Evaluation of the Analgesic Effect of Intramyometrial Botulinum Toxin Injection Via Hysteroscopy in Pelvic Pain Suggestive of Dysmenorrhea

The response (favorable versus unfavorable) to the Patient Global Impression of Improvement questionnaire at 3 months following intra-myometrial injection. A response is considered favorable when the score of Patient Global Impression of Improvement questionnaire is 1 or 2. Patient Global Impression of Improvement questionnaire is self-assessment scale ranging from 1 (Very much improved) to 7 (Very much worsened).

Average intensity of dysmenorrhea evaluated using a numerical rating scale during the last menstrual cycle before injection, then at 3 and 6 months. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Maximum intensity of dysmenorrhea evaluated using a numerical rating scale during the last menstrual cycle before injection, then at 3 and 6 months. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Duration (in days) of dysmenorrhea during the last menstrual cycle before injection, then at 3 and 6 months.

Average intensity of non-menstrual pelvic pain evaluated using an numerical rating scale before injection, then at 1, 3, and 6 months. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Maximum intensity of non-menstrual pelvic pain evaluated using an numerical rating scale before injection, then at 1, 3, and 6 months. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Duration of non-menstrual pelvic pain (in days) evaluated before injection, then at 1, 3, and 6 months

Average intensity of pain during the most recent sexual intercourse, evaluated using an numerical rating scale before injection, then at 1, 3, and 6 months. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Sexual function assessed using the Female Sexual Function Index before injection, and then at 1, 3, and 6 months. The Female Sexual Function Index consists of 19 items assessing six dimensions of female sexual function (desire, arousal, pain, lubrication, satisfaction, orgasm). The total score ranges from 2 to 36, with sexual dysfunction defined as a score below 23.

Central sensitization to pain assessed using the Convergences PP score, before injection and at 3 months. The total Convergence PP score ranges from 0 to 10, with pelvic hypersensitivity defined as a score greater than or equal to 5.

Heavy menstrual bleeding assessed using the Higham score during the last menstrual period, before injection, and at 3 and 6 months. The Higham score is an objective assessment score of menstrual blood loss. Each day of menstruation, the patiente counts the number of pads or tampons used, referring to a visual chart. A score above 100 points corresponds to a blood loss of 80 mL, which defines menorrhagia.

General quality of life assessed using the The Short Form (36) Health Survey before injection, and at 1, 3, and 6 months. The questionnaire The Short Form (36) Health Survey is a multidimensional, generic scale, meaning it assesses health status regardless of the underlying condition, gender, age, or treatment. Its 36 items evaluate 8 domains: physical activity, physical role limitations, bodily pain, perceived health, vitality, social functioning, emotional state, and mental health. Each item is scored from 0 (lowest score) to 100 (highest score). At the end, a score for each SF-36 dimension is calculated based on the corresponding items, ranging from 0 (poor quality of life) to 100 (best quality of life).

Disease-specific quality of life assessed using the Endometriosis Health Profile EHP-5 questionnaire (it is the short version of Endometriosis Health Profile EHP-30) before injection, and at 1, 3, and 6 months. This short questionnaire includes only 11 out of 30 questions, to which patients must respond with Always, Often, Sometimes, Rarely, or Never. This questionnaire ranging from 0 (the best health status) to 44 (the worst health status).

Number of days of school or work absenteeism in the past month, assessed before injection and at 1, 3, and 6 months.

Anxiety assessed using the State and Tait Anxiety Inventoy scale-Y before injection and at 3 months. This State and Tait Anxiety Inventoy scale-Y includes two distinct scales for assessing state anxiety (STAI Form Y-A) and trait anxiety (STAI Form Y-B). The Trait Anxiety scale consists of 20 items and assesses the individual's general tendency to experience anxiety. Scores range from 21 to 77.

The State Anxiety scale also includes 20 items and measures a temporary anxious mood (stress). Scores range from 20 to 80.

Depression evaluated using the Beck Depression Inventory-II before injection and at 3 months. This is a self-administered questionnaire consisting of 21 items. Each item includes 4 statements corresponding to increasing levels of symptom intensity, rated on a scale from 0 to 3. The total score is obtained by summing the scores of the 21 items. The score can be interpreted according to the following four categories: no depression (score < 10); mild depression (10 < score < 18); moderate depression (19 < score < 29); and severe depression (score > 30).

