Early Pregnancy Loss in the 1st Trimester

Abstract

Purpose This guideline aims to improve and standardize the diagnostic and therapeutic approaches for different types of miscarriages, pregnancies of unclear localization, and ectopic pregnancies in the 1st trimester.

Methods In accordance with the requirements for an S2k-guideline, this guideline was compiled following a search of the literature, and the various recommendations and statements were formally agreed upon by an interdisciplinary group of representative experts from Germany (DGGG, etc.), Austria (OEGGG) and Switzerland (SGGG) who met up several times under the aegis of the German Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG).

Recommendations The guideline provides 129 recommendations on clinical, laboratory-based, ultrasonographical, pathomorphological and genetic diagnostics and describes and assesses different therapeutic options in terms of their success and complication rates and the continued fertility of the patient as well as aspects of the grieving process and coming to terms with the loss after an early loss of pregnancy.

Keywords

guideline - miscarriage - ectopic pregnancy - pregnancy of unknown localization

I  Guideline Information

Guidelines program of the DGGG, OEGGG and SGGG

More information on the program is available at the end of the guideline.

Citation format

Early Pregnancy Loss in the 1st Trimester. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/076; August 2024). Geburtsh Frauenheilk 2025; 85: 282–310

Guideline documents

The complete long version in German, a slide version of this guideline, and a list of the conflicts of interest of all authors is available on the homepage of the AWMF: http://www.awmf.org/leitlinien/detail/ll/015-074.html

Guideline authors

See [Tables 1] and [2].

Table 1 Lead and/or coordinating guideline authors.

Author	AWMF professional society
Prof. Dr. med. Matthias David	German Society for Gynecology and Obstetrics [Deutsche Gesellschaft für Gynäkologie und Geburtshilfe e. V.] (DGGG)
Prof. Dr. med. Sven Becker	German Society for Gynecology and Obstetrics (DGGG)

Table 2 Involved professional societies, organizations, etc.

DGGG working group/AWMF/non-AWMF professional society/organization/association
Professional Association of Gynecologists [Berufsverband der Frauenärzte e. V.] (BVF)
German Society for Gynecology and Obstetrics (DGGG)
Gynecological Endoscopy Working Group [Arbeitsgemeinschaft für Gynäkologische Endoskopie] (AGE)
Gynecology and Obstetrics Working Group [Arbeitsgemeinschaft für Gynäkologie und Geburtshilfe] (AGG)
Working Group on Ultrasound Diagnostics in Gynecology and Obstetrics [Arbeitsgemeinschaft für Ultraschalldiagnostik in Gynäkologie und Geburtshilfe] (ARGUS)
German Society for Gynecological Endocrinology and Reproductive Medicine [Deutsche Gesellschaft für Gynäkologische Endokrinologie und Fortpflanzungsmedizin e. V.] (DGGEF)
German Society for Psychosomatic Gynecology and Obstetrics [Deutsche Gesellschaft für Psychosomatische Frauenheilkunde und Geburtshilfe e. V.] (DGPFG)
German Society for Reproductive Medicine [Deutsche Gesellschaft für Reproduktionsmedizin e. V.] (DGRM)
German Society for Ultrasound in Medicine [Deutsche Gesellschaft für Ultraschall in der Medizin e. V.] (DEGUM)
German Society of Pathology [Deutsche Gesellschaft für Pathologie e. V.] (DGP)
German Society for Clinical Chemistry and Laboratory Medicine [Deutsche Gesellschaft für Klinische Chemie und Laboratoriumsmedizin e. V.] (DGKL)
German Society of Human Genetics [Gesellschaft für Humangenetik e. V.] (GfH)
Austrian Society for Gynecology and Obstetrics [Österreichische Gesellschaft für Gynäkologie und Geburtshilfe] (OEGGG)
Swiss Society for Gynecology and Obstetrics [Schweizerische Gesellschaft für Gynäkologie und Geburtshilfe] (SGGG)

The following professional societies/working groups/organizations/associations nominated representatives to assist in the compilation of the guideline ([Table 2]).

Involvement of target patient group

Organization: Online forum fehlgeburt.info

The structured consensus process was moderated by Dipl.-Biol. Simone Witzel (AWMF-certified guidelines consultant/moderator).

II  Guideline Application

Purpose and objectives

The guideline aims to improve and standardize diagnostic and therapeutic approaches for different types of miscarriages, pregnancies of unclear localization, and ectopic pregnancies in the 1st trimester of pregnancy.

The following content-related objectives of the guideline were defined:

1. Provide information on laboratory-based, ultrasonography and genetic diagnostics

2. Present and assess different therapeutic options in terms of success and complication rates and the continued fertility of the patient

3. Include aspects of the grieving process and coming to terms with the loss after an early loss of pregnancy

Targeted areas of care

• Inpatient care sector

• Outpatient care sector

• Short-term inpatient care sector

• Primary medical care

• Specialist care

Target user groups/target audience

This guideline is aimed at:

• gynecologists and obstetricians

• professional medical societies

• working groups

• organizations involved in the compilation of the guideline

• patients

Adoption and period of validity

The validity of this guideline was confirmed by the executive boards/representatives of the participating medical professional societies, working groups, organizations, and associations as well as the boards of the DGGG and the DGGG Guidelines Commission and of the SGGG and OEGGG in July 2024 and was thereby approved in its entirety. This guideline is valid from 1 September 2024 through to 31 August 2029. Because of the contents of this guideline, this period of validity is only an estimate.

