. 2012 Jul 16;28(12):983–990. doi: 10.3109/09513590.2012.702875

Table II. .

Long term follow-up data.

Author	Design/Indication	Sample size	Regimen	Outcome	Side Effects/AEs
Randomized studies
Ehrenskjöld et al [11]	Double-blind, placebo-controlled/threatened miscarriage	72 pts	DYD,	14 miscarriages or stillbirths,	No birth defects,
		72 pts	strict bed rest	58 live births (3 twins)	no side effects
		81 pts	Placebo,	23 miscarriages or stillbirths,	1 x hip dislocation,
		81 pts	strict bed rest	58 live births (1 twin)	1 x coarctation of the aorta
Mistò [12]	Double-blind, placebo-controlled/threatened miscarriage	7 pts	DYD	7 births	No signs of masculinization
Mistò [12]	Double-blind, placebo-controlled/threatened miscarriage	9 pts	placebo	7 births and 2 abortive interrup-tions of pregnancy
El-Zibdeh and Yousef [13]	Open-label, randomized/threatened miscarriage, viable fetus	86 pts	DYD + standard supportive care	65 deliveries, 6 preterm labors, 15 miscarriages.	No AEs, 1 neural tube defect, 1 heart disease
El-Zibdeh and Yousef [13]	Open-label, randomized/threatened miscarriage, viable fetus	60 pts	Standard supportive care alone	40 full-term deliveries, 5 preterm labor, 15 miscarriages (25%).	1 neural tube defect, 1 unspecified abnormality
Omar et al. [14]	Open-label, randomized/threatened miscarriage in first trimester, viable fetus	74 pts	DYD, bed rest, folic acid	71 pregnancies continued >Week 20, 3 miscarriages.	Safety and tolerability not reported.
Omar et al. [14]		80 pts	Bed rest, folic acid	69 pregnancies continued >Week 20; 11 miscarriages
Pandian [15]	Open-label, randomized/threatened miscarriage, viable fetus, <Week 16	96 pts	DYD	84 pregnancies continued >Week 20, 12 miscarriages	No intrauterine deaths or congenital abnormalities. 3 (3.1%) low birth weight (<2.500 g) infants.
Pandian [15]		95 pts	Bed rest	68 pregnancies continued >Week 20, 27 miscarriages	No intrauterine deaths or congenital abnormalities. 2 (2.1%) low birth weight (<2.500 g) infants
Czajkowski et al. [10]	Double-blind randomized/threatened miscarriage, <12 weeks, viable embryo	24 pts	DYD	2 miscarriages; 8%	Safety and tolerability data not reported.
Czajkowski et al. [10]		29 pts	Vaginal progesterone	4 abortions; 14%
Vincze et al. [16]	Open-label, randomized/threatened miscarriage,	86 pts	DYD	7 abortions	No side effects. No fetal abnormalities in either group.
Vincze et al. [16]	Week 5–13 of gestation	63 pts	Micronized progesterone (vaginal)	5 miscarriages
Open-label studies, non-randomized
Bashmakova et al. [17]	Open, cohort/Threatened miscarriage in first trimester.	275 pts	DYD plus standard therapy	10% premature births (p < 0.05), 29% healthy (not significant)	DYD: higher birth weight (3,350 ± 62g vs. 3,137 ± 93 g; higher 1 minute Apgar score (7.15 ± 0.98 vs. 6.8 ± 0.18; less hypoxic-ischemic CNS lesions (9% vs. 29%; less requirement for rehabilitation in the pediatric clinic (26% vs. 44%). All p < 0.05.
Bashmakova et al. [17]	Open, cohort/Threatened miscarriage in first trimester.	45 pts	Standard therapy alone	20% preterm births, 18% healthy
Kalinka and Szekeres-Bartho [19]; Kalinka and Radwan [20]	Threatened miscarriage	27 pts	DYD	3 missed miscarriages; 11.1% (2 deliveries preterm)	No significant differences between groups for mean gestational age or birth weight.
Kalinka and Szekeres-Bartho [19]; Kalinka and Radwan [20]	Threatened miscarriage	16 normal pregnant women	No treatment	1 missed miscarriage; 6.3% (no preterm delivery)
Manukhin, et al. [21]	Open-label/threatened miscarriage	45 pts	DYD plus standard care	Pregnancy progressed in 43 pts; 95.6% (difference vs. control group statistically significant)	Safety and tolerability data not reported.
Manukhin, et al. [21]	Open-label/threatened miscarriage	41 pts	“Symptomatic treatment” only,	Pregnancy progressed in 22 pts; 53.7%