Global improvement percentage (0-100%) assessed at 1, 3, and 6 months.

Pain intensity during the procedure assessed via numerical rating scale. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Pain intensity at 5 minutes post-procedure, assessed via numerical rating scale

Adverse events related to the injections, recorded immediately postoperatively, and at 1, 3, and 6 months.

Emergency visits following the procedure, assessed at 1 month.

Exploratory analysis for the MEOPA subgroup: Primary outcome. The response (favorable versus unfavorable) to the Patient Global Impression of Improvement questionnaire at 3 months following intra-myometrial injection. A response is considered favorable when the score of Patient Global Impression of Improvement questionnaire is 1 or 2. Patient Global Impression of Improvement questionnaire is self-assessment scale ranging from 1 (Very much improved) to 7 (Very much worsened).

Exploratory analysis for the MEOPA subgroup : procedural pain. Pain intensity during the procedure assessed via numerical rating scale. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Exploratory analysis for the MEOPA subgroup: willingness to repeat the intervention. The response is rating Yes or No.

Exploratory analysis for the MEOPA subgroup: adverse events.

Exploratory analysis for the MEOPA subgroup : emergency visits.

Exploratory analysis for the hormonal treatment subgroup : Primary outcome. The response (favorable versus unfavorable) to the Patient Global Impression of Improvement questionnaire at 3 months following intra-myometrial injection. A response is considered favorable when the score of Patient Global Impression of Improvement questionnaire is 1 or 2. Patient Global Impression of Improvement questionnaire is self-assessment scale ranging from 1 (Very much improved) to 7 (Very much worsened).

Exploratory analysis for the hormonal treatment subgroup : procedural pain. Pain intensity during the procedure assessed via numerical rating scale. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Exploratory analysis for the hormonal treatment subgroup : adverse events.

For the exploratory analysis of subgroups of patients with and without amenorrhea : Primary outcome. The response (favorable versus unfavorable) to the Patient Global Impression of Improvement questionnaire at 3 months following intra-myometrial injection. A response is considered favorable when the score of Patient Global Impression of Improvement questionnaire is 1 or 2. Patient Global Impression of Improvement questionnaire is self-assessment scale ranging from 1 (Very much improved) to 7 (Very much worsened).

For the exploratory analysis of subgroups of patients with and without amenorrhea: Average intensity of dysmenorrhea evaluated using a numerical rating scale during the last menstrual cycle before injection, then at 3 and 6 months. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Exploratory analysis for the hormonal treatment subgroup : emergency visits.

For the exploratory analysis of subgroups of patients with and without amenorrhea : Maximum intensity of dysmenorrhea evaluated using a numerical rating scale during the last menstrual cycle before injection, then at 3 and 6 months. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

For the exploratory analysis of subgroups of patients with and without amenorrhea : Duration (in days) of dysmenorrhea during the last menstrual cycle before injection, then at 3 and 6 months.

For the exploratory analysis of subgroups of patients with and without amenorrhea : Average intensity of non-menstrual pelvic pain evaluated using an numerical rating scale before injection, then at 1, 3, and 6 months. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

For the exploratory analysis of subgroups of patients with and without amenorrhea : Maximum intensity of non-menstrual pelvic pain evaluated using an numerical rating scale before injection, then at 1, 3, and 6 months. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

For the exploratory analysis of subgroups of patients with and without amenorrhea : Duration of non-menstrual pelvic pain (in days) evaluated before injection, then at 1, 3, and 6 months

For the exploratory analysis of subgroups of patients with and without amenorrhea : Average intensity of pain during the most recent sexual intercourse, evaluated using an numerical rating scale before injection, then at 1, 3, and 6 months. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

For the exploratory analysis of subgroups of patients with and without amenorrhea : Sexual function assessed using the Female Sexual Function Index before injection, and then at 1, 3, and 6 months. The Female Sexual Function Index consists of 19 items assessing six dimensions of female sexual function (desire, arousal, pain, lubrication, satisfaction, orgasm). The total score ranges from 2 to 36, with sexual dysfunction defined as a score below 23.

For the exploratory analysis of subgroups of patients with and without amenorrhea : Central sensitization to pain assessed using the Convergences PP score, before injection and at 3 months. The total Convergence PP score ranges from 0 to 10, with pelvic hypersensitivity defined as a score greater than or equal to 5.

