الفهرس 
Comparison of Effectiveness and Safety of Combination of Misoprostol and Nitric Oxide Donor (Isosorbide -5- Mononitrate) versus Misoprostol Alone in Induction of Midtrimester Abortion (RCT)
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Abstract
Miscarriage refers to the loss of a pregnancy before 24 weeks. It is a common complication of pregnancy, occurring in 12%–30% of all clinical pregnancies and even more if unrecognized biochemical pregnancies are included (Hu et al., 2018). Second trimester or mid trimester is a period ranging from 13 to 26 weeks of gestations (Cunningham et al., 2021)
A missed abortion is a miscarriage in which the dead embryonic tissues are still in uterus or lacking expulsion. The incidence of missed abortion among spontaneous miscarriages is 2.6-9.4% (Dugas and Slane, 2019). Missed abortion is diagnosed in patients previously estab¬lished as being pregnant, in the present the following signs; smaller than expected uterus, closed uterine cervix, no history of recent profuse uterine bleeding or in case of undetectable fetal heart beat by ultrasound (Linnakaari et al., 2019).
Miscarriages occurring in the second trimester of pregnancy are uncommon and often unexpected. The incidence of miscarriage in the second trimester varies depending on the gestational age in weeks that is used in definitions and depending on whether the pregnancy has been dated and evaluated using ultrasound. In low risk women the risk of miscarriage in the second trimester is approximately 0.5% (Westin et al., 2007).
Once the diagnosis of missed abortion is made, counseling is done and the patient can then be offered different types of management depending on their clinical status and patient’s choice. Medical termination is one of the treatment options using some drugs to open the cervix and /or expel the uterine contents (Brioude et al., 2018).
Cervical ripening is clinically diagnosed by softening, effacement, and dilatation of the uterine cervix (Evbuomwan and Chowdhury, 2021).
Misoprostol, a synthetic 15-deoxy-16-hydroxy-16-methyl analogue of naturally occurring prostaglandin E1, was marketed for use in the prevention and treatment of peptic ulcer disease. It is inexpensive and can be stored at room temperature. Although not registered for such use, misoprostol has been widely used in Obstetrics and Gynecology for cervical priming, medical abortion and induction of labor (Subaha, 2019).
It is not uncommon to identify particulate remnants of the tablets in the vagina at the time of repeated dosing, indicating that dissolution and absorption are variable and incomplete. Misoprostol could be taken either vaginally or orally, it has short half-life (10-20min) (Zhuo et al., 2019).
The nitric oxide (NO) donors are effective at inducing cervical ripening during the first trimester, prior to medical termination of pregnancy. These agents usually have fewer adverse effects than the prostaglandin analogue (Muhammed et al., 2019).
In contrast to the stimulatory actions of prostaglandins, activation of the NO system leads to myometrial relaxation and can be used to successfully treat intra-partum fetal distress caused by uterine hypertonus (Dülger et al., 2018).
We hypothesize that the cervical ripening effects of nitric oxide donors and of prostaglandins may be additive. If this hypothesis is correct, this would allow a small dose of nitric oxide donor to be given with a small dose of prostaglandins to affect cervical ripening. Such a strategy may reduce the side effects associated with large doses of prostaglandins alone.