Ectopic pregnancy remains the leading cause of maternal mortality in the first trimester of pregnancy. The key failure mode in primary care is not thinking of ectopic pregnancy as a differential in a woman of reproductive age with abdominal pain and vaginal bleeding, particularly when the patient has not mentioned or does not know she is pregnant (up to 30% of women with ectopic pregnancy do not know they are pregnant at presentation). The absolute clinical rule is: any woman of reproductive age with abdominal pain or vaginal bleeding must have a pregnancy test performed. A urine pregnancy test costs £0.50 and takes 3 minutes — the failure to perform it is the most common identifiable factor in delayed ectopic diagnosis. The 'no confirmed intrauterine pregnancy' principle is critical — it is not sufficient to know the pregnancy test is positive; what matters is whether an intrauterine pregnancy has been confirmed by ultrasound. A positive pregnancy test + pelvic pain + any bleeding without confirmed IUP on USS = treat as ectopic until proved otherwise. The vaginal examination contraindication in suspected placenta praevia is a fundamental obstetric safety rule — digital vaginal examination can disrupt the placenta overlying the cervical os and trigger catastrophic, immediately life-threatening haemorrhage. This rule applies even in primary care settings where vaginal examination might seem routine: if there is any possibility of placenta praevia (third trimester bleeding, known low-lying placenta from previous scan), no digital vaginal examination should be performed before USS confirmation of placental position; speculum examination belongs in secondary care once praevia has been assessed or excluded.

The trimester-based differential is the most practical organising framework for vaginal bleeding in pregnancy because it immediately narrows the differential and determines urgency. The key principle is: all unexplained bleeding after 13 weeks needs same-day secondary-care review (NICE NG201), and any early-pregnancy bleeding without confirmed IUP is a potential ectopic until proved otherwise. Bleeding at 14–23 weeks is no less urgent than later bleeding — it includes diagnoses (late miscarriage from cervical incompetence, placenta praevia becoming symptomatic) that carry major implications for the current and future pregnancies. Vasa praevia deserves specific mention because it is rare but carries extremely high fetal mortality when undiagnosed — the rate of fetal death from vasa praevia rupture is approximately 50–75% without prior diagnosis vs less than 3% with antenatal diagnosis and planned Caesarean delivery. Risk factors for vasa praevia include: IVF conception, low-lying placenta, bilobed placenta, succenturiate lobe. The RCOG Green-top guideline on Vasa Praevia (No. 27b, 2018) does not support universal screening; targeted transvaginal colour Doppler may be considered when risk factors such as a low-lying placenta are found at the anomaly scan. GPs seeing women with these risk factors can flag them so the anomaly scan team can consider vasa praevia screening.

Serum hCG does not determine pregnancy location. For a pregnancy of unknown location, two hCG measurements are taken approximately 48 hours apart and interpreted only within an EPAU/senior clinical pathway. NICE NG126: a rise of more than 63% over 48 hours suggests a developing intrauterine pregnancy, but ectopic pregnancy is not excluded — a rising hCG does not exclude ectopic. A fall of less than 50% or a rise of less than 63% requires early pregnancy review. Do not use serum progesterone to diagnose viability or ectopic pregnancy, and do not prescribe methotrexate for a pregnancy of unknown location. Shoulder-tip pain reflects blood tracking under the diaphragm (phrenic nerve, C3–C5) — ask about it, but do not deliberately provoke it; a woman with a positive pregnancy test, abdominal pain and shoulder-tip pain needs a 999 call.

