Table 1.

Summary of guidelines for treatment of pregnancy loss.

Guidelines for Threatened PL
International and Regional Guidelines/Citation	Recommendations/Statements
EPC guideline (2015 [5])	For women presenting with a clinical diagnosis of threatened PL, there is a reduction in the rate of spontaneous PL with the use of dydrogesterone
Australia and New Zealand, RANZCOG guidelines [25]	Progestogen supplementation until the second trimester in women presenting with a clinical diagnosis of threatened miscarriage may reduce the rate of spontaneous miscarriage and may be considered
National Guideline/Citation	Recommendations/Statements
UK, NICE guidelines [26]	Offer vaginal micronized progesterone 400 mg BID to women with an intrauterine pregnancy confirmed by a scan if they have vaginal bleeding and have previously had a miscarriage
Saudi Arabian guidelines [27]	Oral progestogens, namely dydrogesterone, are well tolerated and effectively reduce miscarriages in women at risk of threatened miscarriage
	Available evidence is insufficient to recommend the use of vaginal progestogens a for the treatment of threatened miscarriage
Russian clinical guidelines (miscarriage) [28]	Dydrogesterone or micronized progesterone should be prescribed to women with threatened miscarriage as a pregnancy-saving therapy. Both dydrogesterone and micronized progesterone have good safety profiles
Malaysian guidelines [29]	Women may be treated with: Oral dydrogesterone (10 mg BID), from the onset of bleeding until 1 week after bleeding has stopped Oral dydrogesterone (10 mg BID from the onset of bleeding until the 16th week of pregnancy), or micronized progesterone (400 mg BID vaginal/rectal administration) if the woman has a history of ≥1 previous miscarriage
FOGSI guidelines [30]	Women may be treated with MVP (400 mg/day until bleeding stops) or oral dydrogesterone (40 mg loading dose followed by 20–30 mg/day until 7 days after bleeding stops)
Chinese guidelines [31]	Oral dydrogesterone is the first choice—40 mg immediately, followed by 10 mg every 8 h until symptoms abate; then continue oral dydrogesterone for 1 to 2 weeks
Vietnamese guidelines [32]	Endocrine medication, such as progesterone 25 mg × 2 ampoules (intramuscular injection)/day, if there is evidence of endocrine insufficiency or to relax the uterine muscles
Vietnamese Hung Vuong Hospital guidelines [33]	Treat symptoms after excluding infectious threatened miscarriage: Progesterone 25 mg/ampoule (intramuscular injection); 1–4 ampoules/day Semi-synthetic (dydrogesterone), maximum dose 40 mg/day; Oral progesterone, maximum dose 600 mg/day
Taiwanese guidelines, Taiwan Society of Perinatology 2022 [34]	Oral dydrogesterone is the only recommended medicine: 40 mg immediately followed by 10 mg BID until symptoms are in complete remission; then continue dydrogesterone 10 mg BID for 1 to 2 weeks
Indonesian guidelines [35]	Natural progestogens can be used as therapy for threatened miscarriage Recommendations for treatment include: Dydrogesterone initial dose of 40 mg orally followed by 3 × 10 mg until bleeding stops. Then taper off 2 × 10 mg up to 16 weeks gestation Progesterone 2 × 400 mg orally until 12 weeks gestation Pessary progesterone 2 × 400 mg rectally Progesterone gel 8%, 90 mg, 1–2 times/day vaginally Hydroxyprogesterone 250 mg/week, intramuscularly
Mexican guidelines [36]	Current evidence is insufficient for prescribing progesterone; however, the use of progesterone is recommended for avoiding an emergency and unnecessary medical procedure, and for reassuring the patient
Philippines [37]	Data are limited and further investigation is required; however, there is some evidence that progesterone treatment may reduce the risk of a PL even in women without a history of recurrent PL Progesterone is available for use in three forms: oral, intramuscular, and intravaginal. Among these preparations, oral progesterone is more effective for the treatment of women with threatened PL Progesterone, especially oral dydrogesterone, may be given to treat threatened PL in women with a history of recurrent PL
Guidelines for Recurrent PL
International and Regional Guidelines/Citation	Recommendations/Statements
EPC guideline [5]	For women presenting with a clinical diagnosis of recurrent miscarriage (three or more), there is a reduction in the rate of miscarriage with the use of dydrogesterone
