Obstetric outcomes after IVF/ICSI treatment in women with endometriosis and/or adenomyosis diagnosed by ultrasonography: a prospective cohort study.

Abstract

Study question: Among women pregnant after IVF/ICSI, do obstetric outcomes differ for women diagnosed with endometriosis and/or adenomyosis according to definitions by International Deep Endometriosis (IDEA) and the revised Morphological Uterus Sonographic Assessment (MUSA) groups, compared to women without the disease?

Summary answer: Women with endometriosis and/or adenomyosis have a higher risk of preterm birth, hypertensive disorders of pregnancy, placenta previa, antepartum hemorrhage, and pelvic pain, compared to women without.

What is known already: Evidence regarding the impact of endometriosis and adenomyosis on obstetric outcomes remains inconsistent, largely due to heterogeneity in study design, diagnostic methods, disease criteria, and mode of conception. Therefore, clinical guidance on antenatal management for affected women remains limited.

Study design, size, duration: This was a prospective, observational cohort study of 1035 women who underwent up to three consecutive IVF/ICSI treatments at a university hospital. Published data suggest a preterm birth risk of 8-10% after IVF/ICSI without endometriosis, with higher rates in endometriosis and adenomyosis. Assuming 10% versus 20% preterm birth, 492 women were needed for 80% power. In total, 666 women gave birth to a child between January 2019 and April 2024. Of these, 607 (91.1%) women, for which the obstetric outcomes were known, were included in the study, while the remaining 59 (8.9%) were lost to follow-up.

Participants/materials, setting, methods: Eligible for publicly funded IVF/ICSI treatments are non-smoking women aged 25 to ≤39 years, with a BMI of 18 to <30 kg/m2 and no previous children with the present partner. Women are entitled to up to three consecutive, publicly subsidized IVF/ICSI treatments, until the birth of the first child is achieved. All women underwent pretreatment ultrasound examination by an expert examiner, using the IDEA and revised MUSA definitions. Out of 607 included women, in total 144/607 (23.7%) women had endometriosis and/or adenomyosis. The primary outcome was preterm birth (delivery before completed 37 weeks gestation). Secondary outcomes included placenta previa, antepartum or postpartum hemorrhage, hypertensive disorders of pregnancy, gestational diabetes mellitus, caesarean section delivery, placental abruption, oligohydramnios, pelvic pain, and neonate small for gestational age, as well as outcomes stratified for women with different disease phenotypes. The adjusted relative risk for the different outcomes was calculated using modified Poisson regression analyses with robust error variances.

Main results and the role of chance: Preterm birth occurred in 27/144 (18.9%) women with endometriosis and/or adenomyosis compared to 53/463 (11.4%) in disease-free women, corresponding to an aRR 1.63 (95% CI, 1.06-2.49), P = 0.025. However, this was only significant for late preterm birth between gestational week 34 + 0-36 + 6 [21 (16%) vs 37 (8.0%), aRR 2.56 (95% CI, 1.26-5.21)] and not for earlier preterm birth. In addition, women with endometriosis and/or adenomyosis had an increased risk for placenta previa [13 (9.0%) vs 7 (1.5%), aRR 5.82 (95% CI, 2.32-14.6), P < 0.001], antepartum hemorrhage [17 (11.8%) vs 30 (6.5%), aRR 2.02 (95% CI, 1.19-3.41), P = 0.009], hypertensive disorders of pregnancy [19 (13.2%) vs 31 (6.7%), aRR 2.26 (95% CI, 1.29-3.97), P = 0.004] and pelvic pain [24 (16.7%) vs 40 (8.6), aRR 1.91 (95% CI, 1.21-3.01), P = 0.005] compared to disease-free women. There was a statistically non-significant tendency for an increased risk for developing oligohydramnios [10 (6.9%) vs 15 (3.3%), aRR 2.10, 95% CI, 0.98-4.48, P = 0.055] as well as delivering an SGA infant, [22 (15.3%) vs 45 (9.7%), aRR 1.58, 95% CI, 0.98-2.53, P = 0.059]. However, the risk for caesarean delivery, gestational diabetes mellitus, placental abruption, and postpartum hemorrhage was not increased.

Limitations, reasons for caution: Excluding women aged ≥40 years or with a BMI ≥ 30 kg/m2 may limit the generalizability to other populations. The presence of superficial, peritoneal endometriosis was not accounted for. The study was powered for the primary outcome preterm birth in the total cohort and may have lacked sufficient power for the secondary outcomes. The composite endometriosis and/or adenomyosis group is dominated by isolated endometriosis, with relatively few women with combined disease. Women with adenomyosis only may represent a biologically and clinically distinct subgroup. Pooling them with endometriosis could potentially dilute or mask disease-specific associations.

Wider implications of the findings: Our findings suggest that women with endometriosis and/or adenomyosis are at increased risk of common adverse pregnancy outcomes. Clinicians should recognize these risks when counseling affected women and consider tailored antenatal care.

Study funding/competing interest(s): This study was supported by regional research grants from Region Skåne, Sweden. There was no competing interest.

Trial registration number: Not applicable.