Recurrent Pregnancy Loss — The Workup That Pays Off

Familiar ground ~1.5 min

We know you know how common early loss is

One in four pregnancies ends in early miscarriage — and after a single loss, reassurance is the right medicine. The definitions take thirty seconds.

Recurrent pregnancy loss — the definitions

Two or more losses before 24 weeks

The ESHRE 2022 definition — this is where workup begins

RPL

They need not be consecutive

A live birth in between does not reset the count

Still counts

Biochemical losses count

A βhCG-confirmed pregnancy that never reached scan

Still counts

After one loss

No workup — reassure; the next pregnancy is usually fine

Reassure

After two

The evidence-based panel is on the table — no need to wait for three

Investigate

One loss

Reassure, support, and expect a normal next pregnancy

✓ No tests needed

Two or more — but do you know which tests actually pay off?

Every RPL test has a known yield — and half of them aren’t worth ordering

Today’s question

Every step from here answers that second question.

Why think in yields? ~2 min

Because testing smart beats testing everything

Even after a complete workup, about half of couples get no answer. Knowing each test’s expected yield prevents both the missed treatable cause and the expensive futile panel.

Every test in the RPL workup has a published chance of finding something — its yield. A handful are worth ordering for everyone; many popular ones find nothing actionable at all.

Two or more lossesthe threshold is two, not three

Order by yieldfour tests cover the routine panel

Refer with results in handany positive changes management

So here is what each test can actually be expected to find:

1 in 4

pregnancies ends in early miscarriage

population baseline

losses — the threshold to start the workup

ESHRE 2022 · RANZCOG C-Gyn 38

~60%

of fully investigated couples: no cause found

and their outlook is still good

Figure 1Expected yield of each test

Chance of a finding that changes management — confirmed, not first-draw.

POC chromosome arrayon tissue from the next loss — explains that loss

~55%

3D pelvic ultrasoundcongenital anomaly in ~13% — vs 5.5% background

~13%

TSH + TPO antibodiesTSH >4 in ~5% — the part that is treated; TPO+ ~10% ≈ background

~5%

Antiphospholipid screenfirst draw positive ~10% — persistent at 12 wks in 1–5%: the treatable cause

1–5%

Parental karyotype2–4% — and it falls sharply with maternal age

~3%

No cause foundunexplained after the full panel — plan and support

50–75%

Confirmed-finding rates: Shehata 2022 (n=1,155) · Leduc-Robert 2020 (n=1,064) · Chan 2011 meta-analysis · ranges vary by cohort

The four-test GP panel fits one request form

Lupus anticoagulant + anticardiolipin (± anti-β2GPI), TSH + TPO antibodies, and a 3D transvaginal ultrasound. Confirm any positive APS result ≥12 weeks later before labelling.

The pearl that reframes the consult

"No cause found" is not "nothing to offer"

Unexplained RPL carries a good prognosis — most couples go on to a successful pregnancy with supportive care alone. The workup’s job is to catch the treatable minority and to earn that reassurance for everyone else.

Why history changes the picture ~2.5 min

Because age and the loss pattern shift the odds — try it

Move the sliders; the counselling updates live. Colours show direction, not an individual prediction.

Your patient

Change the patient

Why did the advice change?

Honest uncertainties

Yields are cohort averages — no model predicts which couple gets an answer.
Outlook estimates come from referral-clinic cohorts and are rounded; individual counselling needs the full history.
Whether biochemical-only losses carry the same prognosis is still debated.

What to actually order ~2.5 min

Four tests to order, a few to tailor — and a list to refuse

Each line carries its yield. Tap to open the ordering detail.

Figure 2The three tiers at a glance

Order for everyoneAPS screen
TSH + TPO
3D ultrasound
POC plan

Tailor to historyParental karyotype
Sperm DNA frag.
Prolactin if symptoms

Don’t orderThrombophilia · MTHFR
NK / HLA panels
AMH for RPL

highest valueno actionable result

Antiphospholipid screen▼

confirmed 1–5%

Lupus anticoagulant + anticardiolipin IgG/IgM (reasonable to add anti-β2GPI on the same form). The one treatable serological cause — but most first positives do not persist: ~10% test positive once, only 1–5% remain positive on the mandatory ≥12-week repeat. Never label APS off a single draw. If confirmed APS: low-dose aspirin + prophylactic LMWH from positive βhCG. Not valid on warfarin/DOACs; withhold heparin 12 h pre-sample.

ESHRE Rec 15–16RANZCOG R8

TSH + TPO antibodies▼

treatable ~5%

If TSH abnormal → add free T4. Treat from TSH >4 (~5% of RPL patients). TPO antibodies are positive in ~10% — similar to background — and euthyroid TPO-positivity does not benefit from levothyroxine (ESHRE 2022 update); recheck TSH at 7–9 weeks in the next pregnancy.