Pelinescu-Onciul [22],	Open-label/threatened miscarriage, viable fetus	100 pts	DYD	Pregnancy progressed in 93 pts.	Only side effect reported with DYD was drowsiness
		100 pts	DYD	7 miscarriages (p = 0.002 vs. vaginal progesterone)	Only side effect reported with DYD was drowsiness
		125 (from prior study)	Vaginal progesterone	18.7% miscarriages
Eggimann [18]	Retrospective/threatened miscariage (including pts with habitual miscarriage or uterine malformations without bleeding)	238 pts with hexoestrol + DYD; 61 pts with buphenine +DYD	Bed rest, 17β-hydroxy-progesterone caproate, DYD,and hexoestrol/ buphenine	Miscarriage rate 21%, with hexoestrol, 16%, with buphenine.	Cheilognathourano-schisis, cheilognatho-schisis, hypospadias, duodenal atresia, hip dislocation (3 infants), cryptor-chidism, naevus, pes planus, pes valgus
				214 full-term babies;
				29 (11%) premature births (p < 0.0005)
		243 normal pregnant women	No treatment	No miscarriages	Fallot’s tetralogy, hypoplastic left heart, trisomy 21, bilateral cheilognathourano-schisis, hypoplasia of the right humerus, radius and ulna and 3 fingers on right hand, hypospadias (2 cases), hooked foot.
		243 normal pregnant women	No treatment	228 full-term babies; 15 (5%) premature births
Yamamoto [23]	Open-label/threatened miscarriage	24 pts	DYD	8 normal deliveries, 7 good (ongoing regnancy),	No side effects
		24 pts	DYD	9 miscarriages/D&C	No side effects
		26 pts	17β-hydroxy-progesterone caproate	18 deliveries, 1 ongoing pregnancy,	No side effects
		26 pts	17β-hydroxy-progesterone caproate	6 miscarriages, 1 pt not reported	No side effects
Uncontrolled studies
Chang [24]	Threatened miscarriage <20 weeks gestation	7 pts	DYD	1 term baby,	No abnormalities or side effects noted. No masculinizing effects.
				2 ongoing pregnancies 2 miscarriages, 2 premature – not viable
					2 pts with vomiting and nausea.
Gronow [25]	Threatened miscarriage	11 IVF pregnancies with bleeding	DYD	2 miscarriages	Safety and tolerability data not reported.
Ketkar [26]	Threatened miscarriage in first trimester	42 pts	DYD plus folic acid.	38 pregnancies continued, 25 deliveries,	All infants normal,
				38 pregnancies continued, 25 deliveries,	Apgar scores, 8–10
				13 ongoing pregnancies, 4 missed miscarriages	Apgar scores, 8–10
Case series
Aydar and Greenblatt [27]	Threatened miscarriage	7 pts	DYD	2 miscarriages, 3 term deliveries,	Well accepted. Virtually no undesirable side effects in 192 pts treated for different indications.
Aydar and Greenblatt [27]	Threatened miscarriage	7 pts	DYD	2 ongoing pregnancies without problems at time of report.
Backer [28]	Threatened miscarriage	36 pts	DYD	24 pregnancies continued (16 term deliveries, 2 premtures, 6 ongoing pregnancies at time of report; 12 miscarriages.	No genital abnormalities,
					no effect on hemato-poietic system, liver or kidney function.
					No side effects.
Gellé and Shaeffer [29]	Threatened miscarriage	20 pts	DYD	12 miscarriages	Severe nausea and vomiting in 1 pt who was withdrawn.
Gellé and Shaeffer [29]	Threatened miscarriage	20 pts	DYD	8 pregnancies continued (7 delivered at term, 1 in 8th month, all 8 infants normal	Severe nausea and vomiting in 1 pt who was withdrawn.
Jamain and Grenrt [30]	Threatened miscarriage	19 pts	DYD,	9 term pregnancies, 5 ongoing pregnancies,	“Perfectly well tolerated”
Jamain and Grenrt [30]	Threatened miscarriage	19 pts	DYD,	4 miscarriages, 1 with chromosomal aberration.	“Perfectly well tolerated”
Sureau and Combourieu [31]	Threatened miscarriage	23 pts	DYD	10 term deliveries, 10 ongoing pregnancies, 3 miscarriages.	Well tolerated, all infants healthy

Aes, adverse events; b.i.d., twice daily; CI, confidence interval; CNS, central nervous system; CON, control; D&C, dilation and curettage; DYD, dydrogesterone; i.m., intramuscular; PROG, progesterone; pt(s), patient(s); t.i.d., three times daily; yrs, years.