Long-acting reversible contraceptives, such as intrauterine devices, can dramatically reduce the risk of unwanted births (1). Unintended pregnancy is most common among adolescents and young women (2). A copper intrauterine device IUD is recommended as a first-line contraceptive treatment for sexually active teenagers (3). One of the most significant hurdles to IUD use in adolescents and young women is the fear of painful insertion (4).
Furthermore, clinicians' misunderstandings about the suitability of IUD usage in teenagers and young nulliparous women hinder this very effective method of contraception from being recommended. (5) IUDs, on the other hand, can be implanted in both parous nulliparous and nulliparous women (6). Intrauterine contraception with copper is an appealing choice for teenagers who want long-term, continuous contraception with fast fertility recovery (7).
Many authorities suggest IUDs as first-line choices for teenagers (8, 9).
According to one research, nulliparous women's uterine cavities are narrow, and conventional-framed IUDs do not fit well (10), which might lead to increased discomfort during insertion, restricting IUD use in nulliparas (10, 11).
Finding an effective pain reliever might boost IUD use and reduce the incidence of unplanned births among teenagers and young women, which can have negative social, economic, and physical health consequences (12).
In obstetrics, INH is utilized for cervical ripening and labor induction. According to research, INH is as good as or better than misoprostol for cervical softening during labor induction (13). Before diagnostic and operative hysteroscopic procedures, INH was also utilized for cervical ripening and priming in nulliparous women. It was effective and safe in terms of hysteroscope entrance ease, procedure discomfort, and side effects (14, 15).
The role of INH administration prior to IUD implantation has never been investigated, especially in adolescents and young women under the age of 22, for whom analgesia is considered vital. In this trial, we evaluated the effectiveness and safety of self-administered INH 900 mg vaginally to placebo in decreasing discomfort during a copper T380A IUD implantation in adolescents and young nulliparous women.

 

We performed a randomized controlled study at the Family planning clinic of the Obstetrics and Gynecology department at a tertiary university hospital from March 2020 to September 2020. The scientific departmental committee granted us ethical permission in advance. All ladies who decided to participate completed a written informed consent form after getting a detailed overview of the procedure, potential side effects, and complications.

Patients who desired copper T 380A intrauterine contraception were eligible for the trial if they were 18-22 years old, had a negative pregnancy test, didn't take any analgesics in the 48 hours preceding up to the IUD insertion, and had no previous pregnancies longer than 13 6/7 weeks.

Women who had a recent diagnosis of pelvic inflammatory illness, active vaginitis, or cervicitis, were presently pregnant or were pregnant within six weeks of study admission, or had a history of cervical surgery were excluded. The study excluded women with undiagnosed abnormal uterine bleeding, World Health Organization Medical Eligibility Criteria category 3 or 4 precautions to a copper IUD, a prior attempted or successful IUD insertion, fibroids, or other uterine abnormalities distorting the uterine cavity, and a known allergy or contraindication to INH.

We followed standard clinic procedures for pre-procedural counseling and evaluation: we took a full medical history and performed abdominal and vaginal exams. Participants filled out a demographics form on the day of their copper IUD insertion, and the research nurse gave everyone a urine pregnancy test.

We used a 1:1 allocation ratio and a computer-generated random numbers table to divide women into two groups. The computerized randomization list was created by a statistician who was not directly engaged in the investigation and kept the key for group allocation hidden from investigators until the trial was completed. 12 hours before the surgery, the first group received 900 mg vaginal INH. The second group got a placebo designed by the department of pharmaceutical chemistry at Aswan University's Faculty of Pharmacy to be identical to INH pills in form, size, and color. Tablets of INH and placebo were placed in opaque, sealed envelopes with consecutive serial numbers.

They were utilized in the sequence in which the women were present. The allocation was kept a secret from the participants, study personnel, and suppliers.

The clinic nurse then booked all the participants for a second IUD installation appointment, advising them to keep the study medicines refrigerated and implant them as deeply as feasible in the posterior vaginal fornix 12 hours before their T380A IUD placement appointment. We sent automated reminders to participants' phones at the time of study medication delivery. Furthermore, one of the study's investigators called all participants to remind them about the study and verify that they took their medications on schedule.

The doctors implanted intrauterine contraceptive devices from the third to the fifth day of the menstrual cycle. The IUD utilized was Copper T380A (Pregna Copper T 380A, Pragma, Egypt), and all of the providers employed the manufacturer's recommended procedure for IUD insertion (16). After placing a speculum, cleaning the cervix with antiseptic, applying a single-toothed tenaculum, and sounding the uterus to measure its length, the inserting physicians inserted the IUD without ultrasound guidance. We tested whether Hegar dilators with a diameter of four millimeters or less could pass through the internal cervical os without resistance before copper IUD placement to assess the degree of cervical dilatation. Patients were not in any pain or discomfort since the physicians placed Hegar dilators softly and without force.

The main outcome measure was the difference in IUD insertion ease scores between study groups (as reported by physicians responsible for IUD insertion). On a 10-cm VAS scale, this score ranges from 0 to 10, with 0 indicating very simple insertion and 10 indicating exceedingly difficult insertion.

Secondary outcomes were the proportion of women with cervical dilatation less than four millimeters and the level of patient-perceived pain at the moment of IUD insertion, as determined by a visual analog scale. The VAS scale is evaluated from 0 to 10, with 0 signifying no discomfort and 10 indicating the most excruciating pain.

On a VAS sheet, the participant was asked to select the point that corresponded to the level of pain she had experienced. At the completion of the procedure, the providers reported the ease of insertion using the ease of insertion score (ES).

We asked for fever (oral temperature 38°C), nausea, vomiting, shivering, diarrhea, and cramps, all of which were documented shortly before IUD implantation, to confirm that they were caused by the medicine rather than the insertion procedure. As mentioned by the patients, we also recorded postprocedural bleeding five minutes after the procedure, vasovagal reaction, uterine perforation, failed insertions, and insertion time.

The lowest clinically meaningful difference in ease of insertion scores was determined at o.76 (i.e., the ease of insertion score for the INH group should be lower than the placebo group by o.76).

Each study group needed at least 90 people to detect this difference with 90% power and a 0.05 alpha level. To accommodate for attrition or disqualification of participants, we raised the expected sample size by 10%. A total of 200 persons were included in the study (100 patients in each group) (16).

 The Statistical Package for Social Sciences (SPSS) version 16 was used to enter data and perform statistical analysis. Numbers and percentages were used to describe qualitative data. The Fisher's exact test and the Chi square test were employed to compare groups, if needed.

After checking for normality using the Kolmogorov-Smirnov test, quantitative data were presented as means (SD) or medians. The independent samples t-test was used to compare groups with normally distributed data, whereas the Mann-Whitney U test was used to compare groups with non-normally distributed variables. We estimated odds ratios and their 95% confidence intervals. Statistical significance was defined as P-value<0.05.