Skip to main content
  1. Right Decisions
  2. Maternity & Gynaecology Guidelines
  3. Gynecology
  4. Back
  5. Gynaecology guidelines
  6. Pregnancy Loss, Recurrent (708)
Announcements and latest updates

Right Decision Service newsletter: April 2024

Welcome to the Right Decision Service (RDS) newsletter for April 2024. 

Issues with RDS and Umbraco access

Tactuum has been working hard to address the issues experienced during the last week. They have identified a series of three mitigation measures and put the first of these in place on Friday 3rd May.  If this does not resolve the problems, the second mitigation will be actioned, and then the third if necessary.

Please keep a lookout for any slowing down of the system or getting locked out. Please email myself, mbuchner@tactuum.com and onivarova@tactuum.com if you experience any problems, and also please raise an urgent support ticket via the Support Portal.

Thank you for your patience and understanding while we achieve a full resolution.

Promotion and communication resources

A rotating carousel presenting some of the key RDS tools and capabilities, and an editable slideset, are now available in the Resources for RDS providers section of the Learning and Support toolkit.

Redesign and improvements to RDS

The redesign of RDS Search and Browse is still on-track for delivery by mid-June 2024. We then plan to have a 3-week user acceptance testing phase before release to live. All editors and toolkit owners on this mailing list will be invited to participate in the UAT.

The archiving and version control functionality is also progressing well and we will advise on timescales for user acceptance testing shortly.

Tactuum is also progressing with the deep linking to individual toolkits within the mobile RDS app. There are several unknowns around the time and effort required for this work, which will only become clear as the work progresses. So we need to be careful to protect budget for this purpose.

New feature requests

These have all been compiled and effort estimated. Once the redesign work is complete, these will be prioritised in line with the remaining budget. We expect this to take place around late June.

Evaluation

Many thanks to those of you completed the value and impact survey we distributed in February. Here are some key findings from the 65 responses we received.

Figure 1: Impact of RDS on direct delivery of care

Key figures

  • 93% say that RDS has improved evidence-informed practice (high impact 62%; some impact 31%)
  • 91% report that RDS has improved consistency in practice (high impact 65%, some impact 26%)
  • 85% say that RDS has improved patient safety (high impact 59%, some impact 26%)
  • Although shared decision-making tools are only a recent addition to RDS, and only represent a small proportion of the current toolset, 85% of respondents still said that RDS had delivered impact in this area (53% high impact, 32% some impact.) 92% anticipate that RDS will deliver impact on shared decision-making in future and 85% believe it will improve delivery of personalised care in future.

Figure 2 shows RDS impact to date on delivery of health and care services

 

Key figures

These data show how RDS is already contributing to NHS reform priorities and supporting delivery of more sustainable care.

Saving time and money

  • RDS clearly has a strong impact on saving practitioner time, with 90% of respondents reporting that this is the case. 65% say it has a high impact; 25% say it has some impact on time-saving.
  • It supports devolved decision-making across the multi-professional team (85% of respondents)
  • 76% of respondents confirm that it saves money compared, for example, to investing in commercial apps (54% high impact; 22% some impact.)
  • 72% believe it has impacted already on saving money and reducing waste in the way services are delivered – e.g. reducing costs of referral management, prescribing, admissions.

Quality assurance and governance

  • RDS leads are clear that RDS has improved local governance of guidelines, with 87% confirming that this is the case. (62% high impact; 25% some impact.)

Service innovation and workforce development

  • RDS is a major driver for service innovation and improvement (83% of respondents) and has impacted significantly on workforce knowledge and skills (92% of respondents – 66% high impact; 26% some impact).

New toolkits

A few examples of toolkits published to live in the last month:

Toolkits in development

Some of the toolkits the RDS team is currently working on:

  • SARCS (Sexual Assault Response Coordination Service)
  • Staffing method framework – Care Inspectorate.
  • SIGN 171 - Diabetes in pregnancy
  • SIGN 158 – British Guideline on Management of Asthma. Selected sections will be incorporated into the RDS, and complemented by a new chronic asthma pathway being developed by SIGN, British Thoracic Society and NICE.
  • Clinical pathways from NHS Fife and NHS Lanarkshire

Please contact his.decisionsupport@nhs.scot if you would like to learn more about a toolkit. The RDS team will put you in touch with the relevant toolkit lead.

