Approach
Vaginal bleeding in pregnancy should be seen as a clinical continuum as many women who experience spontaneous vaginal bleeding in the first half of pregnancy continue their pregnancies without any other complications. The main aims of treatment are to help the patient (or couple) understand the problem, advise on management, and offer follow-up independent of the outcome. Symptomatic management is necessary. [Figure caption and citation for the preceding image starts]: The natural course of miscarriageFrom: Ankum WM, Wieringa-de Ward M, Bindels PJE. BMJ 2001 Jun 2;322(7298):1343-6. [Citation ends].
A woman who has experienced multiple miscarriages discusses with a doctor how best to counsel patients on experiencing bleeding and pain during pregnancy, including management of expectations.
Initial treatment
Management is best undertaken in a unit with experience of managing early pregnancy complications.[10][91] In women with heavy vaginal bleeding, immediate care includes the establishment of venous access and monitoring of the vital signs and fluid balance. Blood should be sent for grouping and crossmatch, including identification of mothers with a negative rhesus blood group. Consider a request for blood culture if the patient is febrile. Those with severe vaginal bleeding and /or hypotension may need a urinary catheter to monitor urinary output. They may also be anemic, requiring correction and continued monitoring. Identification and appropriate treatment must be carried out if there are any comorbid medical disorders. Analgesia is imperative in the presence of pain and discomfort, although the use of nonsteroidal anti-inflammatory drugs is best avoided.
Threatened miscarriage
Patients with threatened miscarriage are treated conservatively with symptomatic treatment of pain, with the hopeful expectation that there will be a non-progression to inevitable miscarriage. Pregnancies that continue require closer follow-up and targeted fetal surveillance.[92] Patients should be reassured that many pregnancies following a threatened miscarriage have a satisfactory outcome. They should be advised that if bleeding gets worse, or persists beyond 14 days, they need to return for further evaluation.[3] If the bleeding stops, patients should start or continue routine prenatal care.[68]
Vaginal progesterone may be recommended in some countries. In the UK, the National Institute for Health and Care Excellence (NICE) recommends offering vaginal micronized progesterone to women with an intrauterine pregnancy confirmed by a scan, if they have vaginal bleeding and have previously had a miscarriage.[68] If a fetal heartbeat is confirmed, progesterone should be continued until 16 completed weeks of pregnancy.[68]
The NICE recommendation for progesterone is based on evidence from a Cochrane network meta-analysis, which included the PRogesterone In Spontaneous Miscarriage (PRISM) trial. Findings from PRISM showed that although progesterone did not reduce the rate of miscarriage in women with no previous miscarriage, there was a small reduction in miscarriage among those with 1-2 previous miscarriages, and a much greater reduction among those with ≥3 previous miscarriages.[93] The Cochrane network meta-analysis concluded that vaginal micronized progesterone may increase the live birth rate for women with a history of 1 or more previous miscarriages and early pregnancy bleeding, with likely no difference in adverse events.[94]
Clinical opinion on the utility of progesterone and other progestogens for threatened miscarriage remains mixed, and is not currently recommended in US practice.[95] Further research is needed to better understand the potential of progestogens for preventing miscarriage in women with early bleeding but no previous miscarriage, and in women with previous miscarriage but no early bleeding.[68][94]
Inevitable/incomplete/missed miscarriage
Early pregnancy tissue visualized in the vagina or cervical os:
The presence of early pregnancy tissue within the dilated cervical canal may trigger a vasovagal reflex. This may be accompanied by significant vaginal bleeding, pelvic discomfort or pain, faintness, or a feeling of fullness within the vagina.
Prompt removal of the early pregnancy tissue digitally or with a sterile ovum or sponge-holding forceps should be carried out if seen in the upper vagina or cervical canal. There will be little bleeding once the uterine cavity is empty and the patient recovers.
