A randomized, controlled trial comparing the efficacy and safety of aqueous subcutaneous progesterone with vaginal progesterone for luteal phase support of in vitro fertilization.

STUDY QUESTION: Is the ongoing pregnancy rate with a new aqueous formulation of subcutaneous progesterone (Prolutex(®)) non-inferior to vaginal progesterone (Endometrin(®)) when used for luteal phase support of in vitro fertilization? SUMMARY ANSWER: In the per-protocol (PP) population, the ongoing pregnancy rates per oocyte retrieval at 12 weeks of gestation were comparable between Prolutex and Endometrin (41.6 versus 44.4%), with a difference between groups of -2.8% (95% confidence interval (CI) -9.7, 4.2), consistent with the non-inferiority of subcutaneous progesterone for luteal phase support. WHAT IS KNOWN ALREADY: Luteal phase support has been clearly demonstrated to improve pregnancy rates in women undergoing in vitro fertilization (IVF). Because of the increased risk of ovarian hyperstimulation syndrome associated with the use of hCG, progesterone has become the treatment of choice for luteal phase support. STUDY DESIGN, SIZE, DURATION: This prospective, open-label, randomized, controlled, parallel-group, multicentre, two-arm, non-inferiority study was performed at eight fertility clinics. A total of 800 women, aged 18-42 years, with a BMI of ≤ 30 kg/m(2), with <3 prior completed assisted reproductive technology (ART) cycles, exhibiting baseline (Days 2-3) FSH of ≤ 15 IU/L and undergoing IVF at 8 centres (seven private, one academic) in the USA, were enrolled from January 2009 through June 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 800 women undergoing IVF were randomized after retrieval of at least three oocytes to an aqueous preparation of progesterone administered subcutaneously (25 mg daily) or vaginal progesterone (100 mg bid daily). Randomization was performed to enrol 100 patients at each site using a randomization list that was generated with Statistical Analysis Software (SAS(®)). If a viable pregnancy occurred, progesterone treatment was continued up to 12 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE: Using a PP analysis, which included all patients who received an embryo transfer (Prolutex = 392; Endometrin = 390), the ongoing pregnancy rate per retrieval for subcutaneous versus vaginal progesterone was 41.6 versus 44.4%, with a difference between groups of -2.8% (95% CI -9.7, 4.2), consistent with the non-inferiority of subcutaneous progesterone for luteal phase support. In addition, rates of initial positive ß-hCG (56.4% subcutaneous versus 59.0% vaginal; 95% CI -9.5, 4.3), clinical intrauterine pregnancy with fetal cardiac activity (42.6 versus 46.4%; 95% CI -10.8, 3.2), implantation defined as number of gestational sacs divided by number of embryos transferred (33.2 versus 35.1%; 95% CI -7.6, 4.0), live birth (41.1 versus 43.1%; 95% CI -8.9, 4.9) and take-home baby (41.1 versus 42.6%; 95% CI -8.4, 5.4) were comparable. Both formulations were well-tolerated, with no difference in serious adverse events. Analysis with the intention-to-treat population also demonstrated no difference for any outcomes between the treatment groups. LIMITATIONS, REASONS FOR CAUTION: The conclusions are limited to the progesterone dosing regimen studied and duration of treatment for the patient population examined in this study. WIDER IMPLICATIONS OF THE FINDINGS: Subcutaneous progesterone represents a novel option for luteal phase support in women undergoing IVF who for personal reasons prefer not to use a vaginal preparation or who wish to avoid the side effects of vaginal or i.m. routes of administration. STUDY FUNDING/COMPETING INTERESTS: The study was funded by Institut Biochimique SA (IBSA). CAJ, BC, ST and CJ are employees of IBSA. FH currently consults for IBSA. TRIAL REGISTRATION NUMBER: NCT00828191.

S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial. [ISRCTN36233495].

BACKGROUND: S-adenosylmethionine (SAMe) is a dietary supplement used in the management of osteoarthritis (OA) symptoms. Studies evaluating SAMe in the management of OA have been limited to Non Steroidal Anti-inflammatory Drugs (NSAIDs) for comparison. The present study compares the effectiveness of SAMe to a cyclooxygenase-2 (COX-2) inhibitor (celecoxib) for pain control, functional improvement and to decrease side effects in people with osteoarthritis of the knee. METHODS: A randomized double-blind cross-over study, comparing SAMe (1200 mg) with celecoxib (Celebrex 200 mg) for 16 weeks to reduce pain associated with OA of the knee. Sixty-one adults diagnosed with OA of the knee were enrolled and 56 completed the study. Subjects were tested for pain, functional health, mood status, isometric joint function tests, and side effects. RESULTS: On the first month of Phase 1, celecoxib showed significantly more reduction in pain than SAMe (p = 0.024). By the second month of Phase 1, there was no significant difference between both groups (p < 0.01). The duration of treatment and the interaction of duration with type of treatment were statistically significant (ps < or = 0.029). On most functional health measures both groups showed a notable improvement from baseline, however no significant difference between SAMe and celecoxib was observed. Isometric joint function tests appeared to be steadily improving over the entire study period regardless of treatment. CONCLUSION: SAMe has a slower onset of action but is as effective as celecoxib in the management of symptoms of knee osteoarthritis. Longer studies are needed to evaluate the long-term effectiveness of SAMe and the optimal dose to be used.