Quality audit of RDS toolkits

Thanks to all of you who have responded to the retrospective quality audit survey and to the follow up questions.  We still have some following up to do, and to work with owners of a further 23 toolkits to complete responses. An interim report is being presented to the HIS Quality and Performance Committee.

Implementation projects

Eight clinical services and two public library services are undertaking tests of change to implement the Being a partner in my care app. This app aims to support patients and the public to become active participants in Realistic Medicine. It has a strong focus on personalised, person-centred care and a library of shared decision aids, as well as simple explanations and videoclips to help the public to understand the aims of Realistic Medicine.  The tests of change will inform guidance and an implementation model around wider adoption and spread of the app.

With kind regards

Right Decision Service team

Healthcare Improvement Scotland

Management of Recurrent Miscarriage (708)

Objectives

To provide guidance for the care of women experiencing recurrent pregnancy loss.

Audience

All healthcare providers in primary and secondary care within GG&C involved in the care of women experiencing Recurrent Miscarriage.

Please report any inaccuracies or issues with this guideline using our online form

Recurrent Miscarriage (RM) is defined as 3 or more first trimester miscarriages and excludes molar or ectopic pregnancies. The RCOG updated guideline does not restrict the definition to consecutive miscarriage or miscarriage with the same partner.

RM is associated with significant grief and stress. Care should be delivered sensitively and aim to meet the psychosocial needs of the couple.

Women with ≥3 first trimester miscarriages should be referred to a clinician with a special interest in RM. Referral after 2 early pregnancy losses may be considered in women ≥38 years old or when there are other risk factors identified by the Early Pregnancy Unit (EPU) or referring GP, such as history of assisted conception. Supportive care should be delivered in a dedicated recurrent miscarriage clinic.

Women with RM may present to clinic having accessed information from a variety of sources and a clear explanation of the investigation and treatments available may be helpful. It is important to allow sufficient time to obtain a detailed history and to explain that in many cases there is no cause for RM identified and often no specific risk factor contributing to the losses.

History

A full history should be obtained to identify any risk factors and will help guide management of RM: 

  • Maternal age: the risk increases with advancing maternal age, with studies suggesting that spontaneous miscarriage occurs in approximately 9% of women aged 20-24years, rising steeply after mid-30s to approximately 75% in those aged 45 years or more.
  • Advancing paternal age is also associated with RM, however to a lesser degree
  • Parity and obstetric history (primary RM is defined as no previous pregnancies beyond 24+0 weeks; secondary RM is defined as 1 ≥previous pregnancy beyond 24+0 weeks)
  • Gestation and type of pregnancy losses
  • Fertility investigations
  • Menstrual cycle and gynaecological history (including smear history, known uterine malformation, fibroids, polycystic ovarian syndrome (PCOS))
  • Body Mass Index (BMI) (a healthy BMI 19-25 is recommended)
  • Past medical and family history
  • Social history: Smoking, alcohol, caffeine intake, illicit drug use
  • Medication: including the use of folic acid/vitamin D
  • Toxin exposure: such as occupational exposure to lead, mercury, organic solvents, ionising radiation and teratogenic medications
  • Domestic abuse
  • History from Male Partners: Assessment of past medical history and lifestyle factors e.g. smoking, alcohol/drug misuse, exercise history and BMI.  Children from previous relationship.

Investigations

Investigations should be tailored to each individual. The prognosis is based on the number of preceding pregnancy losses and maternal age. Written information should be given regarding the investigations being offered and support services available. Women should be asked to wait for the results before conceiving.

  • Genetic testing
    Cytogenetic analysis of products of conception (POC) should be offered on pregnancy tissue of 3rd first trimester miscarriages (and any subsequent 1st trimester loss), and in any second trimester miscarriage.

