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.
Age 18 - 38 years old
Endometriosis AAGL stage III-IV
Referred or eligible for ART-treatment such as IVF or ICSI, independent of infertility diagnosis (28) (including sperm donation cycles for social reasons) and/or infertility due to dyspareunia/dysmenorrhea caused by endometriosis
Body mass index 18-35 kg/m2
Previous surgery for endometriosis except diagnostic laparoscopy.
Previous IVF/ICSI-cycles (including prior fertility preservation cycles)
Hemato- and/or hydrosalpinx
Clear indication for surgery such as ureteral stenosis or intestinal sub-occlusive symptoms
Parallel
Endometriosis surgery
Procedure/SurgeryEndometriosis surgery followed by ART
Cumulative live-birth rate (CLBR)
CLBR is defined as any live births from first treatment until end of follow up (three years from first ART treatment or surgery or drop out from the study, whichever comes first).
Cumulative Pregnancy Rate (CPR)
Cumulative Pregnancy Rate (CPR) is defined as all pregnancies confirmed with ultrasound, from first treatment (surgery or ART) until three years of follow up.
Time to pregnancy and live birth
Time to pregnancy is defined as time from first treatment (surgery or ART) to first pregnancy confirmed with ultrasound. Time to live birth defined as time from first treatment (surgery or ART) to first livebirth.
Spontaneous Pregnancy Rate
Spontaneous pregnancy rate is defined as any spontaneous pregnancy occurring between first treatment and end of follow-up.
Miscarriage rate and/or extrauterine pregnancies
Miscarriage rate defined as frequency and proportion of spontaneous loss of any clinical and biochemical pregnancy before week 22 and/or extrauterine pregnancy defined as a pregnancy not located in the uterine cavity, occurring between first treatment and end of follow-up.
P-progesterone levels on the day of frozen embryo transfer in HRT cycle
P-progesterone levels on the day of frozen embryo transfer in HRT cycle. Serum progesterone concentration (ng/mL).
Adenomyosis
The presence of suspected adenomyosis, on ultrasound and/or MRI, will be recorded and described at baseline according to Morphological Uterus Sonographic Assessment (MUSA) (26, 27). The presence of adenomyosis will not affect allocation but will be used at the end of the study in the interpretation of the findings, as a sub-group analysis.
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Karolinska Institutet
Lead sponsor
Region Stockholm
Collaborator
The Swedish Medical Association
Collaborator
Forte
Collaborator
Västra Götalandsregionen
Collaborator
