**5.1. Pessaries vs. capsules**

160 Enhancing Success of Assisted Reproduction

hepatic and hepatic metabolism [23].

women.

**4.4. Oral micronized progesterone vs. I.M progesterone** 

**4.5. Vaginal vs. IM progesterone for luteal support** 

Oral micronized progesterone for luteal phase support in ART not only results in significantly lower rates of pregnancy and implantation compared with those for I.M. , hCG or progesterone, but also causes more side effects [36] .In a prospective randomized study, the implantation rate was significantly lower in the oral micronized progesterone arm compared with I.M. progesterone. There was no significant difference in pregnancy rate between both groups [37] As mentioned above parenteral administration of progesterone, vaginally or I.M, does not subject the compound to the significant metabolic consequences of oral administration. Progesterone administered orally is subjected to first-pass pre-

Previous randomized trials [38 ,39] and a meta-analysis [18] and a Cochrane review [19] concluded that there is evidence of superiority of I.M. over vaginal progesterone for ongoing pregnancy and live birth. These studies showed that whether natural or synthetic I.M progesterone were used the results were the same : superiority of I.M. over vaginal ` progesterone For example at least two prospective randomized trials [40,41] showed that biweekly I.M. 250 mg 17-alpha hydroxyl progesterone caproate (17 –αHPC) was superior to daily 90 mg vaginal gel. However more recent randomized trials [42 ,43] and Cochrane systematic reviews found no evidence favoring vaginal vs. I.M. administration of progesterone. The last Cochrain review and meta-analysis [21] is particularly relevant because it is the most recent (2011) and it included Sixty-nine studies with a total of 16,327

**5. Comparison of different vaginal progesterone preparations** 

Natural progesterone have been incorporated in different forms for vaginal adminstration.e.g. vaginal tablets or capsules , vaginal pessaries and vaginal gel. The tablets adsorb the vaginal secretions and disintegrate into an adhesive powder that adheres to the vaginal epithelium, thus facilitating sustained absorption and reduced perineal irritation [44]. Each vaginal insert delivers 100 mg of progesterone in a base containing excipients conventionally used for solid oral dosage forms: lactose monohydrate, polyvinylpyrrolidone, adipic acid, sodium bicarbonate, sodium lauryl sulfate, magnesium stearate, pregelatinized starch, and colloidal silicone dioxide. Vaginal suppositories (e.g. Cyclogest)., contain semi-synthetic glycerides produced from interesterification of hydrogenated vegetable oil. The carrier vehicle in gel preparations (e.g. Crinone) is an oil-in-water emulsion containing polycarbophil, a bioadhesive and water-swellable polymer [28]. The water phase bypasses dependence on the local vaginal moisture, which is highly variable. The progesterone is sparingly soluble in oil (1:30 w/w) and practically insoluble in water (1:10,000 w/w) therefore the majority of the progesterone exists in a suspended form. The emulsion containing both dissolved and suspended progesterone adheres to the vaginal epithelial cells and thereafter-dissolved A prospective randomized study [45] compared the luteal serum hormone level, effectiveness and tolerability of two different vaginal formulations of micronized progesterone, vaginal pessaries (Ellios) and capsules (Uterogestan) , used for luteal phase support after an in vitro fertilization (IVF). Patients received Ellios pessaries (2 times 200-mg pessary/day) or Utrogestan capsules (2 100-mg capsules, two times a day). Progesterone was administered from the day of oocyte pickup (day 0) until menses or up to 10 weeks in pregnant patients. The outcome measures showed that progesterone levels on days 0, 9, 16 were not statistically different between the two formulations. The pregnancy rate were similar in the two groups (25.5% vs. 18.6%), whereas tolerance was signicantly better in pessaries` group versus capsules` group (vaginal discharge: 43% vs. 82%).