    Currently within Scottish Genetic services, funding is only available for analysis of POC from the third or subsequent loss and testing of parental samples is only performed where an abnormality has been found in the POC. This is not in line with RCOG guidance, however, at time of writing (2024), this is a genetic test that is not currently available in Scotland.

    Issues to remember when considering pregnancy tissue genetic testing include,
    • The pregnancy losses do not need to be consecutive.
    • POC must NOT be sent in formalin, tissue should be sent dry in a universal container.
    • This test is for explanatory purposes and to detect couples carrying a balanced parental chromosomal rearrangement.
    • Around one third of samples will be reported as having “no suitable material” for genetic analysis. Suitable material is recognisable fetal tissue or chorionic villi.
    • Testing for parental karyotypes is indicated if there is an unbalanced structural chromosomal abnormality identified from analysis of the POC. This will prompt referral to Medical Genetics
    • Testing for parental karyotype may be offered by Medical Genetics if a different genetic abnormality (for example trisomy ) is identified on analysis of POC
    • If pregnancy tissue is not available at the 3rd or subsequent miscarriage (i.e. pregnancy loss managed at home) then discussion with Medical Genetics may be indicated to determine suitability for testing the parental karyotype, however this cannot currently be offered in GG&C.
    • Miscarriage of a euploid pregnancy is associated with increased risk of further miscarriage.
    • Further information can be found in the GGC guideline Fetal Tissue handling and disposal (up to and including 23+6 weeks gestation 

  • Acquired Thrombophilia - Antiphospholipid syndrome (APS)
    APS is the association between antiphospholipid antibodies (aPL antibodies) and adverse pregnancy outcome or vascular thrombosis.  Adverse pregnancy outcome is defined as 3 or more miscarriages before 10 weeks gestation, 1 or more miscarriage of a morphologically normal fetus after 10 weeks gestation, or 1 or more preterm births before 34 weeks due to placental disease.

    Issues to remember when considering acquired thrombophilia testing, include,

    • Lupus anticoagulant (LA) and Anticardiolipin antibodies (ACA IgG and IgM): may be tested no sooner than 6-8 weeks post pregnancy loss.

      Tests should be performed when women are not taking any anticoagulant or oestrogen-based medication as these can result in erroneous lupus anticoagulant results.

    • LA: reported as negative or positive

    • ACA: reported as negative (<20g/l) or positive (>20g/l)

    • All positive results should be repeated ≥12 weeks later for confirmation of the result.

    • 2 positive results at least 12 weeks apart are required to make the diagnosis of antiphospholipid syndrome.

    • A positive followed by a negative result is considered to be negative.

  • Inherited thrombophilia (factor V Leiden, prothrombin gene mutation, protein S deficiency)
    There is a weak association between inherited thrombophilia and recurrent miscarriage, therefore this is not recommended routinely.  However, testing for the presence of an inherited thrombophilia should be carried out after second trimester miscarriage.

    There is currently limited evidence that treatment changes reproductive outcomes.

    Additionally, testing should be considered to assess a women’s venous thromboembolism (VTE) risk prior to pregnancy in women with,

    • Family history of both thrombophilia and VTE
    • A first degree relative with a history of VTE which was either unprovoked  or provoked by a minor risk factor (hormone related, minor trauma or long distance travel)
    • Personal history of either an unprovoked or provoked (by a minor risk factor) VTE.

  • Endocrine testing
    Well controlled diabetes and thyroid function are not associated with an increased risk of first trimester miscarriage.

    Thyroid function tests and TPO antibodies may be considered as meta-analyses have reported an association between TPO antibodies, thyroid dysfunction and recurrent miscarriage.  The presence of TPO antibodies in euthyroid women should prompt thyroid function testing in pregnancy.

    Other endocrine assessments are not indicated unless there are clinical signs of pathology such as diabetes or hyperprolactinaemia.