III  Method

Basic principles

The method used to prepare this guideline was determined by the class to which this guideline was assigned. The AWMF Guidance Manual (version 1.0) has set out the respective rules and requirements for different classes of guidelines. Guidelines are differentiated into lowest (S1), intermediate (S2), and highest (S3) class. The lowest class is defined as consisting of a set of recommendations for action compiled by a non-representative group of experts. In 2004, the S2 class was divided into two subclasses: a systematic evidence-based subclass (S2e) and a structural consensus-based subclass (S2k). The highest S3 class combines both approaches.

This guideline was classifed as: S2k

Grading of recommendations

The grading of evidence based on the systematic search, selection, evaluation, and synthesis of an evidence base which is then used to grade the recommendations of the guideline is not envisaged for S2k guidelines. The individual statements and recommendations are only differentiated by syntax, not by symbols ([Table 3]).

Table 3 Grading of recommendations (based on Lomotan et al., Qual Saf Health Care 2010).

Description of binding character	Expression
Strong recommendation with highly binding character	must/must not
Regular recommendation with moderately binding character	should/should not
Open recommendation with limited binding character	may/may not

Statements

Expositions or explanations of specific facts, circumstances, or problems without any direct recommendations for action included in this guideline are referred to as “statements.” It is not possible to provide any information about the level of evidence for these statements.

Achieving consensus and level of consensus

At structured NIH-type consensus conferences (S2k/S3 level), authorized participants attending the session vote on draft statements and recommendations. The process is as follows. A recommendation is presented, its contents are discussed, proposed changes are put forward, and all proposed changes are voted on. If a consensus (> 75% of votes) is not achieved, there is another round of discussions, followed by a repeat vote. Finally, the level of consensus is determined, based on the number of participants ([Table 4]).

Table 4 Level of consensus based on extent of agreement.

Symbol	Level of consensus	Extent of agreement in percent
+++	Strong consensus	> 95% of participants agree
++	Consensus	> 75 to 95% of participants agree
+	Majority agreement	> 50 to 75% of participants agree
–	No consensus	< 51% of participants agree

Expert consensus

As the term already indicates, this refers to consensus decisions relating specifically to recommendations/statements issued without a prior systematic search of the literature (S2k) or where evidence is lacking (S2e/S3). The term “expert consensus” (EC) used here is synonymous with terms used in other guidelines such as “good clinical practice” (GCP) or “clinical consensus point” (CCP). The strength of the recommendation is graded as previously described in the chapter Grading of recommendations but without the use of symbols; it is only expressed semantically (“must”/“must not” or “should”/“should not” or “may”/“may not”).

IV  Guideline

Preamble

When caring for and treating patients who have suffered an early loss of pregnancy (miscarriage, ectopic pregnancy), medical and nursing staff are expected to show a sensitive and empathetic approach to the individual patientʼs psychological situation in the same way they would be expected to deal with other clinical disorders. Patients in the same clinical situation may have different ideas about the right approach for themselves. However, an empathetic response to the patientʼs wishes assumes that the situation is not life-threatening as this would need to be expressly pointed out to the affected woman. Treatment recommendations must always be guided by medical requirements. But it is important to bear in mind that the patient will have to cope with the experience of loss for a long time to come.

Affected women have the right to be supported by a midwife before, during and after a miscarriage.

Definition of disorders of early pregnancy

An early loss of pregnancy is defined as a non-viable pregnancy with an empty gestational sac or a gestational sac with an embryo or fetus without cardiac activity in the first 12 weeks of pregnancy post conception, localized inside or outside the uterus (modified from [1]).

The aim of this guideline is to improve the care provided to affected women who suffer an early loss of pregnancy.

The guideline reviews practice-based diagnostic approaches and current treatment options for early loss of pregnancy.

Early loss of an intrauterine or ectopic pregnancy is quite common and probably occurs in at least 10 to 15% of all clinically detected pregnancies, which amounts to about 23 million miscarriages annually [1], [2], [3]. Around 80% of all pregnancy losses occur in the first trimester of pregnancy [1]. This is a significant burden on resources in the healthcare sector. In Great Britain, for example, it is associated with more than 50 000 hospital admissions every year [2].

Most affected women are not aware of how common early loss of pregnancy is. While an early loss of pregnancy represents a routine situation for doctors, the unfavorable pregnancy outcome is usually unexpected for the patient and can be psychologically very stressful. After treatment for miscarriage or ectopic pregnancy, the patient may experience symptoms of depression, anxiety, and post-traumatic stress disorder [4]. It is therefore important that the psychological impact of an early loss of pregnancy on the affected woman receives sufficient attention during her medical care. From a medical perspective, the focus must be initially on confirming the diagnosis and averting danger to the patient and managing the (“somatic”) emergency situation.

If the clinical situation permits, gynecologists must explain and offer the whole range of options available to treat miscarriage or suspected ectopic pregnancy to patients which, in addition to expectant management, also includes drug treatment and surgery.

If women exhibit no emergency symptoms or medical complications which require urgent surgical intervention, planned treatment may accommodate the patientʼs preferences after she has been informed in detail about the risks and advantages of each option [1]. The aim is to develop an individual treatment path based on shared decision-making. Confirmation of the diagnosis is essential before starting treatment as it is important to differentiate an intact pregnancy from a miscarriage, an ectopic pregnancy, trophoblastic disease or molar pregnancy, or a pregnancy of unclear localization.

All recommendations and statements of the guideline are presented below.

Pregnancy of unclear localization

Consensus-based recommendation 2.E1
Expert consensus	Level of consensus +++
The diagnostic workup and definition of a pregnancy of unclear localization must include the patientʼs gynecological history (especially her prior cycle history), a clinical examination, transvaginal ultrasound, and quantitative determination of β-hCG.

Consensus-based recommendation 2.E2
Expert consensus	Level of consensus +++
Combining a single β-hCG value with sonographic imaging showing an empty uterine cavity must not immediately lead to the diagnostic assumption of an ectopic pregnancy.