For the exploratory analysis of subgroups of patients with and without amenorrhea : Heavy menstrual bleeding assessed using the Higham score during the last menstrual period, before injection, and at 3 and 6 months. The Higham score is an objective assessment score of menstrual blood loss. Each day of menstruation, the patiente counts the number of pads or tampons used, referring to a visual chart. A score above 100 points corresponds to a blood loss of 80 mL, which defines menorrhagia.

For the exploratory analysis of subgroups of patients with and without amenorrhea : General quality of life assessed using the The Short Form (36) Health Survey before injection, and at 1, 3, and 6 months. The questionnaire The Short Form (36) Health Survey is a multidimensional, generic scale, meaning it assesses health status regardless of the underlying condition, gender, age, or treatment. Its 36 items evaluate 8 domains: physical activity, physical role limitations, bodily pain, perceived health, vitality, social functioning, emotional state, and mental health. Each item is scored from 0 (lowest score) to 100 (highest score). At the end, a score for each SF-36 dimension is calculated based on the corresponding items, ranging from 0 (poor quality of life) to 100 (best quality of life).

For the exploratory analysis of subgroups of patients with and without amenorrhea : Disease-specific quality of life assessed using the Endometriosis Health Profile EHP-5 questionnaire (it is the short version of Endometriosis Health Profile EHP-30) before injection, and at 1, 3, and 6 months. This short questionnaire includes only 11 out of 30 questions, to which patients must respond with Always, Often, Sometimes, Rarely, or Never. This questionnaire ranging from 0 (the best health status) to 44 (the worst health status).

For the exploratory analysis of subgroups of patients with and without amenorrhea : Number of days of school or work absenteeism in the past month, assessed before injection and at 1, 3, and 6 months.

For the exploratory analysis of subgroups of patients with and without amenorrhea : Anxiety assessed using the State and Tait Anxiety Inventoy scale-Y before injection and at 3 months. This State and Tait Anxiety Inventoy scale-Y includes two distinct scales for assessing state anxiety (STAI Form Y-A) and trait anxiety (STAI Form Y-B). The Trait Anxiety scale consists of 20 items and assesses the individual's general tendency to experience anxiety. Scores range from 21 to 77.

The State Anxiety scale also includes 20 items and measures a temporary anxious mood (stress). Scores range from 20 to 80.

For the exploratory analysis of subgroups of patients with and without amenorrhea : Depression evaluated using the Beck Depression Inventory-II before injection and at 3 months. This is a self-administered questionnaire consisting of 21 items. Each item includes 4 statements corresponding to increasing levels of symptom intensity, rated on a scale from 0 to 3. The total score is obtained by summing the scores of the 21 items. The score can be interpreted according to the following four categories: no depression (score < 10); mild depression (10 < score < 18); moderate depression (19 < score < 29); and severe depression (score > 30).

For the exploratory analysis of subgroups of patients with and without amenorrhea : Global improvement percentage (0-100%) assessed at 1, 3, and 6 months.

For the exploratory analysis of subgroups of patients with and without amenorrhea : Pain intensity during the procedure assessed via numerical rating scale. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

For the exploratory analysis of subgroups of patients with and without amenorrhea : Pain intensity at 5 minutes post-procedure, assessed via numerical rating scale

For the exploratory analysis of subgroups of patients with and without amenorrhea : Adverse events related to the injections, recorded immediately postoperatively, and at 1, 3, and 6 months.

For the exploratory analysis of subgroups of patients with and without amenorrhea : Emergency visits following the procedure, assessed at 1 month.

Exploratory analysis for the hormonal treatment subgroup : Average intensity of dysmenorrhea evaluated using a numerical rating scale during the last menstrual cycle before injection, then at 3 and 6 months. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Exploratory analysis for the hormonal treatment subgroup : Maximum intensity of dysmenorrhea evaluated using a numerical rating scale during the last menstrual cycle before injection, then at 3 and 6 months. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Exploratory analysis for the hormonal treatment subgroup : Duration (in days) of dysmenorrhea during the last menstrual cycle before injection, then at 3 and 6 months.