  • Vitamin D
    There is an association between low levels of vitamin D and RM.  Routine testing is recommended.

  • Assessment for congenital uterine abnormality
    • Transvaginal ultrasound scan (TVS) out with pregnancy should be undertaken to assess uterine anatomy.
    • TVS has a high sensitivity and specificity to distinguish between a septate uterus and a bicorporeal uterus with a normal cervix (formerly known as a bicornuate uterus).
    • TVS may also detect the presence of adenomyosis which may be associated with pregnancy loss (not just RM).
    • MRI pelvis or hysteroscopy may be considered if there is any abnormality detected or further assessment is indicated.
    • If Mullerian malformations are diagnosed, further investigation of the kidneys and urinary tract should be offered.

Testing which is not routinely performed GG&C

  • Parental karyotype – as described previously, test if an unbalanced translocation is identified on genetics testing of POC or if advised by Medical Genetics
  • Prolactin - only test if signs/symptoms of hyperprolactinaemia (e.g. oligo/amenorrhoea)
  • Antinuclear antibodies (ANAs)
  • Inherited thrombophilia: as described above.
  • Natural Killer (NK) cells or Human Leukocyte antigen (HLA)
  • Glucose, insulin, HBA1C assessment of Polycystic ovarian syndrome (PCOS)
  • LH/FSH/testosterone unless indicated
  • Assessment of ovarian reserve (AMH)
  • Semen analysis

Treatment and Interventions to Improve Live Birth Rate (LBR) in RM

Early pregnancy ultrasound scans and engagement with an early pregnancy specialist midwife or clinician gives support and reassurance in subsequent pregnancies. Women should be aware of the referral process to the EPAU from 6 weeks if asymptomatic or earlier depending on clinical symptoms or history. Patients can self-refer to EPAU by phone or a referral can be made via Trakare by a clinician. 

Pregnancy loss counselling and support services are available via the Miscarriage Association (tel: 01924 200 799). In addition, referral to Clinical Psychology within GGC (tel: 0141 211 4532 (24532)) can be made via BadgerNet (found under MNPI) or via the GP.

For more advanced pregnancy losses, referral to the Child Bereavement Service (tel: 0141 370 4747) within the Royal Hospital for Children in Glasgow may be offered.

Advice and support should be offered on smoking cessation, regular exercise, weight management and limiting alcohol intake. Caffeine intake should be limited to less than 200 mg/day (e.g. approx. 1-2 cups of tea or instant coffee/day, energy drinks should be avoided).  In women with BMI≥ 30kg/m2  5mg folic acid daily can be offered pre-conceptually.

Genetic counselling should be offered where there is an abnormal fetal +/- parental karyotype.

Anti-thrombotic prophylaxis is not recommended, to reduce the risk of RM, for either hereditary thrombophilia or in those with unexplained RM (although it may be required to reduce the risk of VTE if risk factors exist).

  • Antiphospholipid (APL) Syndrome:

This is defined as pregnancy loss or vascular thrombosis in addition to positive LA or ACA (on two occasions, at least 12 weeks apart)

There is some evidence to support the use of Aspirin plus low molecular weight heparin (LMWH) from positive pregnancy test until at least 34 weeks gestation in those with APL syndrome and a background of RM.  If LMWH has not been commenced in early pregnancy, VTE risk assessment should be undertaken, as prophylactic LMWH may still be required for VTE prevention.

Patients with APL may already be on Aspirin out with pregnancy due to the risk of other APLS complications such as stroke. 

For those with a positive initial test for APS syndrome who  conceive before a second confirmatory test is performed, the risks and benefits of aspirin+/-LMWH in pregnancy should be discussed and treatment offered.  The second test should be performed >6weeks after pregnancy for confirmation of the result.

Women with APS treated with Aspirin and LMWH are at risk of complications in all 3 trimesters and warrant obstetric led care.

  • Hypothyroidism:

Levothyroxine should be offered to women with proven hypothyroidism and pregnancy specific levels should be used to monitor levels during pregnancy.