Consensus-based recommendation 2.E3
Expert consensus	Level of consensus ++
If a pregnancy of unclear localization is suspected, the changes in β-hCG levels should be determined after 48 hours and transvaginal ultrasound examinations should be carried out.

Consensus-based recommendation 2.E4
Expert consensus	Level of consensus ++
Invasive diagnostic or therapeutic procedures should only be used if the patient has otherwise unexplained pain symptoms or persistent pregnancy of unclear localization.

Consensus-based statement 2.S1
Expert consensus	Level of consensus +++
Use of the M6/M6NP (and M4) models to triage pregnant women with a pregnancy of unclear localization can be useful to support clinical decision-making.

Miscarriage/spontaneous abortion

Consensus-based recommendation 3.E5
Expert consensus	Level of consensus +++
If a disorder of early pregnancy is suspected, the changes in β-hCG concentrations over time should be monitored. If there is bleeding, blood group determination including Rhesus factor determination should be carried out.

Consensus-based statement 3.S2
Expert consensus	Level of consensus +++
A speculum examination may be carried out to confirm whether genital bleeding is uterine bleeding. Palpation during gynecological examination is done mainly to diagnose the cause of acute pain with suspected ectopic pregnancy or, if the cervix is dilated, to diagnose imminent miscarriage. Tenderness of one of the adnexa on palpation may serve to quickly identify an acute situation in a case with ectopic pregnancy.

Consensus-based recommendation 3.E6
Expert consensus	Level of consensus +++
Transvaginal sonography should be the preferred diagnostic approach for symptomatic women to localize the pregnancy and assess the current situation in the event of a miscarriage.

Consensus-based recommendation 3.E7
Expert consensus	Level of consensus +++
Unless there is a defined emergency situation, the patient should be informed about the alternatives “expectant approach” and “interventional approach”.

Treatment options

1. Expectant approach

Consensus-based recommendation 3.E8
Expert consensus	Level of consensus +++
The patient must be informed about the risks associated with each type of approach (expectant/drug-based/surgical).

Consensus-based recommendation 3.E9
Expert consensus	Level of consensus +++
If an expectant approach is chosen, the information provided to the patient about the risk of requiring surgical intervention or a drug-based approach should be recorded.

Consensus-based recommendation 3.E10
Expert consensus	Level of consensus +++
Patients with spontaneous abortion should also be offered an expectant approach once any contraindications have been excluded.

Consensus-based recommendation 3.E11
Expert consensus	Level of consensus +++
Women suffering a miscarriage who opt for an expectant approach must be informed about what they can expect during the entire process of the miscarriage including pain, and they must receive treatment suggestions for pain relief.

Consensus-based recommendation 3.E12
Expert consensus	Level of consensus +++
Non-steroidal anti-inflammatory drugs such as ibuprofen or metamizole should be recommended as pain relief to women who opt for an expectant approach when suffering a miscarriage in the first trimester of pregnancy.

Consensus-based recommendation 3.E13
Expert consensus	Level of consensus +++
If the patient has opted for an expectant approach, she must be informed that it can take longer until the miscarriage is complete and that it may be accompanied by increased blood loss and severe pain.

Consensus-based recommendation 3.E14
Expert consensus	Level of consensus +++
The patient must be informed about the necessity of surgical or drug-based follow-up treatment in the event that the miscarriage is incomplete.

Consensus-based recommendation 3.E15
Expert consensus	Level of consensus +++
If an expectant approach was chosen, progress should be monitored by transvaginal ultrasound examination within 7 to 14 days.

Consensus-based statement 3.S3
Expert consensus	Level of consensus +++
An additional transvaginal ultrasound examination may be carried out in the event of persistent menstrual-type bleeding, pain, or signs of infection during the miscarriage. Depending on the findings, a change in approach (drug-based, surgical) may be discussed with the patient.

Consensus-based recommendation 3.E16
Expert consensus	Level of consensus +++
In the event of a missed abortion, if bleeding has still not occurred, the patient should be offered another examination after 14 days at the latest as an alternative to changing the approach initially agreed upon.

Consensus-based recommendation 3.E17
Expert consensus	Level of consensus +
After a spontaneous abortion, Rh D-negative pregnant women must only receive anti-D prophylaxis if the gestational age is > 9 + 0 weeks of gestation.

Consensus-based recommendation 3.E18
Expert consensus	Level of consensus +++
Women must be informed about the variable course of bleeding and pain, the potential use of non-steroidal anti-inflammatory drugs for pain relief, and the possibility of another conception as well as necessary contraceptive measures, if required.

Consensus-based recommendation 3.E19
Expert consensus	Level of consensus +++
Women must not be advised to avoid tampons, menstruation cups, sexual intercourse, physical exertion or similar as the evidence for this is lacking.

Consensus-based recommendation 3.E20
Expert consensus	Level of consensus +++
The patient must be informed about typical symptoms such as noticeably long and severe persistent or foul-smelling bleeding and/or fever over 38 °C, which are indications for remaining residual tissue or infection.

2. Medication-based approach

Consensus-based recommendation 3.E21
Expert consensus	Level of consensus +++
Induction of miscarriage using medication should be carried out as an ambulatory procedure.

Consensus-based recommendation 3.E22
Expert consensus	Level of consensus +++
After receiving detailed information about the different types of approach, the patient must be able to make an informed decision about the preferred therapeutic approach.

Consensus-based recommendation 3.E23
Expert consensus	Level of consensus +++
The patient should be given information about the findings and treatment to take home with her and should be provided with an emergency telephone number.

Consensus-based recommendation 3.E24
Expert consensus	Level of consensus +++
The patient must be informed and educated about symptoms which occur during treatment and the signs of possible complications which require urgent treatment.

