Targeted immunotherapy of high-grade cervical intra-epithelial neoplasia: Expectations from clinical trials.

Targeted immunotherapy of high-grade cervical intra-epithelial neoplasia (CIN) has been developed as an alternative to conization, to preserve future reproductive outcomes and avoid human papillomavirus (HPV) persistence. The objectives of the review are to present drugs according to their process of development and to examine their potential future use. A search for key words associated with CIN and targeted immunotherapy was carried out in the Cochrane library, Pubmed, Embase, and ClinicalTrials.gov from 1990 to 2016. Publications (randomized, prospective and retrospective studies) in any language were eligible for inclusion, as well as ongoing trials registered on the ClinicalTrials.gov website. Targeted immunotherapy includes peptide/protein-based vaccines, nucleic acid-based vaccines (DNA), and live vector-based vaccines (bacterial or viral). A total of 18 vaccines were identified for treatment of CIN at various stages of development, and the majority were well-tolerated. Adverse effects were primarily injection site reactions and flu-like symptoms under grade 2. The efficacy of vaccines defined by regression of CIN2/3 to no CIN or CIN1 ranged from 17 to 59% following a minimum of a 12-week follow-up. In the majority of studies, there was no association demonstrated between histological response and HPV clearance, or between histological or virological response and immune T cell response. Given that the spontaneous regression of CIN2/3 is 20-25% at 6 months, targeted immunotherapy occurs an additional value, which never reaches 50%, with one trial an exception to this. However, research and development on HPV eradication drugs needs to be encouraged, due to HPV-associated disease burden.

Outcome of patients with uterine fibroids after 3-month ulipristal acetate therapy.

OBJECTIVES: To determine the proportion and the characteristics of patients who did or did not respond after 3 months of ulipristal acetate (UPA) therapy. STUDY DESIGN: In this retrospective cohort study conducted in the University Hospital of Bordeaux (France) and University Medical Center Ljubljana (Slovenia), symptomatic non-menopausal patients with fibroids that qualified for surgery were pretreated by 3 months of oral UPA 5 mg/day. Clinical success was defined by normalization of the bleeding score, and/or regression of pelvic pain, and/or abdominal distension. Imaging success was defined by reduction in fibroid volume ≥ 25%. RESULTS: The clinical and imaging success rates were 54/66 (82%) and 39/66 (59%) respectively. The absence of previous pregnancy (p = 0.004) and the size of the dominant fibroid ≥ 80 mm (p = 0.004) were independent factors associated with clinical failure. Age <35 years (p = 0.02) was the only independent factor associated with imaging failure. CONCLUSION: Young women developing fibroids and/or women with large fibroids may be resistant to ulipristal acetate therapy.

Myomectomy: technique and current indications.

Uterine fibroids are the commonest benign tumor of the female genital tract. They affect a significant proportion of reproductive aged women and may cause excessive menstrual bleeding, pelvic pain or pressure, and adversely affect reproductive outcomes. However, many women remain asymptomatic. Fibroids are the first indication for hysterectomy, but myomectomy is the most suitable surgical option for women who desire preservation of their fertility potential. Only a selected group of women of childbearing age will benefit from a myomectomy, as the consequences of myomectomy on reproductive function have remained controversial. The purpose of this paper was to review the main surgical approaches for myomectomy, and discuss evidence-based indications for myomectomy in women with fibroids, especially with regards to its impact on fertility and reproductive outcomes. A critical review of the literature pertaining to the surgical approaches of myomectomy and the indications for myomectomy was performed, focusing on their impact on fertility and reproductive outcomes. Myomectomy is useful for the treatment of symptomatic fibroids and in selected women with infertility. Symptomatic submucosal fibroids are classically treated by hysteroscopic resection. Symptomatic intramural and subserosal fibroids may be treated by myomectomy, either by laparotomy or laparoscopy depending on their number and size. Prophylactic myomectomy is not recommended for preventing obstetrical complications or the risk of leiomyosarcoma. Although fibroids may have a negative effect on fertility, only the removal of submucosal fibroids has been consistently shown to improve spontaneous fertility or outcomes of assisted reproduction technology.