Volume 27, Issue 2 - Special issue: Hormones in Normal and Pathological Pregnancies - Continued / Editors: Adolf E. Schindler and Jorge R. Pasqualini

Over time, it became evident that with the use of micronized progesterone and dydrogesterone prevention or treatment of pregnancy disorders such as threatened miscarriage, recurrent (habitual) miscarriage, preterm labor or preeclampsia appears to be possible. The results so far obtained will be delineated and concepts of prevention or treatment are suggested with the aim to further explore these pregnancy disorders either by prevention or treatment concepts to obtain not only benefits to the mother and the fetus, but furthermore this results in benefits for lifetime for the individual, for the family and last but not least for society.

Progestational agents are often prescribed to prevent threatened miscarriage progressing to miscarriage, and subsequent miscarriages in recurrent pregnancy loss. Progestogens affect implantation, cytokine balance, natural killer cell activity, arachidonic acid release and myometrial contractility. A recent Cochrane review reported that progestogens were effective for treating threatened miscarriage with no harmful effects on mother or fetus. The results were not statistically different when vaginal progesterone was compared to placebo, (RR=0.47, 95% CI 0.17–1.30), whereas oral progestogen (dydrogesterone) was effective (RR=0.54, CI 0.35–0.84). The review concluded, that the small number of eligible studies, and the small number of the participants, limited the power of the metaanalysis. A later metaanalysis of five randomised controlled trials of threatened miscarriage comprised 660 patients. The results of 335 women who received dydrogesterone were compared to 325 women receiveing either placebo or bed rest. There was a 47% reduction in the odds ratio for miscarriage, (OR=0.47, CI 0.31–0.7). There was a 13% (44/335) miscarriage rate after dydrogesterone administration compared to 24% in control women. Recurrent miscarriage affects approximately 1% of women of child bearing age. A metaanalysis of progestational agents shows a 26% increase in the live birth rate. Again, dydrogesterone was associated with a more significant increase in the live birth rate than the other progestogens included in the metaanalysis.

Progesterone is indispensable for the maintenance of pregnancy, both via its endocrine effects and its role in creating a favorable immunological environment for the fetus. This review focuses on the immunological effects of progesterone. Progestogens have been shown to have very interesting effects on cytokine production and decidual natural killer (NK) cell activity. The orally-administered progestogen, dydrogesterone, has the ability to modulate cytokine production patterns in a manner that could be conducive to successful pregnancy. The adverse effects of progesterone deficiency and the beneficial effects of progesterone supplementation in pregnancy pathologies will be discussed.

Introduction: Gestational hypertension remains one of the main causes of maternal deaths all over the world. Attempts to reduce/prevent the incidence had failed due to lack of understanding of the disease’s aetiology. One of the early roles of natural progesterone in the first trimester of pregnancy is to promote formation of wide-calibre spiral vessels that invade into the myometrial layer of the gravid uterus. Theoretically, this will prevent or reduce the incidence of gestational hypertension in the latter half of the pregnancy. Review: The progestogen, dydrogesterone, has similar molecular structure and properties to natural progesterone. A pilot study was undertaken on primigravidae, who have higher risk of developing gestational hypertension. They were supplemented with dydrogesterone in the first trimester (Study Group) and compared with a similar number of primigravidae (Control Group) without supplementation with the progestogen. The incidence of gestational hypertension was significantly lower in the Study Group as compared to the Control Group (1.7% vs. 12.9%, respectively, p<0.001). The incidence of foetal distress was also significantly lower in the Study Group compared to the Control Group (4.3% vs. 18.1%, respectively, p<0.001). Conclusion: Supplementation of the progestogen, dydrogesterone, in the first trimester to primigravidae has shown great potential in reducing or preventing the incidence of gestational hypertension.

Adenomyosis is a common gynaecological disorder that is associated with infertility and miscarriage. We report a case of adenomyosis presented with urinary retention and infertility. The patient successfully conceived spontaneously following GnRHa followed by progestogen therapy. This treatment option might provide a synergistic effect in improving fertility and pregnancy outcome for women with adenomyosis. This modality has no potential surgical risk; it minimises the long-term side effects of GnRHa and also provides luteal support.