Metformin and Pregnancy Outcomes: Evidence Gaps and Unanswered Questions.

Background: Metformin is sometimes used as an alternative to insulin in gestational diabetes mellitus (GDM). It is also used to achieve ovulation in polycystic ovary syndrome (PCOS). Pre-natal exposure to metformin results from its continuation after a successful ovulation in women with PCOS, its maintenance in women with pre-gestational diabetes or the installation of metformin in GDM. Little is known about the potential consequences of metformin exposure on pregnancy outcomes and offspring development. The aim of this review is to summarize the metformin effects on pregnancy outcomes and offspring development. Gaps in the available evidence and unanswered questions are also discussed.

Methods: A comprehensive literature search was carried out to identify eligible studies from MEDLINE/PubMed, EMBASE and SCIELO databases through 1995 first semester.

Results: Several factors limit the effect of metformin on embryos. In contrast, placental transport of metformin is effective allowing for a higher fetal exposure; the impact of this finding remains unclear. It seems that the interruption of metformin after a pregnancy diagnosis in women with PCOS is not associated with a higher miscarriage risk and it continuation does not seem to impair the maternal metabolic prognosis or prevent emerging GDM.

Conclusions: It seems to have no sense to prolong the use of metformin after a pregnancy diagnosis in women with PCOS. Patients with GDM may be treated with metformin under on judicious basis, and a careful attachment to clinical guidelines and regulations is recommended. The long-term effects of pre-natal exposure to metformin on the offspring remain uncertain.