Recurrent miscarriage: causes, workup, and what happens next

When pregnancy loss happens more than once

A miscarriage is one of the most distressing experiences a person or couple can face. When it happens a second time, the grief compounds with fear — and questions become urgent: why is this happening? Is something wrong? Will it happen again?

Recurrent pregnancy loss (RPL) — now defined as two or more losses — is more common than many people realise, affecting approximately 1–3% of couples attempting to conceive. It is important to know from the outset that despite thorough investigation, roughly half of all RPL cases remain unexplained after a complete workup. And, importantly, even without a clear cause, most couples with unexplained recurrent losses go on to have a successful pregnancy with appropriate support and early monitoring.

This article outlines the current Australian approach to recurrent miscarriage — what is investigated, what treatable causes look like, and what the evidence says about the next pregnancy.

A. Core clinical — the AU general-practice framework

Redefining when investigation should begin

The old threshold of three losses before investigation was based on statistical probability — two consecutive losses could reasonably occur by chance. But both RANZCOG’s 2024 recurrent miscarriage statement and the ESHRE Recurrent Pregnancy Loss Guideline 2023 now set the threshold at two losses, including biochemical pregnancies confirmed by blood test. Earlier investigation means earlier identification of treatable causes and earlier emotional validation for the couple.

What the GP-led first-pass workup involves

The initial workup can be largely arranged by the GP. It combines blood tests, imaging, and chromosome analysis for both partners.

Blood tests for the person who was pregnant:

• Antiphospholipid syndrome (APS) panel — lupus anticoagulant, anti-cardiolipin IgG/IgM (aCL), and anti-β2-glycoprotein I. Two positive results, at least 12 weeks apart, are required for diagnosis.
• TSH and thyroid peroxidase antibodies (TPO Ab) — thyroid dysfunction, particularly with positive TPO antibodies, is associated with miscarriage. The preconception TSH target where TPO antibodies are present is 0.5–2.5 mIU/L.
• HbA1c — to screen for undiagnosed or poorly controlled diabetes, which impairs early placental function.
• Vitamin D — routine preconception repletion of deficiency.
• FBC, ferritin, B12, folate, kidney and liver function — baseline screen; correct any deficiencies before the next pregnancy.
• Prolactin, LH, FSH, oestradiol, AMH — where there is irregular menstruation, suspected PCOS, or older age with reduced ovarian reserve.

Parental chromosome analysis (karyotype): Both partners have a peripheral blood karyotype arranged. This identifies balanced chromosomal translocations or inversions, which account for approximately 2–5% of recurrent miscarriage and are important for genetic counselling and family planning decisions. The GP can request this under MBS item 73289, which is Medicare-rebatable for the recurrent miscarriage indication.

Uterine cavity assessment: A pelvic transvaginal ultrasound (ideally 3D) evaluates uterine shape and the cavity. If the ultrasound is inconclusive, saline-infused sonography (sonohysterography) or hysterosalpingogram (HSG) provides better detail. These investigations look for a uterine septum, submucosal fibroids, intrauterine adhesions (Asherman’s syndrome), and major uterine anomalies.

What is NOT recommended in routine first-pass workup

ESHRE 2023 specifically recommends against several tests that are sometimes requested but lack evidence:

• Routine inherited thrombophilia panel (factor V Leiden, prothrombin gene mutation, protein C and S, antithrombin) — not recommended unless there is a personal or strong family history of venous thromboembolism, because treatment with blood thinners has not been shown in randomised trials to improve live birth rates in RPL without APS.
• NK cell, Th1/Th2 cytokine, or reproductive immunology panels — not validated; not recommended.
• TORCH serology (toxoplasma, rubella, CMV, herpes) — only if there are specific clinical indications.
• Empirical progesterone, IVIG, corticosteroids, or intralipid — outside controlled trials, these are not recommended for unselected RPL.

Treating identified causes

Antiphospholipid syndrome — the most important treatable cause. Treatment is low-dose aspirin 100 mg daily plus enoxaparin 40 mg subcutaneous injection daily, started from the time of positive pregnancy test and continued until 6 weeks postpartum. The Empson Cochrane 2005 review demonstrated combination therapy was superior to aspirin alone, achieving live-birth rates of approximately 70–80% compared with less than 30% untreated. Referral to obstetric medicine or a maternal-fetal medicine specialist is recommended once APS is confirmed.

Thyroid dysfunction — levothyroxine is prescribed to maintain TSH within target. The target is 0.5–2.5 mIU/L during pregnancy where TPO antibodies are positive, and below 4 mIU/L if TPO antibodies are negative.

Glycaemic optimisation — HbA1c below 6.5% is the pre-pregnancy target in known diabetes. Referral to endocrinology or a diabetes-in-pregnancy clinic is appropriate where needed.