Consensus-based statement 3.S4
Expert consensus	Level of consensus +++
In cases with confirmed miscarriage (< 12th GW), the medication of choice to induce abortion should be a combination von 200 mg mifepristone taken orally followed by 600 – 800 µg misoprostol administered vaginally after 24 h.

Consensus-based recommendation 3.E25
Expert consensus	Level of consensus ++
If the first dose does not result in any discharge of tissue or only in insufficient discharge, a second dose of misoprostol should be taken at the earliest three hours after administration of the first dose.

Consensus-based statement 3.S5
Expert consensus	Level of consensus ++
Misoprostol may also be administered to women with previous caesarean section or any other transmural uterine scars.

Consensus-based recommendation 3.E26
Expert consensus	Level of consensus ++
Patients suffering a miscarriage must receive information about the three treatment options “medication to induce abortion”, “expectant management”, and “surgical procedure” and the information provided to the patient must be recorded.

Consensus-based recommendation 3.E27
Expert consensus	Level of consensus +++
With medication-based management, the patient must be informed about side effects and risks and about the off-label-use status of misoprostol. All information provided to the patient in this context must be recorded.

Consensus-based recommendation 3.E28
Expert consensus	Level of consensus +++
Antibiotic prophylaxis must not be administered if medication is used to induce abortion.

Consensus-based recommendation 3.E29
Expert consensus	Level of consensus +++
All contraindications must be considered and weighed up before the administration of medication to induce abortion.

Consensus-based recommendation 3.E30
Expert consensus	Level of consensus +++
Non-steroidal anti-inflammatory drugs, especially ibuprofen and oral metamizole, should be used to achieve adequate pain management.

Consensus-based recommendation 3.E31
Expert consensus	Level of consensus +++
An anti-emetic such as dimenhydrinate, metoclopramide, or ondansetron should be offered because of possible nausea and vomiting associated with the use of misoprostol.

Consensus-based statement 3.S6
Expert consensus	Level of consensus +++
If residual intrauterine tissue is suspected without relevant bleeding, management may consist of an expectant or medication-based approach, or vacuum aspiration may be used.

Consensus-based recommendation 3.E32
Expert consensus	Level of consensus +++
Surgical removal of retained products of conception must be carried out if persistent excessive menstruation-type vaginal or uterine bleeding occurs during medication-based induction of abortion and sonography shows residual tissue.

Consensus-based recommendation 3.E33
Expert consensus	Level of consensus +++
Any suspicion of ectopic or heterotopic pregnancy must be investigated using additional diagnostic measures.

Consensus-based recommendation 3.E34
Expert consensus	Level of consensus +++
Antibiotic therapy must be initiated immediately if there are any signs of infection.

Consensus-based recommendation 3.E35
Expert consensus	Level of consensus ++
All women who opt for medication-based induction of abortion must be advised to have a follow-up examination to confirm complete termination of the pregnancy. The follow-up examination must consist of transvaginal ultrasound carried out 7 to 14 days after taking the first dose of medication.

Consensus-based statement 3.S7
Expert consensus	Level of consensus ++
As part of follow-up care after medication-induced abortion, the patient may be offered contraception counseling, advice about the effect of the miscarriage on the patientʼs future fertility, and information about options which can support the patient to cope with the psychological effect of the pregnancy loss.

Consensus-based recommendation 3.E36
Expert consensus	Level of consensus ++
Womem who are Rh D-negative should receive an anti-Rh (D)-immunoglobulin dose within 72 hours after the first application of misoprostol during medication-induced abortion of a pregnancy of > 9 + 0 weeks of gestation (comfirmed gestational age).

3. Surgical approach

Consensus-based recommendation 3.E37
Expert consensus	Level of consensus +++
With surgical management, the patient must be informed about the risks compared to expectant and medication-based management, and the information provided must be documented.

Consensus-based recommendation 3.E38
Expert consensus	Level of consensus +++
The decision whether to carry out medication-based cervical ripening using a prostaglandin preparation or mechanical dilators should be taken on a case-by-case basis.

Consensus-based recommendation 3.E39
Expert consensus	Level of consensus +++
If misoprostol is administered to soften the cervix, the patient must be informed about its off-label use and the information provided to the patient must be documented.

Consensus-based statement 3.S8
Expert consensus	Level of consensus +++
Mifepristone/misoprostol may be considered for cervical priming in women who are status post caesarean section.

Consensus-based recommendation 3.E40
Expert consensus	Level of consensus +++
No antibiotic prophylaxis must be administered for abortion curettage.

Consensus-based recommendation 3.E41
Expert consensus	Level of consensus +++
Abortion curettage should be carried out as suction curettage/vacuum aspiration.

Consensus-based recommendation 3.E42
Expert consensus	Level of consensus +++
A control ultrasound examination may be carried out intraoperatively. If complications are suspected, a control ultrasound examination must be carried out.

Consensus-based recommendation 3.E43
Expert consensus	Level of consensus +++
The short duration of the procedure should be considered when choosing the anesthetic procedure.

Consensus-based recommendation 3.E44
Expert consensus	Level of consensus +++
Abortion curettage should be carried out as an ambulatory procedure. A stay in hospital may be required if there are medical, social, or logistical indications.

Consensus-based statement 3.S9
Expert consensus	Level of consensus +++
A low-dose combination of ibuprofen and paracetamol is very effective in patients. It has few side effects and may be considered as an alternative to monotherapy (in higher doses).

Consensus-based statement 3.S10
Expert consensus	Level of consensus +++
If the patient is experiencing moderate-to-severe pain, weak opioids such as tramadol (50 – 100 mg) maximum dose (400 – 600 mg/day) or tilidine (50 – 100 mg) maximum dose (400 – 600 mg/day) taken orally in combination with non-opioid analgesics may be administered (only to patients with no contraindications) to limit the use of opioids.

