng/ml. 7- Cytogenetic study of the parents was done for 14 patients who had the third loss during the study and feature no balanced reciprocal translocations.

Exclusion criteria

Exclusion criteria include patients with cardiac disease, hypertension, sensitivity to NO donors and cases of interim ectopic or molar pregnancy or blighted ovum.

Outcome results