ESHRE guideline [7]	Vaginal progesterone during early pregnancy has no beneficial effect in women with unexplained recurrent PL. There is some evidence that dydrogesterone, initiated when fetal heart action can be confirmed, may be effective, but more trials are needed
German (DGGG), Austrian (OEGGG), and Swiss (SGGG) Societies of Gynecology and Obstetrics guideline [10]	Synthetic progestogens b can be administered to women with idiopathic recurrent miscarriage in the first trimester of pregnancy to prevent miscarriage
	Treatment with natural micronized progesterone in the first trimester of pregnancy to prevent miscarriage is not recommended for women with idiopathic recurrent miscarriage
National Guideline/Citation	Recommendations/Statements
UK, Royal College of Obstetricians and Gynaecologists guidelines [11]	There is insufficient evidence to evaluate the effect of progesterone supplementation in pregnancy to prevent a miscarriage in women with recurrent miscarriage
American Society for Reproductive Medicine [8]	In patients with three or more consecutive miscarriages immediately preceding their current pregnancy, empiric progestogen administration may be of some benefit
Saudi Arabian guidelines [27]	Oral progestogens, namely dydrogesterone, are well tolerated and effectively reduce miscarriages in women at risk of idiopathic recurrent miscarriage
	Available evidence is insufficient to recommend the use of vaginal progestogens a for the treatment of recurrent miscarriage
Israeli guidelines [38]	Progesterone support has been found to provide an advantage in women with recurrent PLs. Meta-analyses and systematic reviews have found an advantage in specific preparations such as dydrogesterone
Russian clinical guidelines (recurrent miscarriage) [39]	Dydrogesterone or micronized progesterone should be prescribed to women with recurrent miscarriage before pregnancy in luteal phase or from the first visit during pregnancy until 20 weeks of pregnancy. Both dydrogesterone and micronized progesterone have good safety profiles
Russian clinical guidelines (normal pregnancy) [40]	Oral dydrogesterone (20 mg/day) or micronized progesterone (200–600 mg/day, oral or vaginal) should be prescribed to women with recurrent miscarriage from the first visit until 20 weeks of pregnancy
Malaysian guidelines [29]	Can consider progesterone therapy in women with unexplained recurrent miscarriages: There is some evidence that oral dydrogesterone is effective if initiated when fetal heart activity is confirmed
FOGSI guidelines [30]	Women may be treated with oral dydrogesterone (10 mg BID until 20 weeks of pregnancy) or MVP (400 mg/day until 20 weeks of pregnancy)
Chinese guidelines [31]	Oral dydrogesterone is the first choice: 30 mg/day
Taiwanese guidelines, Taiwan Society of Perinatology 2022 [34]	Oral dydrogesterone 10 mg BID or MVP 400 mg BID is to be given when pregnancy is confirmed. Treatment should be continued until 20th week of gestation
Indonesian guidelines [41]	Administration of dydrogesterone significantly reduces the chance of recurrent miscarriage and increases pregnancy rate (Recommendation A) Administration of dydrogesterone is more effective and beneficial when started as soon as fetal heart activity is confirmed/from the luteal phase, because it has been shown to reduce the risk of miscarriage (Recommendation A)
Vietnamese guidelines [32]	Treatment option is based on the cause of recurrent miscarriage; in the case of endocrine insufficiency: endocrine supplements such as progesterone 25 mg × 2 ampoules (deep intramuscular injection)/day, estrogen 2 mg/day
Philippines [37]	There appears to be benefit in giving progestogens orally (medroxyprogesterone acetate 10 mg/day or dydrogesterone 20–30 mg/day until ≥12 weeks) or intramuscularly (hydroxyprogesterone caproate 500 mg/week until 36 weeks) in preventing PL among women who have a history of recurrent PL There is insufficient evidence to show any preferred route, dosage, or duration of treatment

^a Capsule, suppository, micronized, or gel; ^b supporting dataset included dydrogesterone in the synthetic progestogen group [42]. BID, twice daily; EPC, European Progestin Club; ESHRE, European Society of Human Reproduction and Embryology; FOGSI, Federation of Obstetric and Gynaecological Societies of India; MVP, micronized vaginal progesterone; NICE, National Institute for Health and Care Excellence; PL, pregnancy loss; RANZCOG, Royal Australian and New Zealand College of Obstetricians and Gynaecologists; UK, United Kingdom.