Consensus-based recommendation 3.E45
Expert consensus	Level of consensus ++
Anti-D-immunoglobulin prophylaxis should be offered to all Rh D-negative women who have undergone abortion curettage, irrespective of the gestational age of the pregnancy.

Consensus-based recommendation 3.E46
Expert consensus	Level of consensus +++
If the patient experiences severe postoperative bleeding, residual placental tissue must always be excluded as the cause.

Consensus-based statement 3.S11
Expert consensus	Level of consensus +++
If uterine perforation is suspected, laparoscopy may be carried out and surgical remediation if required.

Consensus-based recommendation 3.E47
Expert consensus	Level of consensus +++
Cervical injuries should be treated surgically.

Consensus-based recommendation 3.E48
Expert consensus	Level of consensus +++
If the miscarriage is a septic abortion, curettage must be carried out under antibiotic coverage.

Consensus-based recommendation 3.E49
Expert consensus	Level of consensus +++
If a pathological examination is requested, each embryo/fetus and all embryonic or fetal parts must be at least subjected to an external examination. Decidual tissue, chorionic villi, and embryonic tissue must be identified during macroscopic assessment of the abraded or expelled tissue. The assessment of the embryo must also record, if possible, the height, weight, crown-rump and foot length as well as any anomalies or malformations.

Consensus-based recommendation 3.E50
Expert consensus	Level of consensus +++
All aborted tissue should be subjected to histopathological examination.

Consensus-based recommendation 3.E51
Expert consensus	Level of consensus +++
The pathomorphological assessment of aborted tissue must include a statement on whether the pregnancy was an intrauterine or extrauterine pregnancy. The implantation site must be searched for if only individual chorionic villi can be detected. If no chorionic villi, implantation zone or trophoblast cells can be identified, all the submitted aborted fetal tissue must be embedded and examined microscopically.

Consensus-based recommendation 3.E52
Expert consensus	Level of consensus +++
The diagnostic assessment of the aborted fetal tissue must evaluate the pathophysiological changes and extent of any regressive postmortem changes to chorionic villi tissue based on the gestational age calculated and diagnosed on imaging.

Consensus-based recommendation 3.E53
Expert consensus	Level of consensus +++
Sequential β-HCG measurements must be carried out if the histological examination confirms the presence of a trophoblastic tumor.

Consensus-based recommendation 3.E54
Expert consensus	Level of consensus +++
Immunohistochemical p57 staining must be carried out to clearly differentiate between a partial molar pregnancy and a hydatidiform mole.

Consensus-based recommendation 3.E55
Expert consensus	Level of consensus +++
Immunohistochemical CD163 or CD68 staining must be carried out if chronic histiocytic intervillositis (CHI) is suspected.

Consensus-based recommendation 3.E56
Expert consensus	Level of consensus +++
Aborted fetal tissue should be given a dignified burial in accordance with the specific regulations in the respective German federal state, and the parents should be informed about the burial in an appropriate manner.

Consensus-based recommendation 3.E57
Expert consensus	Level of consensus +++
Women must be informed about the variable course of bleeding and pain, the use of non-steroidal anti-inflammatory medications for pain relief, and the possibility of conception.

Consensus-based recommendation 3.E58
Expert consensus	Level of consensus +++
The patient must not be advised to avoid the use of tampons, menstruation cups, sexual intercourse, and physical exertion as the evidence for this is lacking.

Consensus-based recommendation 3.E59
Expert consensus	Level of consensus ++
The patient must be informed about possible symptoms that are indications of residual retained products of conception or of infection.

Special situations

1. Incipient abortion

Consensus-based recommendation 4.E60
Expert consensus	Level of consensus +++
Bed rest must not be recommended for symptoms of incipient abortion.

Consensus-based recommendation 4.E61
Expert consensus	Level of consensus +
No progesterone preparations should be administered for symptoms of incipient miscarriage in the first trimester of pregnancy.

Consensus-based recommendation 4.E62
Expert consensus	Level of consensus +
Anti-D immunglobulin should not be administered for incipient miscarriage in the first trimester.

2. Approach for primary incomplete spontaneous abortion

Consensus-based recommendation 4.E63
Expert consensus	Level of consensus +++
Transvaginal sonography should be carried out if incomplete abortion is suspected. Doppler sonography may provide additional valuable information.

Consensus-based recommendation 4.E64
Expert consensus	Level of consensus +++
When incomplete abortion is suspected, all therapeutic options (expectant, medication, surgical) should be discussed with the patient in terms to the respective success rates and risks.

Consensus-based statement 4.S12
Expert consensus	Level of consensus +++
The approach for incomplete abortion can be expectant (up to 8 weeks) or consist of medication-based or surgical treatment.

3. Approach for septic abortion

Consensus-based recommendation 4.E65
Expert consensus	Level of consensus +++
If septic abortion is suspected, the necessary laboratory tests must be arranged on an emergency basis.

Consensus-based recommendation 4.E66
Expert consensus	Level of consensus +++
Treatment with broad-spectrum antibiotics must be initiated immediately for septic abortion.

Consensus-based recommendation 4.E67
Expert consensus	Level of consensus +++
If the patient is going through septic abortion with residual intrauterine tissue remnants, these residual products of conception must be removed surgically after the start of antibiotic therapy.

4. Approach for heterotopic pregnancy

Consensus-based recommendation 4.E68
Expert consensus	Level of consensus +++
When an intrauterine pregnancy has been confirmed by sonography, the adnexal regions must always be evaluated to exclude heterotopic pregnancy.

Consensus-based recommendation 4.E69
Expert consensus	Level of consensus +++
When choosing the appropriate treatment for a heterotopic pregnancy, the clinical situation and the vital intrauterine pregnancy must be considered.