Those with severe vaginal bleeding or those who continue to bleed after manual evacuation should receive misoprostol, a prostaglandin analog, even if the early pregnancy tissue is removed from the upper vagina or cervical canal. This will aid complete emptying of the uterine cavity.[96]
Early pregnancy tissue not visualized in the vagina or cervical os:
Ultrasound is preferred for confirming early pregnancy loss.[95]
The intensity of bleeding and the thickness of the shadow within the uterine cavity on ultrasound influence the choice of management: conservative, medical (with a prostaglandin analog, misoprostol), or surgical evacuation for the remaining early pregnancy tissue.[97][98] The American College of Obstetricians and Gynecologists (ACOG) recommends that surgical intervention is not required in asymptomatic women who have a thickened endometrial stripe after undergoing treatment for pregnancy loss.[95]
When the antero-posterior diameter of the heterogenous shadow within the endometrial cavity is less than 15 mm, it is unlikely that surgical evacuation will yield much.[99][100] Even this cut-off value has poor sensitivity in excluding retained early pregnancy tissue.[101] However, until larger studies are undertaken, 15 mm is presently widely used as a cut-off point. The treatment options also depend on the experience of the doctor, efficacy of the option, adverse effects, and complications.[102] Patients/couples may have their own choices, and clinicians should support a patient's decision after clearly outlining any risks involved.[103] No differences in conception rates within 5 years of the index miscarriage were noted in a study of 1128 women after expectant, medical, or surgical management of spontaneous first-trimester miscarriage, although older women and those with remote miscarriages have lower rates.[104] Patients with a missed miscarriage should be counseled that medical management may increase the intensity and duration of lower abdominal cramping and genital blood loss.[102][105] Patients with an endometrial thickness between 15-50 mm on ultrasound should be offered medical management or be conservatively managed. Women with an endometrial thickness >50 mm on ultrasound may be offered surgical evacuation. All three management options after a missed miscarriage may also be left for the patient or couple to decide.
Conservative management:
A significant number of women prefer conservative (or expectant) management, in which natural processes lead to the early pregnancy tissue being expelled spontaneously.
It may be continued as long as the patient is willing and provided there are no signs of infection such as vaginal discharge, feeling ill, excessive bleeding, pyrexia, or lower abdominal pain.
In the US, the ACOG practice bulletin states that with adequate time (up to 8 weeks), expectant management is successful in around 80% of women, but should be limited to the first trimester because of the lack of safety studies. An ultrasound can be used to confirm the outcome, with absence of gestational sac and an endometrial thickness of <30 mm. There is no specific guidance on when or how frequently to evaluate.[95]
NICE guidelines recommend expectant management (for 7-14 days) as the preferred first-line management strategy for women with a confirmed diagnosis of miscarriage, with review of their condition after a minimum of 14 days if they opt for continued expectant management. Exceptions include:[68]
women at increased risk of hemorrhage
women at increased risk from the effects of hemorrhage;
a history of previous adverse and/or traumatic experiences with pregnancy; or
evidence of infection.
Conservative management is not a safe option if there is a suspicion or a diagnosis of genital tract infection.
Follow-up scans may be arranged at 2-weekly intervals, until a diagnosis of complete miscarriage is made. One study recommends a "2-week wait-and-see" approach that may be offered to women with missed miscarriage, anembryonic pregnancy, or incomplete miscarriage, when patients initially opt for conservative management.[106] Weekly transvaginal ultrasound scans were performed to monitor patients. At the end of 2 weeks, 71% of incomplete miscarriages, 53% of anembryonic pregnancies, and 35% of missed miscarriages had resolved.
Surgical management of miscarriage:
This is quick and a once-only procedure in the presence of moderate to severe vaginal bleeding. However, it includes risks associated with general anesthesia, heavy bleeding, infection, intrauterine adhesions, cervical trauma, or uterine perforation. RCOG: surgical management of miscarriage and removal of persistent placental or fetal remains Opens in new window Decision regarding surgical management also depends on the clinical and cardiovascular status of the patient, the gestational age, available clinical equipment, and clinical skills.
Suction evacuation of the uterus is preferable to the use of metal curettage.[107] Vaginal bleeding stops soon after, and the patient resumes her pre-miscarriage menstrual status more quickly.
