الفهرس 
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Abstract
Missed miscarriage is diagnosed when a non-viable pregnancy is identified on an ultrasound scan during the first 14 weeks of gestation. Often, women who have missed miscarriage are asymptomatic or have small amounts of vaginal bleeding or pain before the diagnosis is made (ACOG, 2018).
Misoprostol is a synthetic prostaglandin E1 analogue marketed as an oral preparation used to prevent and treat gastro-duodenal damage. However, misoprostol is used off-label for a variety of indications in the practice of obstetrics and gynecology, including medical management of miscarriage, cervical ripening before surgical procedures, and the treatment of postpartum hemorrhage. (van den Berg et al., 2019).
Nitric oxide donors induce production of matrix metallo-proteinases namely MMP-1 and MMP-9, which are essential for collagen degradation and also increases pro-inflammatory cytokines and prostaglandins production in cervical ripening process (Radulovic et al., 2009).
Isosorbide mononitrate have been used as cervical ripening agents in first trimester and for induction of labor at term (Duhan et al., 2011; Mirteimouri et al., 2020).
The present study aimed to assess the efficacy and safety of NO donors (isosorbide mononitrate) when combined with misoprostol in medical induction of first trimester abortion expecting that both drugs when used together will be of greater efficiency and associated with fewer side effects.
The current study was a randomized clinical trial carried out at the Obstetrics and Gynecology Hospital – Ain Shams University during time interval from April 2020 till December 2020 in which 50 women with first trimester missed miscarriage divided into two groups 25 participants in each group were admitted for medical induction of abortion.
group A (25 women): received misoprostol 400 mcg to be repeated every 4 hours in 2 doses
group B (25 women): received misoprostol 400 mcg in combination with 40 mg isosorbide mononitrate repeated every 4 hours in 2 doses.
o After administration of drugs, induction to expulsion time was noted and vital monitoring was done hourly. Patients were reassessed if vaginal bleeding or uterine contractions were noted otherwise repeat dose was given after 4 hours. Complete expulsion was performed by expert gynecologist under general anesthesia if needed and confirmed subsequently by ultrasonography.
o Documentation of number of doses of drugs, mean intraoperative blood loss and drugs adverse effect were done.
o Appropriate antibiotic cover was given if needed and patients were discharged in stable condition.
In misoprostol group 4 women (16%) aborted after the first dose and 6 women (28.6%) aborted after the second dose, while 5 women (20%) aborted after the first dose and 8 women (40%) aborted after the second dose in ISMN with misoprostol group.
The present study shows that there was no statistically significance difference regarding number of received doses and spontaneous expulsion among both groups
The mean time of induction to expulsion in misoprostol plus ISMN group was (230.0 ± 68.85) minute which was less than in misoprostol group (320.0 ± 72.27) minute. There was a highly statistically significance difference regarding mean induction to expulsion time among both groups with P-value (P<0.01).
In current study there was no statistically significant difference among both groups regarding main surgical complication as uterine infection and cervical injury according to it P-Value (p=0.637), (p=0.297) respectively.
Uterine infection occurred in 2 participants in misoprostol group and 3 participants in misoprostol plus ISMN group. While, cervical injury occurred in 3 participants in combination group compared with only one participant in misoprostol group.
Regarding drug adverse effects there was no statistically significant difference among both groups (P-value > 0.05).
Only headache occurred at a higher proportion among ISMN with misoprostol group (16%) compared to misoprostol group (4%)
On the other hand, colic occurred in the same proportion (12%) in each group.
In the current study there was no statistically significance difference between the two studied groups regarding intraoperative blood loss.
The mean intraoperative blood loss was 86.67 ± 39.94 ml in misoprostol group and 86.92 ± 50.56 ml in misoprostol plus ISMN group.
The present study concluded that the use of isosorbide mononitrate (ISMN) in addition with misoprostol in medical induction of first trimesteric abortion may be more effective than misoprostol alone but was associated with more side effects such as headache.