Uterine septum — historically, hysteroscopic surgery to remove the fibrous septum was standard. However, the TRUST randomised controlled trial (Rikken, Human Reproduction Open 2021) did not demonstrate a clear benefit in live birth rates compared with expectant management. This remains a shared decision with a subspecialist for significant septae or where no other cause has been found.

Asherman’s syndrome and submucosal fibroids — hysteroscopic correction remains recommended, with generally good outcomes for restoring cavity architecture.

Balanced translocation in either partner — referral to clinical genetics is indicated. Options include natural conception with prenatal testing in the next pregnancy, IVF with preimplantation genetic testing for structural rearrangements (PGT-SR), or donor gametes.

Idiopathic RPL — when no cause is found, the evidence still supports a positive approach. A programme of early antenatal review — weekly to fortnightly reassurance ultrasound scans through the first trimester, with the same clinician where possible — is associated with live-birth rates of approximately 70–80%, per the landmark Stray-Pedersen study (1984) and Clifford et al. (1997). This is often called the “Tender Loving Care” (TLC) approach.

B. The evidence on progesterone in recurrent miscarriage

Why the evidence needs careful reading

Progesterone supplementation in recurrent pregnancy loss is one of the most discussed topics in reproductive medicine — and also one of the most nuanced. The evidence points clearly in two different directions depending on the clinical scenario.

PROMISE trial (NEJM 2015): In women with unexplained recurrent miscarriage who were not currently bleeding, micronised vaginal progesterone did not improve live birth rates compared with placebo. Progesterone is therefore not recommended for unselected RPL.

PRISM trial (NEJM 2019): In a different population — women with first-trimester bleeding and at least one previous miscarriage — vaginal progesterone 400 mg twice daily until 16 weeks significantly increased live birth rates. The benefit was most pronounced in women with three or more previous losses and active bleeding (number-needed-to-treat approximately 14 in this subgroup).

The practical implication: progesterone is a selective treatment for women who are currently pregnant, experiencing first-trimester bleeding, and have had prior pregnancy loss — not a routine prevention for all women with recurrent miscarriage who are trying again.

Hydroxychloroquine as an emerging option in APS

For women with confirmed APS, hydroxychloroquine is emerging as a potentially useful adjunct to aspirin and enoxaparin. Early trial data including the HYPATIA pilot study suggest improved live-birth outcomes, though the evidence is not yet sufficient for routine recommendation. This remains a specialist decision.

C. Preconception care and preparing for the next pregnancy

The preconception checklist

Before attempting the next pregnancy, the following should ideally be confirmed or optimised:

• Any identified cause treated — APS regimen ready to start immediately on positive pregnancy test; thyroid or glucose optimised.
• Folate 0.5 mg daily started at least one month before conception; 5 mg daily if BMI above 30, pre-existing diabetes, anti-epileptic medication use, or prior neural tube defect.
• Iodine 150 µg daily for brain development support.
• Smoking cessation for both partners — smoking increases miscarriage risk and causes DNA damage to sperm.
• Alcohol cessation for both partners — alcohol is embryotoxic.
• BMI optimisation to 18.5–30 where feasible — extremes of BMI independently increase miscarriage rates.
• Caffeine below 200 mg per day — there is a modest signal that higher intakes are associated with increased risk.
• Rubella and varicella immunity — check serology if not previously confirmed.
• Cervical screening — ensure up to date.
• Early antenatal booking plan — arrange to be seen early, ideally at 7–8 weeks, with reassurance scans planned.

Products of conception analysis

If surgical management of a future loss is required, chromosome microarray analysis of the products of conception provides the most clinically useful information — distinguishing an aneuploid (chromosomally abnormal) loss (most likely a sporadic event with lower recurrence risk) from a euploid (chromosomally normal) loss (higher likelihood of a maternal or uterine cause requiring further investigation).

D. Australian operations

MBS pathways for the workup

The APS panel, TSH and TPO antibodies, HbA1c, vitamin D, and full blood count are all Medicare-rebatable through standard GP pathology requests. Parental karyotype (MBS item 73289) is Medicare-rebatable under the recurrent miscarriage indication. Pelvic ultrasound (MBS items 55700/55703), saline-infused sonography (item range around 55718), and hysterosalpingogram (item 59103) are Medicare-rebatable through specialist or GP referral.

Pregnancy Support Counselling (MBS items 4001, 4003, 4005) provides three subsidised counselling sessions per pregnancy and can be used in the context of recurrent loss and pregnancy anxiety. Mental Health Treatment Plan (MBS items 2715/2717) supports referral to psychology under Better Access (items 80000–80020) for comorbid anxiety, depression, or grief.

The GPCCMP (MBS items 965/967) supports allied health referral when a comorbid condition — diabetes, thyroid disease, or autoimmune disease — forms part of the clinical picture.