The manual vacuum aspiration technique is a versatile technique of uterine evacuation in missed and incomplete miscarriage.[108] The attraction of this technique is that it may be performed without the need of operating room space and time, or a need for a general anesthetic. Patients may also find it acceptable because it makes uterine evacuation an essentially "office procedure."[95]
A review suggested that suction evacuation is preferably indicated if bleeding remains heavy, there is demonstrable retained early pregnancy tissue on ultrasound, or if there are signs of infected early pregnancy tissue or endometritis.[109]
An oxytocic may be used to facilitate or to effect uterine evacuation in patients undergoing surgical evacuation and to prevent postprocedure bleeding.
Medical evacuation:
Drugs used to facilitate or to effect uterine evacuation may have a role where vaginal bleeding is reasonably mild.[110][111][112] The main drug for medical uterine evacuation is misoprostol.[95] One 2018 randomized controlled trial found that pretreatment with mifepristone followed by a single dose of misoprostol resulted in a higher likelihood of successful management of first-trimester pregnancy loss compared with misoprostol alone (complete expulsion in 83.8% vs. 67.1%; relative risk, 1.25; 95% CI, 1.09 to 1.43). However, the study highlighted that administrative barriers mean that this treatment is not widely available for this indication.[113]
The patient needs to be informed that the surgical option may still be necessary if bleeding gets heavier or is persistent beyond a reasonable time.
Patients should be provided with a urine pregnancy test to carry out at home 3 weeks after medical management.[68] Patients should be advised to return to the healthcare professional responsible for their medical management should they experience worsening symptoms.[68]
Brisk bleeding may follow complete evacuation of the uterus. The first maneuver is to bimanually compress the uterus. It is sometimes necessary to administer oxytocin or prostaglandin analogs to reduce the chances of postmiscarriage bleeding.
A study comparing expectant, medical, and surgical management of incomplete miscarriage or early fetal demise at gestational ages below 13 weeks found that the number of unplanned hospital admissions was significantly higher in the expectant group (49%) as compared with the medical (18%) or surgical (8%) groups. A little over one third of the women (36%) allocated to medical treatment, and 44% of those allocated to expectant management, needed an unplanned suction curettage.[111]
The use of routine antibiotic prophylaxis in women with incomplete miscarriage and no signs of infection is controversial.[114] Women with incomplete miscarriage who have one or more features: a foul-smelling vaginal discharge, fever, chills, lower abdominal pain, or feeling ill, may benefit from a preoperative course of antibiotics to be administered at least 1 hour before uterine evacuation.[115] Oral antibiotics may be prescribed for at least 3 days after surgery. In one study, administration of intravenous antibiotics preoperatively showed that oral antibiotics may not be necessary after 48 hours of clinical improvement.[116]
The Human Tissue Authority specifies that women should be made aware of disposal options available. It is important to discuss disposal choices with women when consenting for surgical management of miscarriage and to obtain informed consent regarding what should happen to pregnancy remains.[3]
Complete miscarriage
The treatment for these patients is symptomatic. They should receive analgesics as required and counseling for the loss of pregnancy.
Recurrent miscarriage
Although 1 in 5 women with a history of recurrent miscarriage may have further pregnancy loss, the other proportion do well, without any intervention. For example, after 3 consecutive unexplained miscarriages up to 75% of women are likely to have a successful pregnancy.[117] Also, currently unexplained causes of recurrent miscarriage may be elucidated in the future, as a better understanding of the types of recurrent miscarriage could lead to more targeted referrals, investigations, and treatments.[118]
The European Society for Human Reproduction and Gynaecology has provided recommendations for the treatment of recurrent miscarriage.[77]
No intervention is advised in women with unexplained miscarriage:
Multivitamins and folic acid supplementation: these have no confirmed benefit and are not recommended as treatment. However, if patients ask about using supplements you should advise which ones are safe in pregnancy as some supplements are associated with possible harms.
It should be remembered that clinical evaluation of potential treatments for recurrent miscarriage are best undertaken in the context of controlled clinical trials. If a physician offers empirical treatment, it should be made clear to the patient that this is a departure from optimum clinical practice.[3]
Patients with an identifiable cause:
Cervical cerclage may benefit patients with second-trimester recurrent miscarriages possibly explained by cervical incompetence, insufficiency, or weakness. One or more of consecutive pregnancies might have been delivered very prematurely.
