First Line Surgery or First Line Fertility Treatment Using Assisted Reproductive Technologies in Patients With Advanced Endometriosis
brief summary
Endometriosis is a chronic disease affecting approximately 10% of women of reproductive age. It is strongly associated with pelvic pain and infertility. Women with advanced stages of the disease (stage III-IV) have markedly reduced fertility compared with the general population. A Swedish study has shown that about 22% of women undergoing treatments with assisted reproductive technologies (ART), such as in vitro fertilization (IVF), are affected by endometriosis. The optimal management of women with advanced endometriosis and infertility remains uncertain. Some clinicians advocate proceeding directly to IVF, while others suggest surgical removal of endometriosis lesions prior to IVF in order to improve the chances of pregnancy. Currently, evidence is limited to a small number of observational studies. Two observational studies and one meta-analysis have suggested that surgery before IVF in women with deep endometriosis may increase both pregnancy and live birth rates compared with IVF alone. However, no randomized controlled trial (RCT) has yet been conducted to answer this important clinical question. This study will be the first national multicenter randomized controlled trial to compare surgery followed by IVF with IVF alone in women with advanced endometriosis and infertility. All Swedish centers for highly specialized endometriosis surgery and fertility treatment will participate. Eligible participants are women under 39 years of age with stage III-IV endometriosis who seek fertility treatment. Participants will be randomized in a 1:1 ratio to one of two groups: * Surgery prior to IVF (laparoscopic excision of endometriosis lesions, followed by IVF). * Direct IVF without prior surgery. The primary outcome is the cumulative live birth rate within three years of randomization and initiation of the allocated treatment. Secondary outcomes include pregnancy rates, time to pregnancy, treatment-related complications, patient-reported quality of life, and cost-effectiveness. Our hypothesis is that surgery before IVF will lead to a higher cumulative live birth rate compared with IVF without prior surgery in women with advanced endometriosis. The results of this trial are expected to have significant impact on clinical practice and international guidelines. Regardless of outcome, the study will provide robust evidence to guide treatment strategies, improve the care of women with advanced endometriosis and infertility, and potentially reduce healthcare costs by identifying the most effective pathway to achieving pregnancy.
detailed description
WHY THIS TRIAL IS NEEDED
BACKGROUND
Endometriosis Endometriosis is a prevalent condition affecting 10% of female population of reproductive age, leading to pain and sub-fertility. An earlier systematic literature reviews and meta-analysis suggests that women with advanced endometriosis (revised American Society for Reproductive Medicine classification of endometriosis (rASRM) stage III-IV) have a lower likelihood of achieving clinical pregnancy/live birth compared to women without endometriosis, while this difference has not been observed for mild disease (stage I-II).
Gynaecological Ultrasound and staging The prevalence of endometrioma and deep endometriosis found through systematic transvaginal ultrasound on women referred for ART treatment in Sweden has been estimated at 21.8%. Additionally, 75.8% of those with endometriosis were unaware of their condition prior to diagnosis. In recent years, two staging systems, namely the American Association of Gynecologic Laparoscopists (AAGL) Endometriosis classification and #ENZIAN have gained prominence owing to their accuracy when juxtaposed with surgical findings.
Surgical Treatment Women with endometriosis seem to experience pain relief after bowel surgery due to endometriosis. Consensus from the European Society of Human Reproduction and Embryology (ESHRE) indicates that surgery can be performed prior to treatment with assisted reproductive technologies (ART). Additionally, the number of spontaneous pregnancies is high after surgery on patients with deep endometriosis. Furthermore, in patients with endometriosis stage I-II or in infertile patients with endometriomas, surgery can in some cases be considered to improve fertility. However, the risk of severe complications in patients undergoing rectal surgery is up to 10% including anastomosis leakage and fistulas.
Fertility treatment An earlier meta-analysis found that the number of oocytes and fertilization rates are lower in women with endometriosis as compared to those without, although not necessarily impacting the live birth rate. Still, some previous studies have shown lower likelihood of live birth and pregnancy after in vitro fertilisation (IVF) in women with endometriosis compared to women with unexplained or tubal infertility. Even though there is some controversy when it comes to the evidence of association between endometriosis and adverse reproductive outcome after IVF, there is biological plausibility for this type of association, especially in women with advanced endometriosis (chronic inflammation affecting folliculogenesis, technical difficulties at oocyte retrieval due to endometriomas or adhesions, increased risk of pelvic infection after oocyte pick-up).
official title
First Line Surgery or First Line Fertility Treatment Using Assisted Reproductive Technologies in Patients With Advanced Endometriosis: A National Multicenter Randomized-controlled Trial