Vaginal progesterone for threatened miscarriage is one of the most important recent evidence-based developments in early pregnancy care for GPs — the PRISM trial (2019, NEJM, n=4,153) provides the evidence (the earlier PROMISE trial, in women with recurrent miscarriage but no bleeding, showed no benefit) that vaginal progesterone 400 mg BD reduces miscarriage rates in women who present with first-trimester bleeding and have an intrauterine pregnancy confirmed on USS, with the greatest benefit in women who have had one or more previous miscarriages. NICE NG126 recommends offering vaginal micronised progesterone 400 mg BD to women with bleeding in the current pregnancy who have previously had a miscarriage, once an intrauterine pregnancy is confirmed on USS (no need to wait for a heartbeat), continuing to 16 completed weeks if a fetal heartbeat is confirmed. This is a GP-initiatable treatment — the GP does not need to wait for the EPAU to prescribe. The prescription: Cyclogest 400 mg pessaries, insert vaginally BD, from confirmation of an intrauterine pregnancy to 16 completed weeks (check local formulary and SPC). Endometrial thickness is not a reliable standalone criterion for complete or incomplete miscarriage — diagnosis rests on the clinical picture and specialist ultrasound assessment, including retained products where relevant.

Anti-D immunoglobulin administration in Rh-negative women with pregnancy-associated bleeding is one of the most important preventive interventions in obstetric primary care — failure to administer anti-D when indicated is one of the most common sources of maternal harm from GP prescribing errors in obstetrics. The mechanism: if a Rh-negative mother is sensitised to fetal Rh-positive red blood cells (which can enter maternal circulation during any pregnancy-related bleeding event), she develops anti-D antibodies that in subsequent pregnancies can cross the placenta and destroy fetal red blood cells, causing haemolytic disease of the newborn (HDN) — ranging from mild jaundice to hydrops fetalis and intrauterine death. Anti-D immunoglobulin given within 72 hours of the sensitising event prevents maternal sensitisation by destroying fetal red cells before the immune response develops. NICE NG126 has been updated: up to 11+6 weeks, anti-D is not offered for ectopic pregnancy, miscarriage or threatened miscarriage; at 12+0 to 12+6 weeks it is offered with medical or surgical management and considered for heavy or recurrent bleeding; from 13 weeks, unexplained bleeding needs secondary-care review and anti-D is offered to RhD-negative patients at risk of isoimmunisation (NICE NG201), with local obstetric/transfusion protocol from 20 weeks. Every GP practice should have a clear protocol for anti-D administration in early pregnancy bleeding — including the blood group result, dose (at least 250 IU at 12+0–12+6 weeks per NG126; local protocol thereafter), route (IM deltoid), timing (within 72 hours), and documentation. Recurrent miscarriage (three or more first-trimester losses) investigation should include antiphospholipid antibody testing because APS has a proven specialist-led intervention — LMWH + low-dose aspirin in women with antiphospholipid syndrome reduces miscarriage rate from approximately 90% to approximately 30% (NNT approximately 4 for a live birth), one of the most dramatic treatment effects in reproductive medicine.

The GTD surveillance programme in the UK (managed by three specialist centres — Charing Cross Hospital, Weston Park Hospital Sheffield, and Ninewells Hospital Dundee) is one of the most successful examples of centralised cancer surveillance in the world, achieving cure rates of over 98% for all forms of gestational trophoblastic disease including choriocarcinoma. The mechanism is that beta-hCG is a uniquely sensitive and specific tumour marker for GTD — persistent or rising beta-hCG after evacuation of a molar pregnancy requires specialist assessment for persistent trophoblastic disease. The surveillance programme monitors serial urine beta-hCG samples sent by post to the specialist centre, with treatment initiated promptly if levels plateau or rise. GPs play an important role: ensuring the patient is registered with the GTD centre after molar evacuation, actioning GTD-centre correspondence, providing contraception in accordance with the specialist plan until the centre confirms surveillance is complete, avoiding pregnancy-related investigations that complicate hCG surveillance, and urgently referring heavy bleeding, infection or symptoms suggestive of metastatic disease. The methotrexate treatment protocol for ectopic pregnancy requires specific follow-up that GPs may be involved in — the key post-injection monitoring parameters are: beta-hCG on day 4 and day 7 after injection (the hCG typically rises from day 1–4 before falling — so a rising hCG on day 4 is expected and should not trigger rescue surgery), and a fall of at least 15% from day 4 to day 7 indicates treatment success. Patients must be advised to return immediately if they develop worsening pain (indicating tubal rupture even during apparently successful treatment) and to avoid NSAIDs (which reduce methotrexate renal clearance and increase toxicity).

