Assisted Reproductive Techniques (ART) and their possible effect on the progression of endometriosis symptoms

Study question: Do women with endometriosis experience worsening in endometriosis symptoms (quality of life, pain, bowel symptoms) when undergoing controlled ovarian stimulation (COS) during assisted reproductive techniques (ART)? Summary answer: This study did not find worsening in the abovementioned parameters during ART, which supports ART as a suitable therapeutic option for infertile women with endometriosis. What is known already: 10-25% of women with endometriosis require ART to conceive. During COS levels of estrogen increases, hence in theory increasing the risk of progression of symptoms related to endometriosis. Anaf et al. identified four cases of rapidly growing sigmoid endometriosis during ovarian stimulation resulting in cessation of ART and bowel surgery. Ten similar cases have occurred in our department since 2007. Moreover, isolated cases with severe worsening of endometriosis during COS have been reported. Study design, size, duration: Prospective cohort study carried out from February 2016 to October 2017 with a total of 177 women recruited. Participants were excluded during the study if they were lost to follow-up, or if egg retrieval was cancelled. This study is based on questionnaires containing the Endometriosis Health Profile (EHP-30), and pain and bowel habits were evaluated on the numerical rating scale (NRS). Questionnaires were administered before and after COS in one cycle of ART. Participants/materials, setting, methods: Patients < 40 years old were recruited from three fertility clinics and the endometriosis unit, Aarhus University Hospital (AUH). Depending on endometriosis diagnosis (confirmed by previous laparoscopy, transvaginal ultrasound or magnetic resonance imaging) and ART, patients were assigned one of three groups (endometriosis with or without ART, or no endometriosis undergoing ART). According to power calculations each group should include 48 women. Median and mean changes in pain and quality of life scores are reported. Main results and the role of chance: 52 women with endometriosis undergoing ART (+Endo/+ART), 50 not undergoing ART (+Endo/-ART), and 52 without endometriosis undergoing ART (-Endo/+ART), answered two questionnaires. The three groups differed significantly on all pain parameters (general and worst non-menstrual pelvic pain, dyschezia, dyspareunia, and dysuria) at baseline, women without endometriosis had a significantly better score in all EHP-30® modules (pain, control and powerlessness, social support and emotional well-being) except self-image where the groups did not differ. Bowel parameters (constipation, diarrhea, nausea, vomiting and bloating) were comparable between the groups, except that +Endo/-ART indicated worse bloating. Changes from 1st to 2nd questionnaire indicated that -Endo/+ART experienced a one NRS point greater worsening in the parameters 'tired” and 'general non-menstrual pelvic pain” compared to women with endometriosis (p=0.003, and p<0.001). Regarding worst non-menstrual pelvic pain, the median changes were 1, 2.5, and 0 for +Endo/+ART, -Endo/+ART, and +Endo/-ART, respectively (p<0.001). Women with endometriosis, undergoing ART or not, experienced a slight improvement in EHP-30® modules during ART compared to -Endo/+ART who worsened in all modules except 'self-image”. None of the three groups changed in bowel parameters except bloating where both ART groups experienced an increase of one NRS point compared to +Endo/-ART (p=0.020). Limitations, reasons for caution: Women with endometriosis were included regardless of stage, which caused disease heterogeneity. +Endo/-ART was recruited from a tertiary referral center. Hence, this group may have particularly severe endometriosis stages. In the group of women without endometriosis subclinical disease might have been present without the clinicians’ knowledge. Wider implications of the findings: Our results are in line with previous studies (Benaglia et al. and Coccia et al.) which further supports ART as a suitable therapeutic option for infertile women with endometriosis. Our two reference groups added new information by allowing differentiation between changes in parameters caused by ART and endometriosis individually. Trial registration number: The Danish Data Protection Agency: Registration number 2012-58-006). ClinicalTrials.gov: NCT02762461. Keywords: Endometriosis Artificial reproductive techniques (ART) quality of life Bowel symptoms