Subclinical hypothyroidism 

Treatment with levothyroxine should only be offered if there is true hypothyroidism (i.e. the T4 level is low). Thyroxine supplementation may be considered in those with RM and subclinical hypothyroidism (TSH >4.0ml IU/l with normal T4 levels) to ensure TSH 2.5ml IU/l but the risks must be balanced against the benefits of treatment

Thyroid antibodies

Treatment with thyroxine in women who have thyroid auto antibodies (TPO) but whom remain euthyroid does not improve the pregnancy outcome and should not be offered. These women should have TFT checked during pregnancy.

  • Vitamin D:

Women with low vitamin D, should be advised to use supplementation 10micrograms (1000 IU) daily.  This can be an over the counter preparation.

  • Progesterone:

Progestogen supplementation in the first trimester of pregnancy may reduce the rate of early pregnancy loss in those with unexplained recurrent miscarriage when there is early pregnancy bleeding in the current pregnancy (Progesterone in Spontaneous Miscarriage, PRISM trial, 2019).

Self-administered progesterone pessaries can be offered in this case.

    • 1st line : Cyclogest 400mg, administered vaginally twice a day.
    • 2nd line Utrogestan 400mg, administered vaginally twice a day.

Progesterone is not thought to improve the pregnancy outcome in those with RM without early pregnancy bleeding (Progesterone in Recurrent Miscarriage, PROMISE, 2015). Women with unexplained RM may choose to take Cyclogest from earlier in the pregnancy in the absence of bleeding but should be informed that this is not evidence based.

  • Hysteroscopic resection of a uterine septum or removal of submucosal fibroid or polyps:

This may be discussed and offered in certain circumstances although there is limited evidence that it reduces the rate of RM

  • Recurrent second trimester losses:

Recurrent pregnancy loss in the second trimester is associated with cervical weakness and therefore and individualised plan for obstetric led care with serial cervical length scans +/-cervical cerclage is recommended.

  • Treatment with the following is not routinely recommended:
    • Hcg
    • Metformin
    • Heparin or aspirin for unexplained RPL
    • Intralipid
    • IV immunoglobulin
    • Endometrial scratch
    • Pre-implantation genetic screening in conjunction with IVF/ICSI due to the lack of evidence that this improves reproductive outcomes.

Patient Information Leaflets and Support

Editorial Information

Last reviewed: 14/05/2024

Next review date: 31/05/2028

Author(s): Dr Lynne Thomson, Consultant O&G, QEUH.

Version: 2

Co-Author(s): Dr Judith Roberts, Consultant O&G, QEUH, Dr Joy Simpson, Consultant O&G PRM.

Approved By: Gynaecology Governance Group

Document Id: 708

References

Regan L, Rai R, Saravelos S, Li T-C, on behalf of the Royal College of Obstetricians and Gynaecologists. Recurrent Miscarriage: Green-top Guideline No. 17. BJOG. 2023; 130(12): e9–e39. 

Recurrent Pregnancy Loss, European Society of Human Reproduction and Embryology (ESHRE), Update 2022  ESHRE RPL Guideline _ Update 2022_ Final Version January 2023_v2.pdf

NICE Guideline (NG126) April 2019, update August 2023 Recommendations | Ectopic pregnancy and miscarriage: diagnosis and initial management | Guidance | NICE

Coomarasamy A, et al A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy, May 9, 2019 N Engl J Med 2019; 380:1815-1824 

Dhillon-Smith RK, Boelaert K, Jeve YB, Maheshwari A, Coomarasamy A; on behalf of Royal College of Obstetricians and Gynaecologists. Subclinical hypothyroidism and antithyroid autoantibodies in women with subfertility or recurrent pregnancy loss. Scientific impact paper no. 78. BJOG. 2022; 129: e75–e88. 

Nybo Andersen AM, Wohlfahrt J, Christens P, Olsen J, Melbye M. Maternal age and fetal loss: population based register linkage study. BMJ. 2000 Jun 24;320(7251):1708-12.