Systematic review of the clinical efficacy of vaginal progesterone for luteal phase support in assisted reproductive technology cycles

Abstract

Vaginal progesterone via capsule, gel or tablet is the most common route for luteal phase support (LPS) in Europe. Although there is a wealth of data comparing products used at other stages of assisted reproductive technology cycles, there is a lack of systematically identified evidence comparing the wide range of vaginal progesterone products. This systematic review queried the MEDLINE, Embase and Cochrane Library databases on 30 June 2016 to identify head-to-head randomized controlled trials (RCTs) comparing the efficacy or safety of vaginal progesterone preparations (Crinone, Cyclogest, Lutigest or Utrogestan Vaginal) for LPS in assisted reproductive technology cycles. Of 1914 results, 18 RCTs were included. No significant difference in clinical pregnancy rate was identified in comparisons of Utrogestan Vaginal with Crinone. Utrogestan Vaginal and Lutigest were non-inferior to Crinone in ongoing pregnancy rate comparisons. Differences in patient-reported perineal irritation with Crinone and Lutigest were not significantly different to Cyclogest. In studies comparing varying timing or dosage of Utrogestan Vaginal or Crinone, no significant differences were observed. These results suggest Crinone, Cyclogest, Lutigest and Utrogestan Vaginal represent equally safe and effective choices of vaginal progesterone for LPS in assisted reproductive technology cycles. Future quantitative analyses could provide further support for these findings.

<p>Pharmacokinetics of hard micronized progesterone capsules via vaginal or oral route compared with soft micronized capsules in healthy postmenopausal women: a randomized open-label clinical study</p>

“…Studies have claimed that due to the first-pass effect through the liver, oral progesterone was the least effective form, contrary to intramuscular, which was reported to be the most efficient 11. Many studies have confirmed that vaginal administration of micronized progesterone tablets and progesterone vaginal gel have similar effects on persistent pregnancy rate, but progesterone gel is more convenient to use 12–16. There have not been any studies undertaking comparative study of the PK parameters of Yimaxin.…”

Fetal nuchal translucency: is there an association with birthweight and neonatal wellbeing?

“…The present study established a positive association between first trimester NT and birthweight, although our study includes non-IVF patients. Some studies in literature demonstrated increased NT with the use of exogenous progesterone in the first trimester (21,22) , and it is widely known that progesterone is used in the luteal phase and the first trimester as a worldwide standard procedure in IVF patients (23,24) . Accordingly, the current study population was selected from non-IVF patients and those who did not use progesterone in the first trimester.…”

Evaluation of the Second Follicular Wave Phenomenon in Natural Cycle Assisted Reproduction: A Key Option for Poor Responders through Luteal Phase Oocyte Retrieval

“…A second follicular wave is indicated considering the high E2 levels recorded and evident through ultrasound evaluation [3]. However, due to high levels of progesterone—following the original ovulation and entering the luteal phase [58]—the SFW fails to lead to ovulation of the luteal phase Graafian follicle. It is evident that progesterone produced by the corpus luteum in luteal phase may contribute to the pituitary suppression through negative feedback, with the consequence of an anovulatory follicular wave [45].…”