ESHRE Rec 24, 47, 51RANZCOG R15–16

3D transvaginal ultrasound▼

yield ~13%

Request "TVS with 3D reconstruction" — congenital anomalies in ~13% of recurrent miscarriage vs 5.5% of all women (Chan 2011); also screens for adenomyosis. Sonohysterography is an acceptable alternative; MRI only if 3D unavailable. Anomaly found → assess renal tract. Note: septum resection is no longer routine after the Rikken RCT.

ESHRE Rec 33–38RANZCOG R8

POC array — plan it for the next loss▼

yield ~55%

Array-CGH on miscarriage tissue explains the individual loss (aneuploidy in ~55%) and spares futile maternal testing. Explanatory, not predictive — counsel before testing. Arrange the pathway now so the sample isn’t lost in the moment.

ESHRE Rec 11–12Lei 2022

Parental karyotype — tailor, don’t reflex▼

yield 2–4%

Balanced translocation in ~2–4% of RPL couples — but under 2% when she is over 39 with fewer than three losses and no family history (Franssen 2005). Best reserved for younger couples, abnormal POC, family history, or consanguinity. Abnormal → genetic counselling; natural conception outcomes remain good.

ESHRE Rec 13Franssen 2005

Sperm DNA fragmentation — selected men▼

diagnostic only

Consider in unexplained RPL, particularly with smoking, alcohol, obesity or older paternal age. Drives lifestyle counselling — no treatment has RCT support. Private-only in Australia (~$200–300).

ESHRE Rec 39–40

The refuse-politely list▼

yield ≈ 0 actionable

Inherited thrombophilia (FVL, prothrombin, protein C/S) — anticoagulation does not improve live birth; test only for independent VTE indications. MTHFR — common, benign, standard folate suffices. NK cells / HLA / cytokines — no therapeutic implication. AMH for RPL — different question entirely. Glucose/insulin, androgens, homocysteine, routine vitamin D testing, luteal-phase tests — no prognostic value; supplement vitamin D empirically and skip the blood test.

ESHRE Rec 14, 17–32, 44, 54–55RANZCOG R8 — strong against

After the results ~1.5 min

The next pregnancy needs a plan, whatever the tests show

Supportive, structured early-pregnancy care is itself associated with better outcomes — this is the part every couple receives.

Figure 3The next-pregnancy plan, week by week

What happens once the test is positive.

Positive βhCGIf confirmed APS: start aspirin ± LMWH now

6–7 weeksEarly viability scan — reassurance has value

7–9 weeksRecheck TSH if TPO-positive or prior abnormality

10–12 weeksHandover to routine antenatal care

Illustrative schedule — adapt to the individual result

Worth prescribing in words

Supportive care is an intervention

Easy access to early scans, a named contact, and an agreed plan — couples with unexplained RPL managed this way do well, with most achieving a live birth without any drug at all. Add empirical vitamin D 1000–2000 IU daily (skip the blood test), and lifestyle work for both partners.

What not to promise

No empirical aspirin, heparin or progesterone-for-all

Aspirin + LMWH helps confirmed APS — not unexplained RPL. Progesterone’s benefit is limited to women with bleeding in early pregnancy and prior losses (PRISM/PROMISE). Blanket prescriptions medicalise without helping.

How to carry it into clinic ~1 min

Remember three numbers

The quick frame

Think 2 · 4 · 1

Two losses — start, don’t wait for three

Losses need not be consecutive; biochemical counts.

Four tests with real yield

APS screen · TSH + TPO · 3D ultrasound · a POC plan for any next loss.

One written plan for the next pregnancy

Early scan access, who to call, aspirin ± LMWH only if APS confirmed.

Any positive result → refer with the result in hand. All negative → the plan and the reassurance are the treatment.

Before the third loss

The threshold is two — starting early is kindness, not over-medicine.

Before the big panel

Yield first: four tests, one form — refuse the zero-yield list politely.

Before the next positive test

Have the POC pathway and the early-pregnancy plan already written down.

Evidence anchors

Educational tool

For facilitated group teaching. Yields are cohort averages, the gauges show direction only, and nothing here replaces individualised specialist review. Check current Medicare descriptors before ordering.

Dr Yuval Fouks · Melbourne IVF — professional education use

Stay in touch any time

Questions, cases, second opinions — welcome

Happy to talk through any patient. No formal referral needed for advice.

Dr Yuval Fouks

MD · MPH · FRANZCOG

Reproductive Endocrinologist & Fertility Specialist

Phone / WhatsApp+61 493 835 221 Emailyuval.fouks@melbourneivf.com.au

Melbourne IVF36 Wellington St, Collingwood · also at Caulfield

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Professional education use