5. Subsequent pregnancy after a miscarriage in the first trimester

Consensus-based statement 5.S13
Expert consensus	Level of consensus ++
After a miscarriage in the first trimester of pregnancy, the affected woman may be informed that she can become pregnant again without delay if there are no specific individual reasons not to do so. Reasons to postpone pregnancy can be: a diagnostic workup is necessary before becoming pregnant again, the affected woman is not yet ready psychologically, or the woman is still coping with the physical consequences of surgery.

Ectopic pregnancy

Consensus-based recommendation 6.E70
Expert consensus	Level of consensus +++
In principle, every sexually active women of child-bearing age should have a pregnancy test if abdominal pain occurs.

Consensus-based recommendation 6.E71
Expert consensus	Level of consensus +++
The patientʼs medical history and physical examination should always also consider the symptoms of persistent vaginal bleeding after previous secondary amenorrhea, pelvic and/or abdominal pain, and gastrointestinal complaints, especially diarrhea.

Consensus-based recommendation 6.E72
Expert consensus	Level of consensus +++
A diagnosis of ectopic pregnancy should not be based on the clinical examination and history alone, as the sensitivity of these factors is very limited.

Consensus-based recommendation 6.E73
Expert consensus	Level of consensus +++
In cases with symptomatic pregnancy of unclear localization, suspected ectopic pregnancy or miscarriage, quantitative serum/plasma hCG levels must be measured using an approved laboratory test.

Consensus-based recommendation 6.E74
Expert consensus	Level of consensus +++
Serum/plasma hCG concentrations must be determined during the examination.

Consensus-based recommendation 6.E75
Expert consensus	Level of consensus +++
The diagnosis of an ectopic pregnancy must include determination of serum β-hCG levels.

Consensus-based recommendation 6.E76
Expert consensus	Level of consensus +++
If the clinical situtation is unclear or management consists of an expectant approach, the β-hCG level must be checked after 48 h.

Consensus-based recommendation 6.E77
Expert consensus	Level of consensus +++
To diagnose symptomatic women, the method of choice to localize the pregnancy must be transvaginal sonography.

Consensus-based recommendation 6.E78
Expert consensus	Level of consensus +++
The aim of the diagnostic workup must be to identify and localize an ectopic pregnancy with sonography before potentially carrying out a surgical intervention.

Consensus-based recommendation 6.E79
Expert consensus	Level of consensus +++
The diagnostic and therapeutic method of choice for suspected acute or life-threatening bleeding ectopic pregnancy is emergency laparoscopy. The procedure must be carried out urgently without waiting for further diagnostic tests when managing a patient with a positive pregnancy test and presents with the clinical triad “unclear lower abdominal pain – hemodynamically problematic situation – low hemoglobin level.”

Treatment Options

1. Expectant approach

Consensus-based recommendation 6.E80
Expert consensus	Level of consensus +++
The patient must be informed about the possibility that the ectopic pregnancy may resolve itself and about the risks associated with expectant management, but it is not possible to provide her with precise information about the success rate and how long the resorption process will take.

Consensus-based recommendation 6.E81
Expert consensus	Level of consensus +++
It must be pointed out to the patient that although expectant management of a suspected tubal pregnancy may avoid methotrexate-related and anesthesia- and surgery-related risks, failure of expectant management may be associated with higher morbidity.

Consensus-based recommendation 6.E82
Expert consensus	Level of consensus +++
The patient must be informed that the effects of expectant management of ectopic pregnancy on future fertility will probably be similar to those occurring after treatment with methotrexate. But the data on this is not reliable.

Consensus-based statement 6.S14
Expert consensus	Level of consensus +++
Expectant management may be recommended to a hemodynamically stable and pain-free patient with sonographic indications of a non-vital tubal pregnancy with a maximum diameter of 35 mm, no signs of hemoperitoneum, and a maximum β-hCG concentration of 1000 IU/l.

Consensus-based recommendation 6.E83
Expert consensus	Level of consensus ++
If a patient with suspected tubal pregnancy opts for expectant management after she has been informed about all the risks, the requirements for her further care (compliance, carrying out close ambulantory monitoring) must be met.

Consensus-based recommendation 6.E84
Expert consensus	Level of consensus ++
During expectant management of a suspected ectopic pregnancy, control serum β-hCG measurements should be carried out on days 2, 4 and 7 after the initial diagnosis.

Consensus-based recommendation 6.E85
Expert consensus	Level of consensus +++
If the β-hCG levels on days 2, 4 and 7 have decreased by 15% or more each time compared to the previous level, the laboratory tests must be repeated every 7 days until the β-hCG level is no longer detectable in serum.

Consensus-based recommendation 6.E86
Expert consensus	Level of consensus +++
If the β-hCG level does not decrease by 15%, does not change, or increases compared to previously measured concentrations, the patientʼs condition must be critically reviewed clinically and sonographically, and the decision for expectant management must be revisited.

Consensus-based recommendation 6.E87
Expert consensus	Level of consensus +++
Surgery is indicated after a previous decision for expectant management if one or more of the following criteria are met: Patient has clinical symptoms; Signs of tubal rupture and/or intraperitoneal bleeding, Hemoperitoneum (Hb concentration < 10 g/dl); Diameter has increased (size progression) to more than 35 mm and/or fetal heartbeat is detectable during transvaginal ultrasound examination; β-hCG level has risen to more than 1000 IU/l; Patient is not sufficiently compliant; Patient cannot obtain care close to home and there is a lack of willingness on the part of the patient to comply with required monitoring of her progress including regular repeat visits for clinical and sonographic examination and blood tests.

