Comparison of daily vaginal progesterone gel plus weekly intramuscular progesterone with daily intramuscular progesterone for luteal phase support in single, autologous euploid frozen-thawed embryo transfers

Abstract

Purpose To compare outcomes between daily intramuscular progesterone (IMP) and daily vaginal progesterone (VP) gel plus weekly intramuscular hydroxyprogesterone caproate (IMHPC) for luteal phase support (LPS) in single, autologous euploid frozen-thawed blastocyst transfers (FBTs) following artificial endometrial preparation (EP). Methods The retrospective cohort study included 767 single, autologous FBTs from 731 patients between January 2015 and March 2018. LPS was performed either with IMP (100 mg/day) or with VP gel (90 mg, twice daily) plus IMHPC (250 mg/week). Oral estrogen was prescribed in combination of both regimes. Oral estrogen was discontinued following the visualization of fetal cardiac activity on ultrasound and progesterone at 10 weeks of gestation. The primary outcome was live birth rate. The secondary outcomes included implantation, clinical pregnancy, and multiple pregnancy rates. Results Patient characteristics did not differ in LPS regimes. Of 767 FBTs, 608 had IMP (100 mg/day) for LPS and 159 had VP gel (90 mg, twice daily) plus IMHPC (250 mg/week) for LPS. The live birth rate was 51.8% and 50.3%, respectively (p = 0.737, OR 0.94, 95%CI 0.66-1.33). The implantation rate was 62.7% and 64.2%, respectively (p = 0.730, OR 1.06, 95%CI 0.74-1.53). The clinical pregnancy rates were also similar in both groups (59.5% vs. 61.6%, respectively, p = 0.631, OR 1.09, 95%CI 0.76-1.56). Conclusions We did not observe significant differences in the rates of live birth, implantation, and clinical pregnancy between daily IMP and daily VP gel plus weekly IMHPC for LPS in single, autologous euploid FBTs after artificial EP.

Serum luteal phase progesterone in women undergoing frozen embryo transfer in assisted conception: a systematic review and meta-analysis

“…This may additionally reflect the phenomenon of first uterine pass, whereby a targeted delivery of vaginal progesterone to the uterus enhances the local endocrine milieu and hence facilitates implantation and pregnancy success (60). Overall, however, studies comparing different routes and regimens of LPS in FET have failed to categorically identify a formulation with superior results (42,47,(61)(62)(63)(64)(65).…”

“…There were originally concerns with reduced bioavailability of natural progesterone due to its large molecular size, but in its micronized form progesterone has since been shown to be easily absorbed by the vaginal and intestinal mucosa (66,67). Furthermore, gel-based formulations containing micronized progesterone exhibit a sustained-release mechanism which leads to steady levels of absorption over time and prevents excessive variation in serum progesterone levels (63,64). The vaginal formulation is most commonly used in ART treatment across the world, and the preferred route of administration for up to one in four ART practitioners (68).…”

Adding Weekly Intramuscular Progesterone to a Twice Daily Vaginal Progesterone Capsule for Luteal Phase Support in IVF/ICSI Cycles Results in Similar Live Birth Rates

“…However, we did not detect any difference between agonist and antagonist groups with respect to BPR and LBR. Two other studies analyzed VP in comparison to IMP for luteal phase support and found that VP resulted in better clinical pregnancy outcomes that could be due to progesterone's local effect inducing secretory transformation of the endometrial stroma (Ho et al ., 2008; Satir et al ., 2013 ; Asoglu et al ., 2019 ). This study is limited due to its retrospective design.…”

Pharmacokinetics, safety and bioequivalence of two formulations of progesterone soft capsule in healthy Chinese postmenopausal females: Impacts of a high‐fat meal

“…By far, the pharmaceutical industry has developed several different dosage forms of progesterone available for intramuscular injection, oral and vaginal administration 7–10 . When encapsulated in the soft capsule, micronized progesterone can be absorbed through the gastrointestinal tract or vaginal mucosa.…”

“…6 By far, the pharmaceutical industry has developed several different dosage forms of progesterone available for intramuscular injection, oral and vaginal administration. [7][8][9][10] When encapsulated in the soft capsule, micronized progesterone can be absorbed through the gastrointestinal tract or vaginal mucosa. Progesterone exhibits linear and dose-dependent pharmacokinetics under multiple doses ranging from 100 to 300 mg/day in postmenopausal women.…”