Background: In an attempt to correct for the iatrogenic luteal phase defect induced by IVF, a multitude of studies have been conducted to assess the use of progesterone for luteal supplementation. The preponderance of these studies has shown a significant improvement in implantation and pregnancy rates with luteal progesterone supplementation compared to no supplementation (Pritts and Atwood, 2002). The addition of estradiol (E2) for luteal supplementation is more controversial. Studies investigating the addition of E2 (oral or transdermal) to standard progesterone luteal supplementation have been limited, and the results have been conflicting. Several randomized controlled studies have shown significantly higher implantation and pregnancy rates with addition of oral E2 in the luteal phase vs. placebo (Farhi et al., 2000; Lukaszuk et al., 2005) and that increasing the dose of E2 may further improve the outcomes (Lukaszuk et al., 2005). Recently, a large retrospective study by Leondires et al. (2006) showed that E2 supplementation (vs. no supplementation), regardless of ovarian stimulation protocol, increased pregnancy rates. However, a recent prospective study using transdermal E2 showed no benefit vs. placebo (Serna et al., 2006). The inconsistency between the studies showing improved outcome vs. no improvement with luteal phase E2 supplementation appears to be the route of administration (oral vs. transdermal). Objective: To compare the implantation and pregnancy rates of patients who received a combined regimen of oral and transdermal E2 compared with transdermal only E2 regimen. Materials and Methods: A retrospective chart review was performed. Women (40 years or younger with a minimum of 6 oocytes aspirated) who underwent IVF cycles with luteal oral and transdermal estradiol supplementation were identified during the period of August 2006 – November 2006 (Group 1). Group 1 received intramuscular P in oil, 2-mg E2 tablets orally three times a day, and two 0.1-mg transdermal E2 patches every 48 hours until negative pregnancy test or 10 week gestational age (n = 18). Age-matched women undergoing IVF during the same time period were chosen for controls (Group 2). Group 2 received intramuscular P in oil and two 0.1-mg transdermal E2 (n = 19). Patient characteristics, including, age, parity, number of failed ovulation induction cycles, characteristics of the IVF cycle including number of oocytes retrieved and fertilized, number of embryos implanted, and ongoing pregnancy, were recorded. Results: The demographic data between the two groups were similar. The results expressed as mean ± SD or percentages, as appropriate, are summarized below. Group 1 had significantly higher implantation and multiple pregnancy rates. However, the ongoing pregnancy rate was similar between the two groups.Tabled 1Group 1Transdermal/oral E2/PGroup 2Transdermal E2/PNumber of patients1819Age (years)33.2 ± 4.834.2 ± 4.3Peak E2 (pg/mL)3113.6 ± 1607.42364.6 ± 829.5Number of embryos transferred2.7 ± 1.002.7 ± 0.9Implantation rate∗42 (21/50)23 (12/52)Pregnancy rate55 (10/18)47 (9/19)Multiple pregnancy rate∗38 (7/18)10 (2/19) Open table in a new tab ∗ denotes significant P value (<.05). Conclusions: This preliminary data suggests that for luteal phase E2 supplementation combined regimen of luteal phase transdermal and oral E2 improves implantation rates compared to a transdermal E2 regimen. Although the pregnancy rate between the two groups is comparable, the women treated with the combined regimen of transdermal/oral E2 have a higher rate of implantation and multiple gestation.
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