Premature ovarian insufficiency (POI) occurs in 1% of reproductive-age women. The ovarian manifestation ranges from the presence of a variable population of follicles (follicular) to the absence of follicles (afollicular), and in the majority of cases the cause is unknown. A transgenic mouse model of follicular POI, the Double Mutant (DM), arises from oocyte-specific deletion of Mgat1 and C1galt1 required for the generation of O- and N-glycans. DM females are subfertile at 6 weeks, infertile by 9 weeks and exhibit POI by 12 weeks of age. In this study we investigate the cause of the reduced fertility at 6 weeks and infertility at 9 weeks of DM females. Ovary sections were used to analyse follicle and corpora lutea (CL) numbers, apoptosis, and levels of laminin and 3β-hydroxysteroid dehydrogenase using immunohistochemistry. After POI, DM females unexpectedly remained sexually receptive. At both 6 and 9 weeks, DM ovaries contained more primary follicles, however, at 9 weeks DM follicles were proportionally healthier, revealed by TUNEL analysis compared with Controls. In 9 week DM ovaries (collected post-mating), secondary follicles had theca and basal lamina structure abnormalities, whilst preovulatory follicles failed to ovulate resulting in the presence of numerous luteinised unruptured follicles, indicative of ovulation failure. Finally, DM ovaries contained more regressing CL with decreased luteal cell apoptosis indicative of a defect in CL regression. Identifying these follicular modifications have provided insight into the aetiology of a model of POI and highlight targets to investigate with the hope of developing new fertility treatments.

BackgroundEctopic pregnancies are a leading cause of maternal mortality. Most are treated surgically. We evaluated the efficacy and safety of combining oral gefitinib (epidermal growth factor receptor inhibitor) with methotrexate to treat larger ectopic pregnancies.MethodsWe performed a phase II, single arm, open label study across four hospitals in Edinburgh and Melbourne. We recruited women with a stable tubal ectopic pregnancy and a pre-treatment serum hCG between 1000 and 10,000 IU/L. We administered intramuscular methotrexate (50 mg/m2) once, and oral gefitinib (250 mg) for seven days. The primary outcome was the percentage successfully treated without needing surgery. To show the treatment is at least 70% effective, 28 participants were required, and 24 or more successfully treated without surgery. Secondary outcomes were safety, tolerability, and time to resolution. This study is registered (ACTRN12611001056987).Findings30 participants with stable tubal ectopic pregnancies were recruited but two withdrew, leaving 28 participants. The median (± range) pre-treatment serum hCG was 2039 (1031–8575) IU/L and nine had pre-treatment hCGs levels >3000 IU/L. The treatment successfully resolved 86% (24/28) cases with a median (±range) time to resolution of 32 (18–67) days. The treatment caused transient rash and diarrhoea, but no serious adverse events.InterpretationCombination gefitinib and methotrexate is at least 70% effective in resolving ectopic pregnancies with a pre-treatment serum hCG 1000–10,000 IU/L. This may be a new way to treat most stable ectopic pregnancies, but needs to be validated via a randomised clinical trial.

The maxillofacial region is an uncommon site for metastases from distant primary tumours, representing only 1–2% of malignancies at this site. Such metastases usually present in the mandible rather than the maxilla. The most common sites of primary tumour are the breast, lung and kidney. We describe the clinical, radiological and histologic features of the first‐known case of a low‐grade serous carcinoma of the ovary metastasising to the posterior maxilla. Low‐grade serous carcinoma of the ovary is an uncommon entity and is biologically distinct from high‐grade serous carcinoma. Extra‐abdominal spread is uncommon and bony metastases are rare. Intraosseous metastases are often associated with disseminated disease and confer a poor prognosis.

therapy and MCT diet). Octreotide therapy and MCT diet were started 3 days after surgery. Clinical courses between group A (n=17) and B (n=10) were compared. Results There were no differences in clinicopathologic characteristics including dissected para-aortic lymph node counts between the two groups. The median duration of pelvic drain (14.0 days, 8.0 -21.0 days vs. 7.0 days, 6.0 -8.0 days, p < 0.001) and hospital stay (15.0 days, 10.0 -22.0 days vs. 10.0 days, 8.0 -13.0 days, p = 0.002) were significantly different between the two groups. There was no recurrence of lymphatic ascites after early octreotide therapy and MCT diet. Conclusions Early octreotide therapy and MCT diet in gynecological cancer patient who underwent para-aortic lymphadenectomy up to the level of renal vein may be attempted to shorten hospital stay and prevent lymphatic ascites. However, the timing of initiation of early octreotide therapy and MCT diet should be determined through further studies in more patients.