[INSERT TABLE 3]
Finally, the outcomes demonstrated an 83.33% success rate in those patients treated by misoprostol alone. While those groups treated by misoprostol plus oxytocin and misoprostol plus methylergonovine illustrated a success rate of 93.333%. The net results showed neither any statistical significance in the three different medication therapies (P=0.329) nor any adverse effects associated with them.
Discussion
The result obtained in the present study confirms an improved efficacy of the medical therapy of misoprostol either combined with oxytocin or with methylergonovine in successful expulsion of the RPOC. Although treatment by misoprostol alone (83.3%) has not resulted in remarkable statistical significance, greater therapeutic efficacy was reported in the groups (93.33%) treated by a combination of misoprostol plus oxytocin or misoprostol plus methylergonovine. Moreover, by designating the degree of persistent residual tissues in the patients, it was concluded that those patients treated with misoprostol plus oxytocin had the best outcome compared to the other groups. Likewise, all the patients treated with other medications showed a sufficient successful rate of RPOC expulsion.
Kaviani et al. in 2006 concluded that ’the efficacy of methylergonovine in the successful expulsion of retained pregnancy tissues in patients with incomplete abortion showed to be 94.6%’. Additionally, Niroumanesh et al. reported results similar to our findings 12. Another study carried out by Petca et al. in 2019 compared the effectiveness of simultaneous administration of misoprostol and oxytocin (M&O) versus misoprostol and mifepristone (M&M) on abortion in the second trimester in over 108 patients. Their study further illustrated that administering M&M simultaneously resulted in greater expulsion rates within 12 hours compared to M&O, with the latter regimen demonstrating synergistic benefits, with lower expenses and satisfactory I-AI 22. This study, like the previous one, is in coherence with our study.
Misoprostol is a prostaglandin E1 analog which is a uterotonic pharmacological agent and functions either by contracting the uterine smooth muscles or by dilation of the uterine cervix23. On the other hand, by increasing the permeability of uterine myofibrils to sodium, oxytocin causes uterine smooth muscle contraction. That is why this compound is frequently used to induce labor 24. Overall, these beneficiary medications aid to dilate the cervix gently which results in a drastic reduction in the subsequent complications of cervical dilation i.e. uterus perforation, cervix rupture, hemorrhage, incomplete fetal-placental delivery and infection, and pregnancy products expulsion. Besides, these medications help to avoid anesthesia and its complications in cases where complete abortion is necessary 25.
Although the mean age of all the patients in this study was 29.76±5.53 with no statistical significance in the three different groups, we discovered that age-related physiological factors have the potential to alter the outcomes. Niroumanesh et al. concluded that older multiparous patients with several histories of previous pregnancies were found to have more tendencies for surgical and curettage approaches as compared to the other patients 26.
Another conclusive point with regards to the mean age of the patient is that younger aged patients experiencing abortion need to be educated thoroughly about contraceptives and preventive methods, unlike the other age groups. However, this perspective might appear irrelevant to the current study aim.
Abnormal weight in the mothers has a crucial impact on fertility and sanitizations during a healthy pregnancy; that is why determining factors like BMI like weight and height can play a substantial role in abortion physiology. For this matter, all the patients were examined for BMI and blood pressure, but no statistical significance in these variables was noted that might have altered the outcomes. These findings were compatible with a study conducted by Ghasemi et al.in 201827.
After the prescription of drugs in the different groups, hemorrhage, pain, and spotting which are considered as pregnancy tissue expulsion associated complications were carefully evaluated. A persistent postpartum hemorrhage after fetus abortion signifies small fragments of trophoblast and decidua still retained in the uterus after fetal death or RPOC expulsion 28. There are various medical protocols developed to prevent bleeding after surgical abortion or labor. However, these protocols are continuously being modified to achieve better outcomes and higher rates of success29-31. Even though there is no evidence of significant difference regarding the severity of hemorrhage in three different groups in our study, but those given misoprostol plus methylergonovine showed very mild bleeding as compared to the other groups.
A causal-comparative study was conducted by Whitehouse et al. to compare the efficacy of medical management for bleeding prevention after surgical abortion in over 336 patients with a history of recent abortion in 2018. Their study discovered that 72% of the patients used contraceptive drugs to prevent bleeding, and among them, 83% preferred vasopressin over other drugs. Likewise, scientists declared that these patients also showed willingness for the intake of methylergonovine during the second trimester to control severe bleeding and then preferred misoprostol 15. Whitehouse et al’s discoveries are consistent with our findings. A year later, they conducted another study to illustrate oxytocin potency on the reduction of frequency rate of hemorrhage and blood loss and concluded that oxytocin as prophylaxis for bleeding does not result in a reduced number of interventions required to control the bleeding during dilation and evacuation (D&E) period between 18-24 week of gestation. However, it does reduce the bleeding intensity and hemorrhage frequency which was also in harmony with our study.
Methylergonovine and oxytocin are stimulators of uterine contraction which act directly on uterine smooth muscle and peripheral vasculature, especially uterine vessels, and thus reduce hemorrhage33,34. This topic supports our study by demonstrating that there is no significant statistical difference between oxytocin efficacy and other drugs used for the mentioned purpose.
Similarly, regarding spotting manifestation after abortion and medication intake, the analysis proved no significant difference in the manifestation of spotting between different study groups. This fact confirms the results obtained from the degree of hemorrhage reported from the participants.
Considering medication intake and postpartum pain followed by fetal abortion, our study has discovered that the combination of misoprostol plus methylergonovine showed the best efficacy in pain management. A varied number of guidelines published for pain management by various medical associations have recommended only a normal dosage of common analgesics 35,36. But, most of these guidelines describe neither specific medication type nor specific dosage in this scope. Moreover, the efficacy of analgesic protocols is limitedly studied in the literature, especially the protocols discussing the prevention and treatment of pain occurring post-miscarriage.
Although the World Health Organization (WHO) strongly recommends controlling, monitoring, and measuring the pain 37, even then they have not specified pain measurement methods in women with miscarriage during the first trimester.
A study conducted by Kemppainen et al. with the purpose of pain scaling during a medical abortion in early pregnancy reported VAS score of 75, and 91-54 for median and interquartile range respectively, in over 140 teenage and adult patients. Of all the women, 57.7% of them experienced severe pain (VAS=70) during abortion care. Also, 93.5% of these women needed additional opioid analgesics such as tramadol or oxycodone despite being administered with regular analgesics for prophylactic pain medication, like ibuprofen and paracetamol. Even though the misoprostol administration did not reduce the risk of pain recurrence, but even then, patients treated with misoprostol reported satisfaction38. According to Kari Braaten et al39, intravenous injections of sedatives were not useful to reduce the pain in patients with surgical abortion during the first trimester, in contrast to their study, due to administration of combined misoprostol and methylergonovine, severe pain remained uncovered and its manifestation occurred in none of the patients. It is noteworthy to mention that, methylergometrine can be also used to modulate the pain of origins except miscarriage; for example, Niño-Maldonado et al. reported positive efficacy of methylergometrine for migraine pain modulation in emergency settings 40.