Recurrent pregnancy loss - clinical fact sheet and MCQ

Overview

Recurrent miscarriage, also referred to as recurrent pregnancy loss (RPL), is defined as the loss of two or more confirmed intrauterine pregnancies of up to 20 weeks’ gestation. This definition includes both consecutive and non-consecutive losses, provided each loss is confirmed. RPL affects approximately 1–4% of couples, with the risk increasing with maternal age. Though the causes remain unexplained in up to 50% of cases, a range of anatomical, genetic, endocrine, immunological and thrombophilic factors may be implicated. Each pregnancy loss can have significant psychological and emotional consequences, underlining the importance of compassionate and comprehensive care in general practice.

Diagnosis of recurrent miscarriage

1. Risk factors

Known or suspected contributors to RPL include:

• increasing maternal and paternal age

• high body mass index

• smoking

• alcohol consumption

• uncontrolled diabetes

• antiphospholipid syndrome (APS)

• thyroid dysfunction

• congenital uterine anomalies

• genetic abnormalities

The preconception period is the optimal time for assessing and modifying risk factors.

2. Assessments and investigations

Evaluation is recommended after two or more losses. The following investigations should be considered:

• Screening tests:

• antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, and β2 glycoprotein I antibodies)

• parental karyotyping

• thyroid function tests

• pelvic ultrasound (to assess uterine anatomy)

• full blood count and screening for diabetes if clinically indicated

Table 1. Screening tests in recurrent pregnancy loss

Clinicians should discuss with patients the potential benefits and limitations of these tests, including the emotional impact of inconclusive results.

• Cytogenetic analysis of pregnancy tissue is not routinely recommended due to low impact on future clinical decisions

• Genetic testing:

• for couples with structural chromosomal rearrangements (eg balanced translocations), options include natural conception or IVF with preimplantation genetic testing for structural rearrangements (PGT-SR)

• there is insufficient evidence supporting IVF with preimplantation genetic testing for aneuploidy (PGT-A) in cases without a known genetic cause

• Uterine anomalies:

• routine surgical correction, such as septum resection or resection of congenital malformations (eg arcuate, unicornuate uterus), is not recommended

• surgical options (eg hysteroscopic adhesiolysis, polypectomy) should only be considered on a case-by-case basis, weighing symptoms and patient preferences

• Thyroid dysfunction:

• if iodine deficiency is excluded, treat overt hypothyroidism with levothyroxine

• do not offer levothyroxine for subclinical hypothyroidism or isolated thyroid autoantibodies unless TSH is persistently elevated (>2.5 mIU/L); monitor thyroid function early in pregnancy if untreated

3. Red flags and referral triggers for recurrent pregnancy loss

• suspected APS

• recurrent second trimester losses

• suspected uterine anomalies unresolvable via primary care imaging

• positive parental karyotypes

• repeated miscarriage despite normal investigations

These situations warrant referral to a gynaecologist or a specialised RPL clinic where available.

Management of recurrent pregnancy loss in primary practice

1. Supportive care and monitoring

Psychological support is fundamental. Acknowledgement of the emotional toll and referral to counselling services should be offered routinely. While specific evidence for recurrent miscarriage clinics is limited, regular ultrasound monitoring and early pregnancy support may improve outcomes and patient satisfaction.

2. Pharmacological treatments

• Antiphospholipid syndrome:

• offer low-dose aspirin (75–150 mg/day), either prior to pregnancy or from positive pregnancy test, until at least 34 weeks (cease prior to birth) AND

• low molecular weight heparin from positive pregnancy test until at least 34 weeks (cease prior to birth)

• this combination improves live birth rates in women with confirmed APS compared to aspirin alone

• note: Therapeutic Guidelines recommendation: ‘For patients with a history of obstetric antiphospholipid syndrome, LMW heparin and low-dose aspirin are recommended for the duration of the pregnancy and for 6 to 12 weeks postpartum.’

• Progesterone supplementation for recurrent miscarriage:

• only recommended for women with RPL who present with early pregnancy bleeding: vaginal micronised progesterone 400 mg twice daily until 16 weeks’ gestation

• Levothyroxine:

• offer to women with overt hypothyroidism prior to pregnancy 

• do not offer for subclinical hypothyroidism (raised TSH, normal T4) or thyroid autoantibody positivity, unless TSH is elevated (>2.5mIU/L). Repeat TSH at 7-9 weeks of pregnancy and again later if indicated.

The following are NOT recommended::

• intravenous immunoglobulin has no proven benefit and should not be routinely offered

• surgical correction of uterine anomalies (eg septum resection, caesarean scar niche resection) is not routinely recommended unless part of an individualised care plan

• routine polypectomy and fibroid resection are not supported by current evidence for improving live birth rates

3. Referral and specialist input

Referral is indicated in cases of:

• unexplained RPL despite basic investigations

• structural uterine abnormalities

• chromosomal abnormalities

• confirmed APS

• poor pregnancy outcomes despite first-line interventions

When possible, refer to a dedicated RPL clinic where tailored care, including counselling, advanced investigations, and frequent antenatal monitoring, can be coordinated.

References

1. Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG). Miscarriage, recurrent miscarriage and ectopic pregnancy (C-Gyn 38): Clinical guideline. Melbourne: RANZCOG; 2025. 203 p.
2. Therapeutic Guidelines. Antiphospholipid syndrome. 2024. (last accessed May 2025).

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