Neither anticoagulants nor aspirin have been shown to help prevent early pregnancy loss in women with unexplained pregnancy loss or with thrombophilias (excluding those with antiphospholipid syndrome).[95][77][119][120][121][Evidence C]
Patients with antiphospholipid syndrome or multiple inherited thrombophilias have been treated with low-dose aspirin that is started before conception. These patients may also require heparin therapy following a positive pregnancy test, until delivery. Addition of unfractionated heparin is more effective at reducing pregnancy loss as compared with the addition of low-molecular-weight heparin.[122]
There is conflicting evidence regarding treatment with metformin of some women with polycystic ovarian disease in reducing miscarriage rates.[77] It may act by inhibiting plasminogen activator, lowering levels of androgens, and improving the quality of the oocytes.
With regards to immunotherapy in the treatment of unexplained miscarriage, paternal cell immunization, third-party donor leukocytes, trophoblast membranes, and intravenous immunoglobulin provide no significant beneficial effect over placebo in improving the live birth rate.[123] [
]
Couples with a risk or history of recurrent miscarriage present an emotional and professional challenge to the physician. Many will do everything possible to sustain a pregnancy. Referral to a regional research unit is often appreciated, even if no successful pregnancy is eventually achieved.
Rho (D) immune globulin
In the US, ACOG recommends that women who are rhesus negative and unsensitized should receive Rho (D) immune globulin within 72 hours of a potentially sensitizing event in the first or second trimester. However, whether to administer Rho (D) immune globulin to a patient with threatened pregnancy loss and a live embryo or fetus at or before 12 weeks of gestation is controversial, and no evidence-based recommendation can be made. Because of the higher risk of alloimmunization, rhesus-negative women who receive surgical management of their miscarriage should receive Rh D prophylaxis.[95][124]
Counseling
All patients should be provided with information on counseling services. Physicians and healthcare facilities should have mechanisms in place to support mothers (or couples) who miscarry. A patient information pamphlet is useful. Some women may need psychological or psychiatric support.
Couples who have just lost an early pregnancy may also worry about what to tell friends and relatives. Loss of an early pregnancy can affect couples as significantly as a neonatal death, and is especially devastating for people who have undergone treatment for subfertility. The patient may experience guilt in addition to grief. Social, family, or spiritual support may be invaluable in this circumstance. The extremely low chance of repeat miscarriage should be mentioned if any worry is expressed about the future. When a missed miscarriage is diagnosed, the woman (or the couple) may want a second opinion or another scan just to be sure. The physician must endeavor to accept this with understanding.
The use of video, workbook, and nurse-caring counseling sessions have been shown to have a place in couple-focused intervention in the first months after miscarriage.[125] The pattern and context of psychological consequences of early pregnancy loss vary from couple to couple, and within social settings. Measures that would work for a patient and her partner, to facilitate grief and resolution, need to be tailored to pre-event expectations, support systems, and coping mechanisms. The patient's family physician, gynecologist, or nurse may offer valuable insight and support. In the UK, the Sands (Stillbirth and Neonatal Death Charity) guidelines are widely recognized as an essential benchmark for good practice when caring for parents who have a childbearing loss. Stillbirth and Neonatal Death Charity Opens in new window
A less frequently considered clinical circumstance is pregnancy loss in a nonheterosexual woman. A most instructive article on this subject advises that healthcare professionals (1) identify the sex of partners, (2) acknowledge and actively include same-sex partners, and (3) demonstrate awareness and sensitivity to the likelihood that the pregnancy of a nonheterosexual woman has involved lengthy planning and resources.[126]
Depending on hospital or healthcare facility policy, the removed early pregnancy tissue may be sent for histopathology after obtaining parental consent and offering counseling.
A woman who has experienced multiple miscarriages and a doctor explore the benefits of professional and personal support networks following miscarriage, as well as practical tips on how to manage anxiety induced by miscarriage.
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