Introduction
The use of the intrauterine device (IUD) for contraception is highly common among women. It has been reported in 2019 that worldwide 159 million women use IUDs for contraception purposes [1]. The Popularity of IUDs lie in their long-lasting acting mechanism, easy application, and reversible nature. However, the IUD application can cause several adverse side effects. Cramping/pelvic pain, abnormal bleeding, menorrhagia, and pelvic infection are among the most common ones. The severity and duration of these adverse symptoms determine the patient’s compliance. Approximately 10-15 % of women using copper IUDs have it removed due to menorrhagia [2]. Therefore, treatments that address and alleviate these adverse symptoms have been the focus of research concerning contraception with IUD. Neural therapy (NT) is a treatment modality that could be used in the treatment of these adverse effects. NT or also referred to as therapy with local anesthetics (TLA) is the diagnostic and therapeutic application of local anesthetics (LA). In addition to the short-term effects of LA in regional anesthesia through their inhibition of the depolarization of neurons leading to the disruption of the neuronal conduction, LA also manifest prolonged therapeutic effects through long-term action mechanisms. These mechanisms either rely on the modulation of the autonomic nervous system (ANS) by enhancing the sympatholytic activity or on the anti- inflammatory characteristic of LA [3, 4]. Through these prolonged action mechanisms, acute or chronic pain, functional disorders, vegetative disorders, and chronic inflammation can be treated with NT/TLA [5, 6]. Multiple sclerosis [7, 8], musculoskeletal diseases, gynecological disorders [9, 10], and chronic pain [11, 12] are among the disorders in which the benefits of NT/TLA have already been shown.

In this study, we aim to evaluate the effectiveness of NT/TLA treatment on pelvic pain, pelvic/vaginal infection, and abnormal vaginal bleeding following IUD application to determine whether it can be offered as a treatment option to those patients suffering from the adverse side effects of IUDs.

Patients who visited our family planning clinic and opted for IUD application for contraception purposes were also offered NT/TLA treatments. 40 patients who matched the inclusion criteria and received IUDs and NT/TLA treatments were included in the study group and 41 patients who only received IUDs were included in the control group. All patients received copper IUDs and none of them were on additional hormonal treatment. Before the insertion of IUD, women in the therapy group received NT/TLA treatment with 6 ml of 1 % procaine injected transvaginal into the cervix at 5 and 7’o clock localizations. Following IUD insertion, another 6 ml of 1 % procaine was injected into the Frankenhauser ganglia bilaterally. A final dose of 8 ml of 1 % procaine was injected into the abdominal trigger points and intracutaneously into the L4-S4 dermatomes as quaddies. See literature for detailed information on the injection techniques [5]. Patients rested for approximately 30 minutes before discharge to avoid any side effects that might occur due to LA injections such as dizziness and orthostatic dysregulation. All NT/TLA treatments were applied by a gynecologist who is also a certified neural therapist.

Patients were asked to come for a control follow-up one month after receiving their IUDs. At the control visit patients’ post IUD pain was routinely evaluated using a visual analog scale (VAS) from 0 to 10; 0 indicating no pain and 10 being severe pain. Patients were also asked to report if they had experienced any prolonged or heavy menstrual bleeding, non-menstrual bleeding, or spotting, and if they observed any vaginal discharge, vaginal discomfort, or fever indicating a vaginal/pelvic infection. At the follow-up visits, patients also received a routine vaginal inspection and transvaginal ultrasound examination to control the location of IUDs as well as for further assessment of vaginal/pelvic infection or abnormal bleeding.

Data analysis was performed by SPSS (IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp.). The frequency and percentage of the categorical variables and the median and range values of the nominal and continuous variables were presented. The study groups were compared using the Student t-test for parametric variables and the Mann Whitney U test for the non-parametric variables. The categorical variables were compared using the Pearson chi-square test. A p-value of <0.05 was considered statistically significant for all calculations.

There are several application techniques of NT/TLA [5, 13]. The most commonly used technique is the local subcutaneous application of LA directly on the symptomatic area (local therapy). Another frequently used technique in the treatment of myofascial trigger points. Injections applied to these trigger points ease the associated symptoms. Ganglia injections are categorized under the regional therapy modality of NT/TLA. Another treatment modality of NT is segmental therapy. The term ‘segment’ refers to the projections of autonomic innervation of an organ through neuronal reflex arcs on a dermatome, myotome, sclerotome, neurotome, and angiotome. These viscera-cutaneous projections are also called Head Zones [14]. The connection in a segment is not only neuronal but also functional. Thus, LA applied to a dermatome treat the associated organ. In this study, a combination of these techniques was used to address the adverse effects of the IUD application.

