First Line Surgery or First Line Fertility Treatment Using Assisted Reproductive Technologies in Patients With Advanced Endometriosis

NCT07240363 | Recruiting DMC

• 1 other identifier: 2024-04293-01
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 4

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.

Conditions

Endometriosis; Infertility Assisted Reproductive Technology

Keywords

Endometriosis; Infertility; Surgery; ART

Outcome Measures

Primary Outcomes (1)

• 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).

  Three years from first treatment (surgery or ART treatment)

Secondary Outcomes (16)

• Cumulative Pregnancy Rate (CPR)

  From first treatment (surgery or ART) until three years of follow up

• Time to pregnancy and live birth

  Time is measured up to three years after first treatment

• Spontaneous Pregnancy Rate

  between first treatment and end of follow-up (three years)

• Miscarriage rate and/or extrauterine pregnancies

  occurring between first treatment and end of follow-up (three years)

• Number of oocytes per IVF/ICSI cycle

  At the day of oocyte retrieval for each IVF/ICSI cycle

Other Outcomes (2)

• P-progesterone levels on the day of frozen embryo transfer in HRT cycle

  On the day of frozen embryo transfer (Day 0 of transfer)

• Adenomyosis

  From first treatment ART or surgery to end of follow-up (three years)

Study Arms (2)

First-line ART

NO INTERVENTION

Women allocated in the ART arm will undergo up to three cycles of controlled ovarian stimulation (COS) followed by oocyte retrievals and embryo transfers. In Sweden, ART-treatment costs for women under the age of forty and without having children in current relationship are covered by the tax-funded healthcare system, with up to 3 IVF/ICSI treatments, given that they are considered medically meaningful, and that each stimulation is started before the woman turns 40 years of age (39). In case the treatment results in cryopreserved embryos, it is planned that they should be transferred prior to the start of any new COS. Women will be managed according to a routine clinical protocol at each reproductive unit. Stimulation protocols will be chosen individually by clinicians, taking into consideration age and ovarian reserve of each woman, as it is a standard routine in the collaborating Reproductive Units.

First-line surgery followed by ART

EXPERIMENTAL

Surgery will be performed at one of four nationally specialized centers in advanced endometriosis surgery (Södersjukhuset Stockholm, Sahlgrenska University Hospital Göteborg, Skånes University Hospital, Malmö/Lund, Uppsala University Hospital). Surgery will be conducted according to the ESHRE recommendations of surgery in endometriomas and deep endometriosis (32, 33). Surgery should be multidisciplinary when needed (colorectal surgeons and urologists). The goal of the procedure is to remove as many endometriotic lesions as possible while also minimizing negative impact on organ function, since endometriosis is a benign disease. Rectal endometriosis will be removed with rectal shaving, discoid or segmental resection depending on the size and placement of the lesion in the rectal wall. Laparoscopic cyst enucleation is considered the "golden standard". In cases where ovarian reserve is already diminished, more gentle ablation methods could be employed

Procedure: Endometriosis surgery

Interventions

Endometriosis surgery PROCEDURE

Endometriosis surgery followed by ART

First-line surgery followed by ART

Eligibility Criteria

• Age: 18 Years - 38 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• Patients who have signed an approved Informed Consent

You may not qualify if:

• 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
• Suspicion of malignancy
• Submucosal fibroids (The International Federation of Gynecology and Obstetrics (FIGO) 0-1, any size) or intramural fibroids (FIGO 2-5, \> 4 cm largest diameter of the largest myoma) (29)
• Uterine malformations (class U1-U6 according to ESHRE/ESGE-classification) (30)
• Patients with contraindications to surgery
• Patients undergoing ART with donated oocytes

Sponsors & Collaborators

• Karolinska Institutet: lead
• Region Stockholm: collaborator
• The Swedish Medical Association: collaborator
• Forte: collaborator
• Västra Götalandsregionen: collaborator

Study Sites (4)

Sodersjukhuset

Stockholm, Stockholm County, 11883, Sweden

RECRUITING

Sahlgrenska University Hospital

Gothenburg, Västra Götaland County, Sweden

NOT YET RECRUITING

Skåne university hospital, Malmö

Malmo, Sweden

NOT YET RECRUITING

Uppsala University Hospital, Uppsala

Uppsala, Sweden

NOT YET RECRUITING

Related Links

• Link to the EndoSOFT study published by the Swedish network for national clinical studies in Obstetrics and Gynecology (SNAKS)

MeSH Terms

Conditions

Endometriosis; Infertility

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Malin Brunes, MD, PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

• Anna Marklund, MD, PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 2, 2025
• First Posted: November 20, 2025
• Study Start: October 6, 2025
• Primary Completion (Estimated): September 22, 2028
• Study Completion (Estimated): September 22, 2031
• Last Updated: November 20, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 9 months following article publication Ending 36 months following article publication
• Access Criteria: Researchers who provide a methodologically sound proposal and whose proposed use of the data has been approved by an independent review committee. A data-sharing agreement will also be required. Contact: malin.brunes@regionstockholm.se

Locations

SE (4)