Consensus-based recommendation 6.E88
Expert consensus	Level of consensus +++
Because of the risk of Rh D alloimmunization during expectant management in non-sensitized Rh D-negative women with suspected ectopic pregnancy, these patients should be offered anti-D prophylaxis.

2. Medication-based therapy

Consensus-based recommendation 6.E89
Expert consensus	Level of consensus +++
All contraindications must be excluded before starting a patient on methotrexate therapy for ectopic pregnancy.

Consensus-based recommendation 6.E90
Expert consensus	Level of consensus +++
During methotrexate therapy for suspected ectopic pregnancy, the serum β-hCG concentration must be checked at regular intervals until β-hCG can no longer be detected.

Consensus-based recommendation 6.E91
Expert consensus	Level of consensus +++
Patients must be informed in detail about the nature of the off-label use of methotrexate therapy and the information must be documented in writing.

Consensus-based recommendation 6.E92
Expert consensus	Level of consensus +++
The patient should be informed about the suspected diagnosis, the possible consequences of methotrexate therapy, and the different treatment options available. If possible, the treatment path should be decided on using a joint decision-making process.

Consensus-based recommendation 6.E93
Expert consensus	Level of consensus +++
If there are no contraindications, medication-based treatment of an ectopic pregnancy should consist of a single intramuscular injection of methotrexate administered at a dose of 1 mg/kg body weight or 50 mg/m2 body surface.

Consensus-based recommendation 6.E94
Expert consensus	Level of consensus +++
Specific laboratory tests (complete blood count with differential blood count, liver enzymes (ALT [GPT], AST [SGOT], ALP), GGT, bilirubin, serum albumin, hepatitis serology, renal retention parameters) should be carried out before every administration of methotrexate.

Consensus-based recommendation 6.E95
Expert consensus	Level of consensus ++
Women should be advised to use a reliable contraceptive method for six months after completing methotrexate therapy.

Consensus-based recommendation 6.E96
Expert consensus	Level of consensus ++
Medication-based treatment for ectopic pregnancy should be carried out on an outpatient basis.

Consensus-based recommendation 6.E97
Expert consensus	Level of consensus +++
Surgery must be carried out if an ectopic pregnancy is suspected and methotrexate therapy is absolutely contraindicated.

Consensus-based recommendation 6.E98
Expert consensus	Level of consensus +++
Surgery must be carried out if an ectopic pregnancy is suspected and medication-based treatment has failed.

Consensus-based recommendation 6.E99
Expert consensus	Level of consensus +++
All Rhesus-negative women receiving medication to treat an extrauterine pregnancy should be given anti-D prophylaxis.

3. Surgical approach

Consensus-based statement 7.S15
Expert consensus	Level of consensus +++
A laparoscopic approach is the method of choice if the decision is taken to carry out surgery based on a (suspected) diagnosis of tubal pregnancy.

Consensus-based recommendation 7.E100
Expert consensus	Level of consensus +++
Even if tubal pregnancy is suspected and the patient is hemodynamically unstable, the next diagnostic and therapeutic step must consist of exploratory laparoscopy.

Consensus-based recommendation 7.E101
Expert consensus	Level of consensus +++
The decision whether to carry out salpingectomy or to preserve the fallopian tube must depend on the clinical situation, the patientʼs medical history, and the patientʼs wishes.

Consensus-based statement 7.S16
Expert consensus	Level of consensus +++
Vacuum extraction/curettage may be carried out at the same time if an ectopic pregnancy is suspected, the intraabdominal laparoscopic findings to confirm the pregnancy are unclear, and the increase in serum β-hCG levels was insufficient.

Consensus-based recommendation 7.E102
Expert consensus	Level of consensus +++
Postoperative monitoring of β-hCG concentrations must be carried out if surgery was a tube-sparing procedure.

Consensus-based recommendation 7.E103
Expert consensus	Level of consensus +++
RhD-negative women who undergo surgery for tubal pregnancy should be given anti-D prophylaxis.

Consensus-based recommendation 7.E104
Expert consensus	Level of consensus +++
No antibiotic prophylaxis must be administered during laparoscopic therapy of a tubal pregnancy.

Approach for rare forms of ectopic pregnancy

1. Cervical pregnancy

Consensus-based recommendation 7.E105
Expert consensus	Level of consensus +++
A cervical pregnancy must be confirmed as early as possible.

Consensus-based recommendation 7.E106
Expert consensus	Level of consensus +++
Transvaginal sonography must be carried out as the first-choice diagnostic procedure if there is a clinical suspicion of cervical pregnancy.

Consensus-based recommendation 7.E107
Expert consensus	Level of consensus +++
The preferred option to treat cervical pregnancy diagnosed in its early stages should be intramuscular administration of methotrexate.

2. Caesarean scar pregnancy

Consensus-based recommendation 7.E108
Expert consensus	Level of consensus +++
Transvaginal sonography must be carried out in early pregnancy to locate the site of pregnancy in women who have previously had a caesarean section.

Consensus-based recommendation 7.E109
Expert consensus	Level of consensus +++
When making the diagnosis, a caesarean scar pregnancy should be treated as early as possible (ideally before 8 + 0 GW) as treatment success rates decrease and complication rates increase with advancing gestational age.

Consensus-based recommendation 7.E110
Expert consensus	Level of consensus +++
Treatment of a caesarean scar pregnancy should not only consist of administering systemic methotrexate.

3. Cornual ectopic pregnancy

Consensus-based statement 7.S17
Expert consensus	Level of consensus +++
3D ultrasound examination may be useful to show the general uterine anatomy and the location of the ectopic pregnancy, in particular.

Consensus-based recommendation 7.E111
Expert consensus	Level of consensus +++
If implantation occurs in a rudimentary uterine horn, the treatment of choice should consist of the surgical removal of the complete rudimentary uterine horn and the proximal uterine tube.

