P-330 The impact of adenomyosis on pregnancy outcomes, from conception to birth- a systematic review and meta-analysis
Authors: Mishra I , Melo P , Easter C , Shah H , Khairy M , Rajkhowa M , Dhillon-Smith R , Coomarasamy A 
Published: July 2024

Abstract

Study question
What is the impact of adenomyosis and its phenotypes on spectrum of outcomes ranging from conception to birth?

Summary answer
Adenomyosis has a negative impact on implantation with reduced clinical pregnancy and live birth rate and increased risk of miscarriage and perinatal morbidity.

What is known already
Current evidence, including meta-analyses, on the impact of adenomyosis on reproductive outcomes is conflicting. There are data suggesting that adenomyosis has a negative impact on pregnancy outcomes whereas some studies have suggested that adenomyosis appears inert, with no impact on reproductive functions. A wide variation has been observed in the baseline population, type of Assisted Reproductive Technology (ART) stimulation protocol, number, order and type of ART cycles across the pooled observational studies. Alongside, there may be a spectrum of adenomyosis characteristics like the disease type, location, severity, and presence of coexisting endometriosis, resulting in heterogeneity and our interpretation of evidence.

Study design, size, duration
For this systematic review and meta-analysis, a comprehensive search was conducted in MEDLINE, EMBASE, CINAHL Plus, Web of Science Core Collection, Clinicaltrials.gov and WHO ICTRP from inception until January 2024 with no language restriction. Observational studies were included with participants as women with natural and/or medically assisted reproduction (MAR) conception, exposure as adenomyosis diagnosed on imaging, histology or using WHO International Classification of Disease 10th edition (ICD-10) code (N80.0) and comparator as women without adenomyosis.

Participants/materials, setting, methods
Data was included from 51 observational studies for the meta-analysis of pregnancy and obstetric outcomes. ROBINS-E tool (Risk Of Bias In Non-randomized Studies-of Exposure) was be used to assess the risk of bias. Odds ratio (OR) from individual studies were pooled using random-effects model to summarise the estimate for dichotomous outcomes with 95% confidence interval (CI) and mean differences for continuous outcomes. This was supplemented by sensitivity analyses. Clinical heterogeneity was assessed with I² statistics.

Main results and the role of chance
Women with adenomyosis had reduced odds of implantation (OR = 0.78; CI: 0.72-0.86), lower clinical pregnancy (OR = 0.87; CI: 0.82-0.92), higher miscarriage (OR = 1.51; CI: 1.44-1.58), and lower live birth (OR = 0.56; CI: 0.50-0.63) compared to those without. Both, diffuse and focal adenomyosis were associated with lower live birth (OR = 0.56; CI: 0.45-0.72; diffuse and OR = 0.56; CI: 0.45-0.70; focal). The miscarriage risk was higher in junctional zone adenomyosis (OR = 4.04; CI: 1.17-13.94) compared to outer myometrium adenomyosis. The negative impact of adenomyosis was evident in subgroups of women undergoing donor oocyte cycles (OR = 0.62; CI: 0.50-0.76; live birth and OR = 1.83; CI: 1.26-2.66; miscarriage) and first ART cycle (OR = 0.55; CI: 0.48-0.65; live birth and OR = 2.16 CI: 1.72-2.71; miscarriage). Conversely, those with euploid embryo transfer, had a higher odds of miscarriage (OR = 1.90; CI:1.05-3.43) with no significant impact on live birth (OR = 0.78; CI: 0.52-1.19). The impact continued perinatally, including pre-eclampsia (OR = 1.32; CI: 1.23-1.41), small for gestational age (OR = 1.323; CI:1.25-1.40), placenta previa (OR = 3.99, CI: 3.53-4.51), caesarean section (OR = 1.97; CI:1.89-2.05), and low Apgar scores (OR = 0.911; CI:0.88-0.96).

Limitations, reasons for caution
The inherent heterogeneity among the included observational studies was high; however, subgroup analyses for type of ART cycle, number, and order of ART cycle and by phenotype of adenomyosis had low heterogeneity. This warrants caution when interpreting pooled outcome estimates for pregnancy and obstetric outcomes across general population of women.

Wider implications of the findings
Adenomyosis has a direct and negative impact on fertility and pregnancy outcomes by virtue of impaired implantation and trophoblastic function. Hence, adenomyosis needs to be factored in when counselling women about the success of MAR cycles and requires closer monitoring in pregnancy as a high-risk pregnancy.

Trial registration number
not applicable