暂无摘要。

The recent advent of embryo vitrification and its remarkable efficacy has focused interest on the quality of hormone administration for priming frozen embryo transfers (FETs). Products available for progesterone administration have only been tested in fresh assisted reproduction technologies (ARTs) and not in FET. Recently, there have been numerous concordant reports pointing at the inefficacy of vaginal preparations at delivering sufficient progesterone levels in a sizable fraction of FET patients. The options available for coping with these shortcomings of vaginal progesterone include (i) rescue options with the addition of injectable subcutaneous (SC) progesterone at the dose of 25 mg/day administered either solely to women whose circulating progesterone is <10 ng/mL or to all in a combo option and (ii) the exclusive administration of SC progesterone at the dose of 25 mg BID. The wider use of segmented ART accompanied with FET forces hormone replacement regimens used for priming endometrial receptivity to be adjusted in order to optimize ART outcomes.

For decades, there has been a growing interest in injectable subcutaneous formulations to improve the absorption of drugs into the systemic circulation and to prolong their release over a longer period. However, fluctuations in the blood plasma levels together with bioavailability issues often limit their clinical success. This warrants a closer look at the performance of long-acting depots, for example, and their dependence on the complex interplay between the dosage form and the physiological microenvironment. For this, biopredictive performance testing is used for a thorough understanding of the biophysical processes affecting the absorption of compounds from the injection site in vivo and their simulation in vitro. In the present work, we discuss in vitro methodologies including methods and media developed for the subcutaneous route of administration on the background of the most relevant absorption mechanisms. Also, we highlight some important knowledge gaps and shortcomings of the existing methodologies to provide the reader with a better understanding of the scientific evidence underlying these models.

Methotrexate (MTX) is standard treatment for RA. Absorption is better in subcutaneous MTX (scMTX), which may impact speed of onset. In RA, earlier time to remission improves long-term results. Our objectives were to determine rapidity of response of subcutaneous methotrexate in early rheumatoid arthritis.
The change in several disease activity measures (including DAS28) from 0 to 6 weeks (early period) and 6 to 12 weeks (late period) was compared. The proportion achieving DAS28/CDAI/SDAI remission and/or low disease activity state was also compared.
One hundred three patients were included from a single site between 2008 and 2014. All received MTX (98.0 % scMTX, 98 % 25 mg/week). There were no dropouts. There was a significantly greater early change in DAS28 (-1.9 vs. -0.2, p < 0.00); this effect was seen for several outcome measures. By 6 weeks, 59 % had achieved either DAS28 remission or low disease activity state, with 74 % achieving either state by 12 weeks. There were a larger proportion of patients achieving CDAI and DAS28 remission in the early versus late period (p < 0.0002 for both). There was significant improvement when using combination MTX and HCQ, however sample size was small (n = 9). The use of intra-articular steroids with MTX yielded the most disease measures that demonstrated early significant improvement.
Subcutaneous MTX is rapid, as the change in many disease activity scores was significantly greater between 0-6 weeks compared to 6-12 weeks. Combination MTX + HCQ gave added value, although generalizability is limited by combination cohort sample size. Intra-articular steroid injections may contribute to the early effect.