Threatened Abortion

Dhirapatara Charoenvidhya,MD
Maternal-Fetal Medicine division,
Department of Obstetrics and Gynecology ,
Faculty of Medicine, Chulalongkorn University
Outlines
1. Definition
2. Etiology
3. Pathophysiology
4. Evaluation
5. adverse pregnancy outcomes
6. management of threatened abortion
Definition
• Vaginal bleeding in the presence of a closed cervix
and sonographic visualization of an intrauterine
pregnancy with detectable fetal cardiac activity
• Vaginal bleeding
• Closed cervix
• USG à intrauterine pregnancy + fetal cardiac activity

UpToDate 2021
Definition
• The definition of a threatened abortion by the
World Health Organization (WHO) is pregnancy-
related bloody vaginal discharge or frank bleeding
during the first half of pregnancy without
cervical dilatation
Definition
• The term "threatened" is used to describe these
cases because early pregnancy loss does not
always follow vaginal bleeding.
• 90 - 96 % of pregnancies with both fetal cardiac
activity and vaginal bleeding at 7 to 11 weeks of
gestation are not lost.

UpToDate 2021
Etiology
• The exact etiology of a threatened or spontaneous
abortion is not always known.
• Some factors such as
• Fetal chromosome abnormalities
• Maternal diseases Ex: DM, HT ,chronic kidney disease
• Advanced maternal age
May associated with
• Uterine anomalies Threaten abortion
• Hormonal deficit
• Infection
• Etc.

Mouri M, Hall H, Rupp TJ. Threatened Abortion. 2021 May 19. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–. PMID: 28613498.
Pathophysiology
Generally cannot be
visualized by
ultrasound
Vaginal
Bleeding

a subchorionic
hematoma

disruption of decidual
vessels at the maternal-
fetal interface

UpToDate 2021
Luteal phase defect (LPD)
• LPD is considered to be one of the causes of a
euploid miscarriage.
• The corpus luteum in the ovary produces
progesterone during early pregnancy.
• Progesterone is essential for maintaining the
decidua.
Luteal phase defect (LPD)

a defect in
the low increase the
function of progesterone risk of
the corpus levels miscarriage.
luteum
Luteal phase defect (LPD)
• there is no clear definition for LPD.
• there are certainly no reliable tests to identify
patients who may have the condition.
• Serum progesterone remained unclear.
• salivary progesterone
Evaluation
• History à Preg Hx, Medical Hx, present illness
• Physical exam à vaginal and pelvic examination
• measurement of beta-human chorionic
gonadotropin (beta-hCG)
• A beta-hCG level of 1500 lU/mL to 2000 lU/mL à
Gestational sac on ultrasound
• TVS à locate the pregnancy + fetal cardiac activity
• Hb and Hct à monitor blood loss
• Rh blood group -- > Rhogram in Rh negative
mother
Mouri M, Hall H, Rupp TJ. Threatened Abortion. 2021 May 19. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–. PMID: 28613498.
Adverse pregnancy outcomes
(increased in threaten abortion)
Maternal outcomes Perinatal outcomes

Placenta previa Preterm ruptured membranes

Placental abruption Preterm birth

Manual removal of placenta Low-birthweight infant

Cesarean delivery Fetal-growth restriction

Fetal and neonatal death

William Obstetrics 25th edition 2018

Management of threatened
abortion
• Expectantly without any medical or surgical
interventions.
• Patients should be educated on the importance of
follow-up if
• excessive vaginal bleeding
• Abdominal pain
• Fever
• Analgesia can be provided (NSAIDs should be
avoided)

Mouri M, Hall H, Rupp TJ. Threatened Abortion. 2021 May 19. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–. PMID: 28613498.
Management of threatened
abortion
• Follow-up is recommended with serial transvaginal
ultrasounds
• Clinicians can consider serial quantitative beta hCG
testing as recommended for a pregnancy of
unknown origin.
• Bedrest and other activity restrictions
• à not been found to be efficacious in the prevention
• à increase the risk of deep vein thrombosis and/or
pulmonary embolism

Mouri M, Hall H, Rupp TJ. Threatened Abortion. 2021 May 19. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–. PMID: 28613498.
Management of threatened
abortion
• Clinicians should recommend patients that start or
continue to take prenatal vitamins with folic acid
supplementation.

Mouri M, Hall H, Rupp TJ. Threatened Abortion. 2021 May 19. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–. PMID: 28613498.
Management of threatened
abortion
• How about Progesterone ?????

