Rationale and impact
These sections briefly explain why the committee made the recommendations and how they might affect practice.
There was good evidence that, when seen on ultrasound, the presence of an adnexal mass with features of an early pregnancy (a gestational sac containing a yolk sac or fetal pole, with or without a heartbeat) was a reliable indicator for ectopic pregnancy.
Other features such as a complex inhomogeneous adnexal mass, adnexal mass with an empty gestational sac, empty uterus, a collection of fluid in the uterine cavity or free peritoneal fluid might indicate a suspicion of an ectopic pregnancy, but the evidence showed they are not reliable enough features on their own to diagnose an ectopic pregnancy. The committee used their knowledge and experience to recommend that other scan features, clinical presentation and serum human chorionic gonadotrophin (hCG) levels should therefore be used as well to confirm or rule out the diagnosis of ectopic pregnancy.
The recommendations will not change the amount of ultrasound scanning that is carried out but will standardise practice across the NHS. By defining the features that should be used to indicate the presence of an ectopic pregnancy, or a suspicion of an ectopic pregnancy (which can then be investigated further), the diagnosis of ectopic pregnancy should be improved and so risks to women will be reduced.
There was good evidence that 400 mg twice daily of micronised vaginal progesterone increases the number of live births in women with early pregnancy bleeding and a previous miscarriage. There was no evidence of benefit for any other preparations or doses of progesterone, so the committee made a recommendation for research.
There was evidence of no benefit in women with early pregnancy bleeding but no previous miscarriage, nor in women with previous miscarriage but no early pregnancy bleeding in the current pregnancy. The committee made a recommendation for research to further assess the use of progesterone in women with recurrent miscarriage. There was no evidence of harm to the mother or baby from the use of progesterone, although the evidence is insufficient to rule out the possibility of rare events.
To reduce the risk of women with a pregnancy of unknown location or an ectopic pregnancy being given progesterone, the committee agreed that, as in the clinical studies, progesterone should only be given to women with intrauterine pregnancy confirmed with a scan. To avoid delay in starting treatment the committee agreed that progesterone could be started before a fetal heartbeat is detected. The evidence on which the recommendations were based had continued the progesterone treatment until 16 weeks of pregnancy so the committee used this duration of treatment in their recommendations.
The committee discussed that as a scan was needed to confirm the intrauterine pregnancy it would be appropriate for the initial prescription for progesterone to be provided by the Early Pregnancy Unit, with prescribing continued to 16 weeks (if a fetal heartbeat was detected) by the woman's GP. However, the committee were aware that shared care prescribing arrangements are usually agreed locally and so did not include this detail in their recommendations.
The committee confirmed that the recommendations for the use of progesterone are only for women with early pregnancy bleeding and a history of miscarriage. The recommendations are not applicable in other circumstances, such as after the use of mifepristone.
The recommendations will increase the use of progestogens to prevent miscarriage but this is cost effective. The recommendations will standardise the preparation of progesterone used to treat threatened miscarriage.
There was evidence that the combination of mifepristone and misoprostol reduced the failure of the gestational sac to spontaneously pass by 7 days and reduced the need for surgical intervention to complete the miscarriage up to and after 7 days, compared to misoprostol alone, so the committee recommended a combination treatment.
Time to bleeding was not an outcome reported in the evidence, but the committee noted that the evidence described that bleeding usually started 2 to 3 days after misoprostol treatment, and that study participants were asked to report if bleeding had not started within 48 hours. The committee agreed that 24 hours was too short and so recommended 48 hours as a more realistic timeframe. Based on their knowledge and experience, the committee noted that there may be some people who cannot easily contact early pregnancy services, so it recommended these individuals should be contacted proactively to check that bleeding has begun.
The committee revised the recommendations on incomplete and missed miscarriage to clarify the differences between the treatment of the 2 conditions. The committee reviewed new evidence relating to the use of mifepristone for missed miscarriage and added this to the advice, but agreed that there was no new evidence to support the use of mifepristone for incomplete miscarriage.
The committee agreed, based on their knowledge and experience, that women and people having a miscarriage should also be given advice on when and how to seek help during the miscarriage process, so it added this to the existing advice.
The committee agreed that a positive pregnancy test may indicate the presence of a retained pregnancy, so it added this to the recommendation on when to return for review. Based on expert advice, the committee added additional advice to cover the situation where the pregnancy test is negative but the woman or person is still bleeding or has developed other symptoms.
The committee noted that the recommendation on expectant management of miscarriage stated people should obtain a pregnancy test themselves, whereas the guidance following medical management of miscarriage advised that people should be supplied with a pregnancy test by their care team. To ensure parity of treatment between all groups having a miscarriage, the committee updated this recommendation based on expert opinion and consensus.
The recommendation for combination treatment will be a change in practice and women or people being treated for missed miscarriage will now need to receive 2 medications instead of 1, administered 48 hours apart. The use of mifepristone for the treatment of missed miscarriage may also increase. However, as mifepristone is already used in clinical practice for missed miscarriage in many early pregnancy settings this will standardise practice for such settings across the NHS. The use of combination treatment will also reduce the need for surgical intervention so will reduce costs for the NHS. This has been shown to be a cost-effective treatment.
The change from 24 hours to 48 hours in the recommendation on start of bleeding may reduce the number of people contacting early pregnancy services because bleeding has not started. However, the recommendation to proactively follow up with people who do not contact the service may increase resource use, as staff time will be needed to contact these individuals.
This addition of advice on how and when to seek help may increase the number of people seeking help during the miscarriage process, and this may increase resource use for the NHS.
The revised recommendation on positive urine pregnancy tests will not change the number of people who need review after 3 weeks, so there will be no resource impact from this change.
The change to the expectant management advice to give parity of care will increase the number of urine pregnancy tests supplied by the NHS, which will have a resource impact, but this will reduce health inequalities and ensure that all women and people have access to the pregnancy test to complete their management of miscarriage regardless of ability (financial or otherwise) to obtain a pregnancy test themselves.
The evidence showed no significant differences in the number of ectopic pregnancies ending naturally, the need for additional treatment, the incidence of tubal rupture or the effect on health-related quality of life between expectant management and medical management, so the committee recommended that expectant management could be offered to clinically stable women with small ectopic pregnancies and low hCG levels, and should be considered for clinically stable women with small ectopic pregnancies and slightly higher hCG levels, as an alternative to medical management.
There was no evidence for the time taken for ectopic pregnancies to end naturally or the effects on future fertility but the committee agreed, based on their expertise and experience, that these outcomes were likely to be the same with expectant management compared with medical management.
These recommendations will standardise the management of ectopic pregnancy and make expectant management available for women when it is clinically appropriate. More women might have expectant management of ectopic pregnancy as a result. This could result in cost savings through a reduction in drug use and treatment of associated side effects. Local protocols will be needed for assessment, monitoring and follow-up of women choosing expectant management.