Luteal Phase Support Using Subcutaneous Progesterone: A Systematic Review

Abstract

Luteal phase support (LPS) is crucial in assisted reproductive technology (ART) cycles when the luteal phase has been found to be defective. Such deficiency is most likely related to the supraphysiological steroid levels that usually occurr in stimulated cycles which, in turn, could severely affect luteinizing hormone (LH) secretion and function, thereby negatively influencing the luteal phase. A number of different medications and routes have been successfully used for LPS in ART. Although an optimal protocol has not yet been identified, the existing plethora of medications offer the opportunity to personalize LPS according to individual needs. Subcutaneous administration progesterone has been proposed for LPS and could represent an alternative to a vaginal and intramuscular route. The aim of the present systematic review is to summarize the evidence found in the literature concerning the application of subcutaneous progesterone in ARTs, highlighting the benefits and limits of this novel strategy. With this aim in mind, we carried out systematic research in the Medline, ISI Web of Knowledge, and Embase databases from their inception through to November 2020. Randomized controlled trials (RCTs) were preferred by the authors in the elaboration of this article, although case-control and cohort studies have also been considered. According to our findings, evidence exists which supports that, in women with a good prognosis undergoing a fresh in vitro fertilization (IVF) cycle, subcutaneous Pg is not inferior to vaginal products. In the Frozen-thawed embryo transfer (FET) cycle, data concerning efficacy is mixed with an increased miscarriage rate in women undergoing a subcutaneous route in oocyte donor recipients. Data concerning the acceptance of the subcutaneous route versus the vaginal route are encouraging despite the different scales and questionnaires which were used. In addition, a cost-effective analysis has not yet been conducted.

Corpus luteum and progesterones in embryo transfer cycles: current challenges of different luteal phase support protocols

“…When it comes to progesterone supplementation, natural progesterones present similar OPR, miscarriage rates (MR), and LBR outcomes through different routes of administration, whether vaginally or intramuscular ( Abdelhakim et al ., 2020 ). Also, there is some evidence regarding similar results using natural progesterone rectally ( Alsbjerg et al ., 2023 ) or subcutaneously ( Conforti et al ., 2021 ). The only oral progesterone with similar OPR, MR, and LBR and a good safety profile used for AC FET cycles is DYD ( Pabuccu et al ., 2022 ).…”

Comparative Bioavailability of Two Daily Subcutaneous Doses Versus a Single Dose of Intramuscular and Vaginal Progesterone Formulations in Healthy Postmenopausal Females

“…10 A recent systematic review found that there is reasonably good evidence that SC progesterone for luteal phase support in ART fresh cycles is noninferior to Vag administration in terms of pregnancy outcomes. 11 SC injections can be self-administered and may be associated with fewer injection site reactions than via the IM route. 11 IBSA Institut Biochimique SA has developed an SC progesterone preparation that is available in several countries for luteal support in patients undergoing infertility treatments.…”

“…11 SC injections can be self-administered and may be associated with fewer injection site reactions than via the IM route. 11 IBSA Institut Biochimique SA has developed an SC progesterone preparation that is available in several countries for luteal support in patients undergoing infertility treatments. The approved dose is 25 mg once daily from day of oocyte retrieval, usually until 12 weeks of confirmed pregnancy, based on studies conducted in fresh embryo transfer ARTs.…”

“…Progesterone administered via the SC route is rapidly absorbed and may reach peak serum levels more quickly than via the IM route 10 . A recent systematic review found that there is reasonably good evidence that SC progesterone for luteal phase support in ART fresh cycles is noninferior to Vag administration in terms of pregnancy outcomes 11 . SC injections can be self‐administered and may be associated with fewer injection site reactions than via the IM route 11 …”