PBS and medication costs

Levothyroxine, low-dose aspirin (100 mg), and folate are PBS General Schedule or available over the counter. Enoxaparin (Clexane) 40 mg for APS-related recurrent miscarriage is available on PBS under the VTE prophylaxis / maternity indication — confirm the prescribing pathway with the specialist at the time of initiation. Vaginal micronised progesterone (Crinone, Endometrin) is not PBS-listed and is supplied privately through pharmacies or fertility clinics, with out-of-pocket costs typically $80–$200 per month.

Specialist referral pathway

Situation	Refer to	Timing
Confirmed APS	Obstetric medicine or maternal-fetal medicine	Routine — within 4–6 weeks
Balanced parental translocation	Clinical genetics + fertility specialist	Soon
Recurrent second-trimester losses	Maternal-fetal medicine	Soon
Confirmed uterine anomaly	Gynaecology / fertility specialist (AGES)	Routine
Complex or unexplained after full workup	Reproductive medicine / IVF service	Routine

E. Special populations

Older maternal age

Miscarriage risk rises substantially with age: approximately 10% at age 25–29, 20% at 35, 40% at 40, and 80% at 45. The dominant cause of age-related miscarriage is embryonic aneuploidy — chromosomal abnormalities in the egg increase markedly from the mid-thirties onwards. This means that in older women with recurrent miscarriage, a higher proportion of losses are chromosomally abnormal (and therefore less likely to be due to a maternal systemic cause). IVF with preimplantation genetic testing for aneuploidy (PGT-A) is a specialist option for selected couples, though the evidence for improving live birth rates per started cycle is mixed (STAR trial, Fertil Steril 2019), and it is not Medicare-funded.

Same-sex couples and single parents using donor gametes or surrogacy

Recurrent miscarriage in this context requires exactly the same workup as in any other couple. The emotional complexity may be heightened by the cost and logistical investment in the fertility treatment itself. MHCP-funded psychology and peer support through organisations such as SANDS Australia and Pink Elephants are appropriate referrals.

Aboriginal and Torres Strait Islander families

Pregnancy loss is recognised in Aboriginal and Torres Strait Islander culture through grief traditions including Sorry Business. Cultural safety — acknowledging the specific cultural and spiritual significance of the loss, involving family where appropriate, and connecting with Aboriginal Health Workers — is fundamental to care. The ATSI Health Assessment (MBS 715) provides an annual structured opportunity to discuss reproductive history, preconception health, and loss.

Mental health after recurrent loss

Recurrent pregnancy loss is associated with approximately double the risk of clinically significant anxiety and depression. These are not merely understandable emotional reactions — they are clinical conditions that warrant active management. Partner mental health is often neglected in clinical assessments. Routine screening with validated tools (PHQ-9, GAD-7) at each consultation, MHCP referral, and direct referral to SANDS, Pink Elephants, PANDA, COPE, and the Gidget Foundation should be offered proactively to both partners.

When to escalate

Refer urgently or on the same day for:

• Suspected ectopic pregnancy in any current pregnancy loss
• Haemodynamic instability during a loss
• Septic miscarriage (fever, severe pain, offensive discharge after a loss)
• Psychiatric crisis or suicidality

Refer soon (within 4–6 weeks) for:

• Confirmed APS (two positive tests at 12 weeks) — to obstetric medicine
• Balanced chromosomal translocation in either partner — to clinical genetics
• Recurrent second-trimester losses — to maternal-fetal medicine
• Complex uterine anomaly — to gynaecology

What this article is and is not

This is general health information drawn from current Australian guidelines — RANZCOG, eTG, RACGP, ESHRE, Cochrane evidence — and is intended to help patients and families understand recurrent pregnancy loss. It is not personal medical advice and does not create a doctor–patient relationship. Decisions about investigation, treatment, and the next pregnancy are made with your own GP and specialist team.

For support: SANDS Australia 1300 308 307 (24/7 peer support); Pink Elephants Support Network; PANDA 1300 726 306; COPE — Centre of Perinatal Excellence; Gidget Foundation. For crisis support: Lifeline 13 11 14.

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Sources cited

1. RANZCOG — Recurrent miscarriage statement 2024
2. ESHRE — Recurrent Pregnancy Loss Guideline 2023
3. Therapeutic Guidelines — Obstetrics and Gynaecology
4. RACGP — Pregnancy Care Guidelines
5. Empson et al. — Cochrane review of anti-thrombotic therapy for APS (2005)
6. Coomarasamy et al. — PROMISE trial (NEJM 2015)
7. Coomarasamy et al. — PRISM trial (NEJM 2019)
8. Stray-Pedersen — TLC in idiopathic RPL (Br J Obstet Gynaecol 1984)
9. Bates — ASH 2018 guidelines for VTE in pregnancy
10. SANDS Australia
11. Pink Elephants Support Network
12. PANDA — Perinatal anxiety and depression support
13. COPE — Centre of Perinatal Excellence
14. Gidget Foundation
15. HealthDirect — Pregnancy loss