In this study we found that 86% of the women succeeded in the treatment of early miscarriage with Misoprostol. Only 19,2% of the patients showed side effects with nausea being the most frequent one (followed by vertigo, diarrhea, vomiting, headaches and fever) making Misoprostol safe, efficient and low in side effects for early miscarriage.
Cesarean sections in previous pregnancies seem to have a negative impact to the effectiveness of the drug and showed tendencies to be a significant parameter which lead to more frequent secondary curettages (suction aspiration) after administration of Misoprostol (p = 0.083).
This aligns with findings from two Cochrane analyses [11][12] which also state that it shows high patient satisfaction besides being a safe and effective method. Similar results are seen in a systematic review from 2020 [13]. Although the study focuses on medical induced abortions, which was an exclusion criteria in our study, it nevertheless gives an outlook to safety in various medical indications. Another review from 2021 [14] reaches similar conclusions and success was seen in 88–93%. However, in this study Mifepristone 200mg was administered 24–48 hours before Misoprostol and Misoprostol taken sublingually or vaginally instead of orally, hence a comparison is only partially possible.
The various administration routes of Misoprostol present another interesting outlook. In our study we only administered the drug orally due to psychological concerns of taking the vaginal route while having an abortion, the pill not dissolving properly due to bleeding or not dissolving sublingually because of the big size and its overall manageability. In different guidelines such as the WHO, AWMF, FIGO and NICE, Misoprostol for early abortion is given differently. The WHO [15] suggests oral or sublingual route for incomplete abortion, AWMF [16] suggests vaginal, sublingual or buccal, FIGO [17] suggests vaginal or sublingual for missed abortion and eventually oral for incomplete abortion and NICE [18] suggests vaginal or oral route if wished by the patient. A recent RCT from 2019 [19] comparing the sublingual versus vaginal route of Misoprostol for first trimester missed abortion came to the conclusion that the sublingual route was significantly more successful in complete abortion than the vaginal route with significant shorter length of induction-expulsion time than the vaginal group (12.3+-3.1h vs. 16.4+-4.2h; p < 0,001). It did state though, that side effects occurred significantly more frequent in the sublingual arm than in the vaginal.
In an older RCT [20] the oral route was not more effective than the vaginal route but the side effects were significantly more frequent in the oral group, thus emphasizing the results from 2019.
In terms of safety and manageability of taking Misoprostol in an outpatient setting a recent national cohort study from BJOG [21] compared the outcome of early medical abortion without ultrasound via telemedicine by administering Mifepristone and Misoprostol sublingual, vaginal or buccal. They found out that it has no disadvantage to the patients taking Misoprostol in an outpatient setting and it is found to be effective and safe. However, this study only focused on induced abortions and had the possibility of providing the patients with a 24-hour hotline in case of unusual events, concerns and emergencies which can be problematic to some clinics in terms of finances or staff shortages, but it does state an interesting foresight to the future of telemedicine.
Although the results in our study did not reach statistical significance, the two-sided chi-square test showed a tendency towards more frequent secondary curettages after being treated with Misoprostol in women with increasing number of cesareans in past medical history (exact value two-sided 0.083). Further tendencies could also be seen in women with cesarean deliveries in the past medical history and the number of Misoprostol cycles undertaken. Not statistical significant but as well there seems to be more frequent secondary curettages with only one cycle of Misoprostol administered (exact value two-sided 0.057 at p < 0.05) meaning premature termination of therapy as wished by the patients. Our findings are in line with the conclusions from an observational 10 year study [22] which found out that there is a significant decrease in successful treatment with misoprostol depending on previous cesarean sections (p = 0.002) and parity (p = 0.048) of the women. The history of one or more cesarean sections led to significantly more failure in medical treatment (p = 0.001). This is confirmed by a recent RCT from 2021 [23] stating that history of cesarean sections lead to more failure in treatment. Correspondingly a recent study from 2022 [24] examined predictive parameters to failure in treatment with Misoprostol in women with one or more cesarean sections in the past. It showed that the width and the blood flow signal of the residual seen via ultrasound were both independent predictors for complete abortion (p = < 0.05). The rate of complete miscarriage was higher in women without blood flow shown in the ultrasound and residue of less than 1cm.
The significance we found in double endometrial stripe thickness after the second cycle of Misoprostol in women who later underwent curettage compared to women without curettage (p = 0.012) could not only delivery a possible prognostic marker but is also in align with findings in the literature. In a retrospective study[25], they found that every additional millimeter of endometrial stripe thickness led to an additional 8% chance of undergoing further surgical procedure. It should be mentioned though, that the study not only included miscarriage but also induced abortions, vaginal deliveries and caesarean sections with material retention, hence a direct comparison is only partially possible.
All of the above findings should be considered when treating patients in the future.
The strengths of our study are: i) minimal loss of follow-up regarding complete abortion or secondary curettage; ii) systematically performed follow-up examination in house in a standardized manner.
The retrospective character and thus leading to recall bias of the patients, especially regarding side effects (insufficient information given by the patients) represent limitation of our study. Our results describe no correlation between physical parameters such as age or weight, parity or previous vaginal deliveries and the success of Misoprostol. Still, our study strengthens former results from other studies regarding the effectivity and safety and gives additional assumption that previous pregnancies and deliveries do have an impact to the outcome. Because of recall bias it is possible that individual findings to side effects are left unmentioned in follow-up examinations but as we attended a standardized questionnaire in every follow-up visitation we collected at least one answer from every patient and the results are similar to aforementioned studies.
In conclusion, our study provides evidence that Misoprostol is safe and has few side effects. Thus, also considering other mentioned studies we propose to encourage patients and gynecologists in choosing the medical route administering Misoprostol instead of standardized suction curettage for early miscarriage. However, patients with a history of cesarean section may need to undergo a more detailed medical examination to find out whether or not they would be suitable for Misoprostol. We suggest that larger evaluations in clinics are needed to make the administration even safer and more predictable also to avoid a prolonged course of treatment in this exceptional situation. This scientifically evidence could encourage pharma industries to register Misoprostol not only as a gastric ulcer treatment but to fully license it as a basic and much needed drug in gynecology.