Exploratory analysis for the hormonal treatment subgroup : Average intensity of non-menstrual pelvic pain evaluated using an numerical rating scale before injection, then at 1, 3, and 6 months. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Exploratory analysis for the hormonal treatment subgroup : Maximum intensity of non-menstrual pelvic pain evaluated using an numerical rating scale before injection, then at 1, 3, and 6 months. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Exploratory analysis for the hormonal treatment subgroup : Duration of non-menstrual pelvic pain (in days) evaluated before injection, then at 1, 3, and 6 months

Exploratory analysis for the hormonal treatment subgroup : Average intensity of pain during the most recent sexual intercourse, evaluated using an numerical rating scale before injection, then at 1, 3, and 6 months. Numerical rating scale is self-assessment scale ranging from 0 (no pain) to 10 (maximum imaginable pain).

Exploratory analysis for the hormonal treatment subgroup : Sexual function assessed using the Female Sexual Function Index before injection, and then at 1, 3, and 6 months. The Female Sexual Function Index consists of 19 items assessing six dimensions of female sexual function (desire, arousal, pain, lubrication, satisfaction, orgasm). The total score ranges from 2 to 36, with sexual dysfunction defined as a score below 23.

Exploratory analysis for the hormonal treatment subgroup : Central sensitization to pain assessed using the Convergences PP score, before injection and at 3 months. The total Convergence PP score ranges from 0 to 10, with pelvic hypersensitivity defined as a score greater than or equal to 5.

Exploratory analysis for the hormonal treatment subgroup : Heavy menstrual bleeding assessed using the Higham score during the last menstrual period, before injection, and at 3 and 6 months. The Higham score is an objective assessment score of menstrual blood loss. Each day of menstruation, the patiente counts the number of pads or tampons used, referring to a visual chart. A score above 100 points corresponds to a blood loss of 80 mL, which defines menorrhagia.

Exploratory analysis for the hormonal treatment subgroup : General quality of life assessed using the The Short Form (36) Health Survey before injection, and at 1, 3, and 6 months. The questionnaire The Short Form (36) Health Survey is a multidimensional, generic scale, meaning it assesses health status regardless of the underlying condition, gender, age, or treatment. Its 36 items evaluate 8 domains: physical activity, physical role limitations, bodily pain, perceived health, vitality, social functioning, emotional state, and mental health. Each item is scored from 0 (lowest score) to 100 (highest score). At the end, a score for each SF-36 dimension is calculated based on the corresponding items, ranging from 0 (poor quality of life) to 100 (best quality of life).

Exploratory analysis for the hormonal treatment subgroup : Disease-specific quality of life assessed using the Endometriosis Health Profile EHP-5 questionnaire (it is the short version of Endometriosis Health Profile EHP-30) before injection, and at 1, 3, and 6 months. This short questionnaire includes only 11 out of 30 questions, to which patients must respond with Always, Often, Sometimes, Rarely, or Never. This questionnaire ranging from 0 (the best health status) to 44 (the worst health status).

Exploratory analysis for the hormonal treatment subgroup : Number of days of school or work absenteeism in the past month, assessed before injection and at 1, 3, and 6 months.

Exploratory analysis for the hormonal treatment subgroup : Anxiety assessed using the State and Tait Anxiety Inventoy scale-Y before injection and at 3 months. This State and Tait Anxiety Inventoy scale-Y includes two distinct scales for assessing state anxiety (STAI Form Y-A) and trait anxiety (STAI Form Y-B). The Trait Anxiety scale consists of 20 items and assesses the individual's general tendency to experience anxiety. Scores range from 21 to 77.

The State Anxiety scale also includes 20 items and measures a temporary anxious mood (stress). Scores range from 20 to 80.

Exploratory analysis for the hormonal treatment subgroup : Depression evaluated using the Beck Depression Inventory-II before injection and at 3 months. This is a self-administered questionnaire consisting of 21 items. Each item includes 4 statements corresponding to increasing levels of symptom intensity, rated on a scale from 0 to 3. The total score is obtained by summing the scores of the 21 items. The score can be interpreted according to the following four categories: no depression (score < 10); mild depression (10 < score < 18); moderate depression (19 < score < 29); and severe depression (score > 30).

Exploratory analysis for the hormonal treatment subgroup : Global improvement percentage (0-100%) assessed at 1, 3, and 6 months.

Exploratory analysis for the hormonal treatment subgroup : Pain intensity at 5 minutes post-procedure, assessed via numerical rating scale