Consensus-based recommendation 7.E112
Expert consensus	Level of consensus +++
An expectant approach to treat interstitial pregnancy should only be discussed if the pregnancy is not viable and the β-hCG levels are decreasing and only after the patient has been explicitly informed about the risks.

Consensus-based recommendation 7.E113
Expert consensus	Level of consensus +++
Treatment for an interstitial pregnancy should consist of surgical intervention as it is the most effective therapeutic approach. A medication-based approach using methotrexate (systemic/local) may be considered for carefully selected patients.

4. Ovarian pregnancy

Consensus-based recommendation 7.E114
Expert consensus	Level of consensus ++
If ovarian pregnancy is suspected, laparoscopy must be the first-choice method to confirm the suspected diagnosis and carry out definitive therapy.

Consensus-based recommendation 7.E115
Expert consensus	Level of consensus +++
If ovarian pregnancy is suspected, surgical intervention should be carried out at an early stage because of the high risk of hemorrhage.

Consensus-based recommendation 7.E116
Expert consensus	Level of consensus +++
When carrying out surgery for an ovarian pregnancy, the aim should be to preserve the ovary (cyst enucleation or wedge resection).

Consensus-based recommendation 7.E117
Expert consensus	Level of consensus ++
If ovarian pregnancy is suspected, methotrexate may be considered as an alternative first-line treatment and should be considered as an alternative second-line approach.

5. Abdominal pregnancy

Consensus-based statement 7.S18
Expert consensus	Level of consensus +++
An early abdominal pregnancy may be treated using laparoscopy.

Consensus-based recommendation 7.E118
Expert consensus	Level of consensus +++
An advanced abdominal pregnancy should be treated using laparotomy, preferably using longitudinal laparotomy.

Consensus-based recommendation 7.E119
Expert consensus	Level of consensus +++
With an abdominal pregnancy, complete extraction of the placenta after individual assessment of the maternal morbidity risk must only be carried out if it can be carried out easily and the risk of hemorrhage is low.

Psychological aspects in early loss of pregnancy

Consensus-based recommendation 8.E120
Expert consensus	Level of consensus +++
Women should be directly addressed to see how they are coping psychologically with their pregnancy loss and should be actively offered support.

Consensus-based recommendation 8.E121
Expert consensus	Level of consensus +++
To provide positive support during the grieving process, the patient should be advised with empathy. The advice should be adapted to the specific situation and should be unbiased so that the patient is able to make a decision afterwards about her further treatment together with the doctors treating her.

Consensus-based recommendation 8.E122
Expert consensus	Level of consensus +++
The information, education, support, and medical care provided to vulnerable patients requires particular sensitivity and professionality. The patient should be informed about the available non-medical support, if necessary, in cooperation with professionals working in other specialized medical areas.

Consensus-based recommendation 8.E123
Expert consensus	Level of consensus +++
Women with an early loss of pregnancy and, if necessary, their partner should be advised that as with other serious life events, they may experience a wide range of grief responses and feelings of loss and guilt, which are not initially a sign of a mental disorder.

Consensus-based recommendation 8.E124
Expert consensus	Level of consensus +++
The medical staff involved in the care and treatment of women with early loss of pregnancy should respond supportively and empathetically to the emotional reactions of women who have experienced an early loss of pregnancy.

Consensus-based recommendation 8.E125
Expert consensus	Level of consensus +++
After an early loss of pregnancy, women and, if necessary, their partner should be encouraged to seek support from suitable persons in their social community.

Consensus-based recommendation 8.E126
Expert consensus	Level of consensus +++
After an early loss of pregnancy, women with the above-mentioned risk factors or clearly suffering from psychological stress should be provided with information about follow-up care services and psychological counseling.

Consensus-based recommendation 8.E127
Expert consensus	Level of consensus +++
After an early pregnancy loss, women with known psychological problems should be asked whether they wish to have psychotherapeutic or psychiatric support and whether they will be able to address possible problems related to the pregnancy loss in therapy. If necessary, they should be informed about specific (additional) support services.

Consensus-based statement 8.S19
Expert consensus	Level of consensus +++
From about six weeks after the early loss of pregnancy, the physician may assess the patient for depressive symptoms, e.g., using the two-question Patient Health Questionnaire (PHQ-2).

Consensus-based recommendation 8.E128
Expert consensus	Level of consensus +++
Women who report relevant psychological symptoms more than two months after the pregnancy loss should be advised to have a psychiatric assessment and treatment, if necessary.

Consensus-based recommendation 8.E129
Expert consensus	Level of consensus +++
Following an early pregnancy loss, both partners should be asked about their mental stress to reduce the possible negative impact on their partnership and sexuality.

The detailed list of references is available in the German-language long version of the guideline.

Conflict of Interest

The conflicts of interest of the authors are listed in the German-language long version of the guideline.

• References/Literatur

• 1 American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 200: Early Pregnancy Loss. Obstet Gynecol 2018; 132: e197-e207
• 2 Al Wattar BH, Murugesu N, Tobias A. et al. Management of first-trimester miscarriage: a systematic review and network meta-analysis. Hum Reprod Update 2019; 25: 362-374
• 3 Dhillon-Smith RK, Melo P, Devall AJ. et al. A core outcome set for trials in miscarriage management and prevention: An international consensus development study. BJOG 2023; 130: 1346-1354
• 4 Musik T, Grimm J, Juhasz-Böss I. et al. Treatment Options After a Diagnosis of Early Miscarriage: Expectant, Medical, and Surgical. Dtsch Arztebl Int 2021; 118: 789-794

Publication History

Received: 08 November 2024

Accepted: 10 November 2024

Article published online:
05 March 2025