Luteal support: progestogens for pregnancy protection

Abstract

Following ovulation, the granulosa cells undergo luteinization and form part of the corpus luteum; this then secretes progesterone that causes secretory transformation of the endometrium so that implantation can occur. The ideal time for implantation is 6-10 days after the luteinizing hormone (LH) surge; implantation occurring outside this optimal window is associated with a higher likelihood of miscarriage. Before the placenta takes over progesterone production, the progesterone produced by the corpus luteum also provides the necessary support to early pregnancy. A defect in corpus luteum function is not only associated with implantation failure but also with miscarriage. In assisted reproduction, both the use of gonadotropin-releasing hormone analogues to prevent the LH surge and aspiration of granulosa cells during the oocyte retrieval may impair the ability of the corpus luteum to produce sufficient progesterone. This may be treated effectively with progestational agents such as progesterone or dydrogesterone, which have a very similar pharmacological profile. Studies indicate that an estrogen may be given during the luteal phase to optimise the estrogen:progestogen ratio to facilitate implantation, although the available evidence is inconsistent in its strength for this hypothesis. In addition to assisted reproduction, progestational agents have shown beneficial effects in the management of patients with recurrent spontaneous miscarriage of unknown cause. In conclusion, despite the wide-spread use and many years of clinical experience, the amount of data from well-controlled clinical trials is currently limited. Further studies are therefore required to establish the optimal treatment situation and type and dose of progestational agent.