Mouri M, Hall H, Rupp TJ. Threatened Abortion. 2021 May 19. In: StatPearls
[Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–. PMID: 28613498.
PRISM trial (PRogesterone In Spontaneous Miscarriage trial)
n engl j med 380;19 nejm.org May 9, 2019
400 mg of micronized progesterone
(Utrogestan, Besins Healthcare) or
matching placebo twice daily, from
the time of randomization through
16 completed weeks of gestation
Coomarasamy et al. Micronized vaginal progesterone to prevent miscarriage: a
critical evaluation of randomized evidence. Am J Obstet Gynecol 2020.
Number of previous miscarriage >= 3 Risk ratio 1.28 (1.08-1.51)
PRISM trial
Random-effects meta-analysis of progesterone on live birth events,
stratified by oral and vaginal progesterone.
Random-effects meta-analysis of progesterone on miscarriage events, stratified by oral and
vaginal progesterone.
Devall AJ, Papadopoulou A, Podesek M, Haas DM, Price MJ, Coomarasamy A,
Gallos ID. Progestogens for preventing miscarriage: a network meta-analysis.
Cochrane Database of Systematic Reviews 2021
Authors' conclusions
• The overall available evidence suggests that
progestogens probably make little or no difference
to live birth rate for women with threatened or
recurrent miscarriage.
• Vaginal micronized progesterone may increase the
live birth rate for women with a history of one or
more previous miscarriages and early pregnancy
bleeding, with likely no difference in adverse
events.
International guidelines:
Miscarriage
 GUIDELINES RECOMMENDATIONS ON TM
European Progestin Club For women presenting with a clinical diagnosis of TM, there is a reduction in
the rate of spontaneous miscarriage with the use of dydrogesterone. 1
Guidelines 2015
Progestogen supplementation until the second trimester in women presenting
with a clinical diagnosis of threatened miscarriage may reduce the rate of
RANZCOG spontaneous miscarriage and may be considered. 2
2018
Treatment of miscarriage with progestogens compared to placebo or no
treatment probably reduces the risk of miscarriage. Treatment with oral
2018 progestogen compared to no treatment also probably reduces the miscarriage
rate.3
Data from a meta-analysis of several small studies suggest that progestogens
2019 are better than placebo. 4

TM: Threatened miscarriage; RM: Recurrent miscarriage; RPL: Recurrent pregnancy loss
1. Schindler AE, Carp H, Druckmann R, et al. European Progestin Club Guidelines for prevention and treatment of threatened or recurrent (habitual) miscarriage with progestogens.
Gynecol Endocrinol 2015;31(6):447–449.
2. Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG). Progesterone support of the luteal phase and in the first trimester (C-Obs 29a). March 2018.
http://www.ranzcog.edu.au/component/docman/doc_details/961-c-obs-29a-progesterone-support-of-the-luteal-phase-and-early-pregnancy.html?Itemid=223l. Accessed August 2016.
3. Wahabi HA, Fayed AA, Esmaeil SA, Al Zeidan RA. Progestogen for treating threatened miscarriage. Cochrane Database Syst Rev 2018;(8):CD005943.
4. National Institute for Health and Care Excellence (NICE). Ectopic pregnancy and miscarriage: diagnosis and initial management. (NG126) Published April 2019.
www.nice.org.uk/guidance/ng126 . Accessed Aug 2020
 GUIDELINES RECOMMENDATIONS ON TM
Oral progestogens, namely dydrogesterone, are well-tolerated &
Saudi Guidelines 2020 effectively reduce miscarriages in women at risk of TM. 1
1. In patient without prior history of miscarriage, oral
dydrogesterone can be considered, from onset of bleeding till 1
Malaysia 2020
week after bleeding has stopped
2. In women with a history of ≥1 previous miscarriage,
dydrogesterone 10 mg BD from the onset of bleeding up till 16
weeks of pregnancy may be considered.
China 2021 3. Dydrogesterone may be associated with fewer side effects than
oral micronized progesterone. 2
Oral progesterone is preferred. 1st line treatment: Dydrogesterone
40mg PO stat followed by 10 mg q8h until symptom remits, then U/S
to confirm fetal heart beat. Thereafter, Dydrogesterone 10mg q8 h to
be continued for 1~2 weeks. 3

TM: Threatened miscarriage; BD: Twice daily; PO: per oral route; U/S: Ultra sounds; q8h: per 8 hours.
1. Arab H, Alharbi AJ, Oraif A, et al. The Role Of Progestogens In Threatened And Idiopathic Recurrent Miscarriage. Int J Womens Health. 2020; Apr 08;12:253].
International Journal of Women's Health 2019:11:589–596;
2. Eeson Sinthamoney et al., OGSM 12 May 2020 https://www.ogsm.org.my/docs/Clinical-Practice-Guidelines-on-Miscarriage-Management.pdf;
3. Qiao Jie et al., Chin J Reprod Contracep, February 2021, Vol. 41, No. 2
Conclusions
Treatment Recommendation

Expectant management Recommended

Analgesia Avoid NSAIDs Recommended

Follow up ultrasound Recommended

serial quantitative beta For pregnancy of Recommended

hCG testing unknown location
Bedrest and other Increased risk of DVT Not Recommended
activity restrictions
prenatal vitamins with Recommended
folic acid
supplementation.
Conclusions
Treatment Route Recommendation

Progesterone Oral dydrogesterone Some recommended

Vaginal micronized Recommended

progesterone (a history of one or more
previous miscarriages)

17-α- Not Recommended

hydroxyprogesterone (no evidence)

Oral micronized Not Recommended

progesterone (no evidence)