Is adenomyosis a cause of spontaneous abortion (miscarriage)?

Adenomyosis and Spontaneous Abortion: The Connection

Adenomyosis is associated with an increased risk of spontaneous abortion (miscarriage), with studies showing significantly higher miscarriage rates in women with adenomyosis compared to those without the condition. 1

Evidence for Adenomyosis as a Cause of Miscarriage

• Adenomyosis significantly increases the risk of miscarriage independent of other known risk factors such as maternal age, BMI, and embryo genetic status 1
• Studies show an adjusted miscarriage rate of 44.1% in patients with adenomyosis compared to 15.3% in those without adenomyosis (p<0.0001), with most miscarriages occurring at the early biochemical stage 1
• Adenomyosis has been identified as a potential uterine cause of recurrent miscarriage due to its persistent and often progressive nature 1
• Multiple studies have demonstrated that adenomyosis increases miscarriage rates, along with other adverse pregnancy outcomes such as preterm birth and premature rupture of membranes 2

Pathophysiological Mechanisms

• Adenomyosis impairs fertility through abnormal endometrial molecular expressions that affect implantation and early embryo development 3
• The condition disrupts local effects of sex steroid and pituitary hormones, immune responses, inflammatory factors, and neuroangiogenic mediators 3
• All proposed pathogenetic mechanisms of adenomyosis reduce endometrial receptivity and alter the adhesion molecule expression necessary for embryo implantation 3
• These mechanisms collectively contribute to lower pregnancy rates, higher miscarriage rates, and adverse obstetric outcomes 3

Risk Factors and Associated Conditions

• Women who are multiparous, have leiomyoma (fibroids), a previous history of abortion, and normal body mass index are at increased risk for developing adenomyosis 4
• There is a significant positive correlation between adenomyosis and the presence of leiomyoma (p<0.0001), history of previous abortion (p<0.0001), and history of previous pregnancy (p=0.0002) 4
• Adenomyosis often coexists with other gynecological conditions, which can compound fertility issues 5

Treatment Approaches for Fertility Preservation

• GnRH agonist pre-treatment significantly reduces miscarriage risk in adenomyosis patients, with miscarriage rates of 35.7% in treated patients compared to 82.4% in untreated patients (p=0.0089) 1
• For patients undergoing assisted reproductive technology, a long GnRH agonist protocol shows better outcomes compared to short stimulation protocols, with lower miscarriage rates (18.5% vs 31.1%, p<0.0001) 6
• Surgical treatments for adenomyosis have shown limited success for spontaneous pregnancies (18.2% pregnancy rate), but when combined with GnRH analogues for 24 weeks after surgery, pregnancy rates improve significantly (40.7% vs 15.0%, p=0.002) 6
• Uterine Artery Embolization (UAE) has shown early success in controlling symptoms of bleeding with adenomyosis, but long-term durability is questionable with recurrence rates of approximately 40-50% at 2 years 5

Clinical Implications and Management

• Screening for adenomyosis is recommended for all women undergoing fertility treatment, especially those with a history of miscarriage 1
• Women with adenomyosis require specialized prenatal management in a tertiary center due to increased risk of obstetrical complications 2
• For women with adenomyosis and fibroids who fail conservative measures and desire uterus-preserving therapy, UAE can improve quality of life and symptom scores, especially when fibroids predominate 5
• Progestin IUDs and oral GnRH antagonist combinations have shown effectiveness in treating heavy menstrual bleeding associated with adenomyosis, though these therapies will not address bulk symptoms 5

Caveats and Pitfalls

• The relationship between adenomyosis and miscarriage is complex and may be influenced by other factors such as age, BMI, and coexisting conditions 1
• The extent of adenomyosis (focal or diffuse disease) may modify miscarriage risk, but current studies have limited sample sizes to fully analyze this aspect 1
• While UAE can be considered for symptom management in adenomyosis, it should not be the first-line choice for women seeking pregnancy due to increased risks of miscarriage (35%), cesarean sections (66%), and postpartum hemorrhage (13.9%) 5, 7
• Evidence regarding fertility outcomes after various treatments for adenomyosis is still limited, highlighting the need for high-quality prospective randomized controlled trials 1, 6