A literature research revealed several studies regarding the use of LA for pain relief during IUD insertion. [15, 16 and 17]. According to a systematic review and network meta-analysis conducted by Samy et al. local application of lidocaine-prilocaine cream is the most effective treatment of IUD insertion-related pain [18]. Although the administration of nonsteroidal anti-inflammatory agents has been recommended in the management of long-term pain/uterine cramping following IUD application, there is neither enough data in the literature to support their efficacy nor data on the application of other analgesic/anti-inflammatory agents. Therefore, this study was unique in its design to evaluate the long-term effects of LA on pain/uterine cramping related to the IUD application. According to the current study patients who received NT/TLA treatments experienced less pain during the one-month follow-up period when compared to patients who did not receive any pain management. This might be due to the modulatory effects of LA on uterine contractility, which was demonstrated by Weinschenk et al. on swine models [19]. Furthermore, the sympatholytic activity of LA disrupts the synergy between the parasympathetic and sympathetic nervous system’s effect on uterine contraction leading to uterine relaxation and pain relief [3, 20 and 21].

In addition to pain/uterine cramping, pelvic, and/or vaginal  infection can also develop following IUD insertion, especially during the first 20 days [22]. It is known that the insertion of an IUD can contaminate the cavity by pushing vaginal and cervical bacteria into the uterus [23]. Therefore, aseptic IUD insertion techniques reduce the risk of infection [24]. Thus, the significantly lower levels of infection observed in the NT/TLA treatment group can be explained by the transvaginal application of LA prior to IUD insertion, since LA also have antimicrobial characteristics. [9, 25].

The local inflammation caused by copper-containing devices, which is their main action mechanism, can lead to abnormal bleeding and/or menorrhagia. Through the anti-inflammatory characteristics of LA, a reduction in the bleeding was expected in this study [4]. However, a significant difference between the control and the study group was not observed. This might be due to the short follow-up period of the study. Since modulating inflammation is a long-term process, longer follow- up periods for 2 or 3 months might have yielded different results. Furthermore, sympatholytic activation of the ANS by LA leads to enhanced vasodilatation in the uterus [3, 20]. The vasodilatation might have counteracted the anti-inflammatory process initiated by the LA application resulting in abnormal bleeding during the first month following the IUD application.

The retrospective design of the study is one of its limitations. However, since all patients who opted for IUD application were routinely offered NT/TLA treatments, and all of them who gave informed consent were included in the study a selection bias was eliminated. Furthermore, the control group was randomly chosen from the women who received an IUD application without NT/TLA treatments during the same period of time. Due to this randomization, a difference in gravidity and parity between the control and the study groups could be observed. One could argue that this difference might have interfered with the comparability of the groups. However, according to literature, the only difference between nulliparous or women who delivered only by cesarean section and multiparous women regarding IUD insertion is observed at insertion where the former experience more pain [26]. Since the comparison of pain, infection, and bleeding was performed at the one-month follow-up, not right after IUD insertion, the difference between gravidity and parity did not affect the results of this study. The gravidity and parity were significantly higher in the study group. Whether gravidity and/or parity affect women’s decisions in opting for supportive peri-IUD insertion analgesic/anti-inflammatory treatments can be addressed in a future study.

In this study it has been demonstrated that the application of LA leads to IUD-associated pain relief and decrease the rate of infection whereas their effects on IUD-associated abnormal bleeding are still uncertain. LA in the form of NT/TLA treatments can be used in the management of adverse effects associated with IUD application. Their positive effect on pain and infection can increase patient’s compliance in the use of IUDs for contraception.

Disclosure statement: The authors have no conflict of interest to declare.

Funding Sources: This research did not receive any funding.

Data availability: Raw data is available upon request.

Ethical approval: The study was conducted in accordance with the ethical standards of the Declaration of Helsinki. Ethical approval was not  obtained  on  the basis of the retrospective design of the study. However, it was registered to ClinicalTrials.gov (NCT 04379102).

Author Contributions
NT treatments were performed by P.Y.B.
N.F.T.S. did data collection. N.F.T.S.
P.Y.B. wrote the manuscript with support from K.B.C.
C.K. H.N. supervised the project and contributed to the final version of the manuscript.