1. Dydrogesterone : a Possible Preventative Treatment for Preterm Delivery.
Y Muscat Baron, M. Z. Mangion, M Formosa, R Galea, M Brincat. Department of Obstetrics and Gynaecology,
St Luke’s Hospital
Mater Dei Hospital,
Malta

2. Preterm Labour and Perinatal Morbidity
Preterm labour is the most common cause of fetal morbidity and perinatal mortality.
The incidence of preterm labour (under 34 weeks of gestation) in Malta and Gozo between the years 1999 and 2005 is 1.9%1
Perinatal Mortality Rate in Maltese Islands 1998 – % (<34weeks)

3. Risk Factors for Preterm Labour
Maternal history
Previous history of preterm delivery
Previous history of a second-trimester abortion
Trauma
Threatened miscarriage
Uterine volume increased
Uterine factors
Uterine anomalies
Infection
Maternal factors
Low socioeconomic status
Nonwhite race
Maternal age <=18 or >=40 years
Low prepregnancy weight
Smoking
Substance abuse.

4. Meis et al 2004 De Fonseca et al 2003
Two recent double-blind, placebo-controlled trials indicated that progesterone may be useful in preventing preterm delivery in high risk patients.

5. Rationale of Study
A possible alternative to the above progesterone treatments is dydrogestrone which is a progestin in oral form.
Dydrogesterone is used in cases of miscarriage with significant success. (Szekeres J et al,)
The rationale of this study is that preterm labour is a continuum of pregnancy loss similar to miscarriage differing in that it occurs at a later stage.
Progesterone has also been implicated in reducing the incidence of pre-eclampsia a common cause of preterm delivery (Schindler et al Steroids 2002).

6. p < 0.01

7. p < 0.05

8. p = 0.25 NS

9. Dydrogesterone for the prevention of Preterm Delivery
RESULTS Control Group Duphaston Grp
< 37 weeks /140 (7.1%) 6/76 (7.9%) p = N.S.
< 34 weeks /140 (2.8%) 2/76 (2.6%) p = N.S.
Maltese Preterm Delivery Statistics
<37 weeks % <34 weeks – 1.9% ``

10. P-receptors in Pregnancy Lymphocytes
PIBF
V1
CD56+
Trophoblast
Th1
Th2
V1
CD56+
PR+
Activation P +
The immunological effects of progesterone are mediated via a 34kDa protein called Progesterone Induced Blocking Factor (PIBF). Szekeres-Barthó J. Int Immunopharm 2001; 1:1037.

11. Effect of Dydrogesterone on PIBF Induction60 50 40 30
PIBF positive cells (%) 20 10
1.5 3 6 12 25 50
100
Dydrogesterone concentration µg/ml
Szekeres-Barthó J. Gynecological Endocrinology 2001; 15 (S5): 43.

12. Conclusion Preterm labour is costly in both human and financial terms.
Progesterone in different forms appears to reduce the preterm delivery rate.
This may be due to immunomodulation during pregnancy mediated via PIBF.
Dydrogesterone in high risk pregnancies showed comparable preterm delivery rates 7.9% vs 7.1% as the control population.
Dydrogesterone did not reveal any teratogenic effects.
In high risk pregnancies dydrogesterone may be a useful adjunct to prevent preterm delivery

13. “You are carved in the palm of my hand
“You are carved in the palm of my hand. You will never be forgotten” Isaiah 49:15
SANDS MEMORIAL
MALTA