The main sequelae of endometriosis are represented by infertility and chronic pelvic pain. Chronic pelvic pain causes disability and distress with a very high economic impact. In the last decades, an impressive amount of pharmacological agents have been tested for the treatment of endometriosis-associated pelvic pain. However, only a few of these have been introduced into clinical practice. Following the results of the controlled studies available, to date, the first-line treatment for endometriosis associated pain is still represented by oral contraceptives used continuously. Progestins represent an acceptable alternative. In women with rectovaginal lesions or colorectal endometriosis, norethisterone acetate at low dosage should be preferred. GnRH analogues may be used as second-line treatment, but significant side effects should be taken into account. Nonsteroidal anti-inflammatory drugs are widely used, but there is inconclusive evidence for their efficacy in relieving endometriosis-associated pelvic pain. Other agents such as GnRH antagonist, aromatase inhibitors, immunomodulators, selective progesterone receptor modulators, and histone deacetylase inhibitors seem to be very promising, but there is not enough evidence to support their introduction into routine clinical practice. Some other agents, such as peroxisome proliferator activated receptors-γligands, antiangiogenic agents, and melatonin have been proven to be efficacious in animal studies, but they have not yet been tested in clinical studies.

Interstitial pregnancy is defined as the presence of a gestational sac in the most proximal section of the fallopian tube. Management of interstitial pregnancy remains a debated topic. Depending on hemodynamic stability, size of pregnancy, depth of surrounding myometrium, and desires for future fertility, interstitial pregnancy can be managed medically or surgically. We reviewed the literature in December 2020 using keywords “interstitial pregnancy”, “medical treatment”, “methotrexate”, and “mifepristone”. Articles published from January 1991 until 2020 were obtained from databases EMBASE, SCOPUS, and PUBMED. We describe the case of a patient with an interstitial pregnancy that was managed with a total medical approach in August 2020 at Burlo Garofolo Hospital. The patient was asymptomatic and hemodynamically stable, with a high level of serum β-hCG (22,272 mUi/mL). We used the combination of methotrexate (MTX) and mifepristone. Medical therapy was effective leading to interstitial pregnancy resolution in 51 days without collateral effects for the patient. We found seven previous cases reported in the literature. Our purpose is to underline the efficacy of medical therapy with systemic multidose MTX associated with a single oral dose of mifepristone and also folinic acid when is present a viable fetus and a high serum β-hCG level.

Bromelain is a complex mixture of thiol proteases and other non-proteolytic constituents, commercially extracted primarily from the pineapple stem. Evidence from several in vitro and in vivo studies highlights its excellent bioavailability, lack of side effects, and broad spectrum of medical efficacies, of which the antiphlogistic properties are among the most valuable ones. Bromelain has indeed been employed for the efficient treatment of many inflammatory disorders, ranging from osteoarthritis and inflammatory bowel diseases to cancer-related inflammation. The aim of the current study was to assess the anti-inflammatory effects of bromelain after gastrointestinal digestion simulated in vitro using stomach, intestinal, and chondrocyte human cellular models (AGS, Caco-2, and SW1353, respectively). We successfully demonstrated the capability of bromelain to reduce an inflammatory stimulus by reproducing its exposure to the gastro-enteric environment in vitro and assaying its effect in human cell lines derived from stomach, intestinal, and chondrocytes. Consistently with the previously published data, our work underpins the relevance of bromelain in the development of safer and more effective anti-inflammatory therapies.