The language used when a patient has had a miscarriage is one of the most important clinical communication skills a GP can develop — miscarriage is one of the most common and most emotionally devastating experiences that women and their partners can face, yet it is frequently trivialised or minimised by healthcare professionals. The most harmful phrases ('at least it was early,' 'you can try again,' 'it wasn't a real baby yet,' 'nature's way of dealing with abnormalities') are not medically inaccurate but are emotionally dismissive and can cause lasting psychological harm, including prolonged grief, complicated bereavement, and loss of trust in the healthcare system. The Miscarriage Association has published guidance on supportive communication that all GPs should be familiar with. The core elements are: acknowledge the loss directly and specifically, use the word 'baby' if the patient does (follow their language), allow and validate the emotional response, and avoid rushing to 'silver lining' or future-focused statements before the grief has been acknowledged. Many patients describe the GP's few words in the immediate aftermath of miscarriage as either the most healing or most harmful aspect of their entire experience. RCOG GTG 17 (2023) defines recurrent miscarriage as three or more first-trimester miscarriages, while allowing clinical discretion to investigate after two where a pathological rather than sporadic pattern is suspected.

The Valproate Pregnancy Prevention Programme (PPP) is a mandatory NHS programme that requires all women of childbearing potential prescribed sodium valproate to be on a formalised risk acknowledgement programme — this includes annual specialist review, contraception counselling, mandatory annual review by a specialist, and a signed acknowledgement of the teratogenicity risks. Valproate is associated with an approximately 11% risk of major congenital malformations (including neural tube defects) and a 30–40% risk of neurodevelopmental disorders in exposed children (MHRA). GPs who encounter a woman who is pregnant or planning pregnancy and taking valproate must immediately contact the prescribing specialist (psychiatry or neurology), as valproate is contraindicated in pregnancy unless there is absolutely no suitable alternative. If the patient is already pregnant on valproate, urgent referral to teratology services and the prescribing specialist is needed. Other teratogenic drugs that require pre-conception review: statins (all contraindicated), ACE inhibitors and ARBs (contraindicated in second/third trimester, caution in first), retinoids (isotretinoin — MHRA pregnancy prevention programme: negative pregnancy test before starting and highly effective contraception), warfarin (crosses placenta — switch to LMWH ideally before conception), mycophenolate (highly teratogenic — change to azathioprine if immunosuppression needed), thalidomide (absolute contraindication — strict pregnancy prevention programme), methotrexate (teratogenic — follow the specialist team; BSR advises stopping 1 month before conception for women, and the SPC is more cautious). Every GP should perform a medication review for teratogenic drugs when a patient of childbearing age presents, particularly after a pregnancy event.

The safety-net for ectopic pregnancy under surveillance is arguably the most critical safety message in all of early pregnancy care — women managed expectantly (falling beta-hCG) or with methotrexate can rupture their ectopic at any point during the surveillance period, even when the beta-hCG is falling. The tubal rupture can occur without warning in a woman who appeared to be responding to conservative management. Every woman managed conservatively for ectopic must have a clear written safety-net: 'If you develop any significant pelvic pain at any time, call 999 or go to A&E immediately — do not wait to see your GP or phone the EPAU.' This instruction should be documented in the clinical record at every contact during ectopic surveillance. The GTD surveillance centre contact detail (Charing Cross Hospital GTD Centre: 020 3313 5894) is worth having in the practice system — if a GP has a patient who has had a molar pregnancy and loses contact with the surveillance programme, or if a patient presents with vaginal bleeding with a history of previous molar pregnancy, the centre can be contacted directly for advice.