Hydatidiform molar pregnancy following assisted reproduction.

INTRODUCTION: The use of assisted reproduction techniques (ART) is increasing; however, reports of molar pregnancy following ART remain scarce. Currently, the Human Fertility and Embryology Authority (HFEA) collates data on the molar pregnancies that have resulted through the use of ART. Recently, they have indicated that they will no longer collect these data. AIM: This paper aimed to examine the incidence of molar pregnancy amongst patients undergoing assisted reproduction. METHODS: We contacted HFEA and placed a request under the Freedom of Information Act (2000) for the number of molar pregnancies that resulted from fresh/frozen embryo transfer since HFEA started collecting data in 1991 to February 2018. We also asked how many patients who had suffered a molar pregnancy went on to have a normal pregnancy and how many had subsequent molar pregnancies, in subsequent treatment cycles. RESULTS: Between 68 and 76 molar pregnancies occurred within this period using ART (n = 274,655). The incidence of molar pregnancy using fresh intracytoplasmic sperm injection (ICSI) (1/4302) and fresh in vitro fertilisation (IVF) (1/4333) was similar. The risk of recurrence of molar pregnancy following a previous molar was higher following ART compared to spontaneous conceptions. CONCLUSION: The use of ICSI should be protective against triploidy; however, the retrospective data suggests that molar pregnancy is not eliminated with the use of ART. It is pertinent to continue to record this data, through the gestational trophoblastic disease centres, in order to ensure no further increase in incidence, appropriate follow-up, and transparency in communication.

The effect of surgical management of endometrioma on the IVF/ICSI outcomes when compared with no treatment? A systematic review and meta-analysis.

OBJECTIVE: To assess the impact of surgical management of endometrioma on the outcome of assisted reproduction treatment (ART). DESIGN: A systematic review and meta-analysis. SETTING: Department of reproductive medicine at teaching university hospital, UK. PATIENTS: Subfertile women with endometrioma undergoing ART. INTERVENTIONS: Surgical removal of endometrioma or expectant management. MAIN OUTCOME MEASURES: Clinical pregnancy rate, pregnancy rate, live birth rate, number of oocytes retrieved and number of embryos available and ovarian response to gonadotrophins. RESULTS: An extensive search of electronic databases for articles published from inception to September 2016 yielded 11 eligible studies for meta-analysis. Meta-analysis was conducted comparing surgery versus no treatment of endometrioma. There were no significant differences in pregnancy rate per cycle, clinical pregnancy rate and live birth rate between women who underwent surgery for endometrioma and those who did not. CONCLUSION: Current evidence suggests that women with endometriosis-related infertility have similar cycle outcomes to other patients going through ART. It is pertinent for clinicians to assess the risks of surgical intervention on ovarian reserve prior to initiating therapy.

Markers of the p53 pathway further refine molecular profiling in high-risk endometrial cancer: A TransPORTEC initiative.

BACKGROUND: The morphological classification of high-risk endometrial cancer is of limited prognostic value. Recent attempts to stratify tumours according to molecular signatures have shown considerable promise. Here we attempted to further refine molecular classifications using markers of the p53 pathway. METHODS: We analysed the expression of p53 as well as three downstream markers of the p53 pathway, p21, mdm2 and phospho-p63 (pp63), by immunohistochemistry in a series of 114 endometrial cancers (86 endometrioid, 28 non-endometrioid subtype) with high-risk features (such as high tumour grade and deep myometrial invasion) and correlated results with clinical outcome. The Cancer Genome Atlas (TCGA) data were used to analyse TP63 mutations and copy-number alterations using cBioPortal. TP53 was silenced in two endometrial cancer cell lines to study its effect on p21 and p63. RESULTS: About half of the tumours showed a p53 mutant phenotype and there was a strong negative correlation with p21 expression. Being marker positive for pp63 or mdm2 was associated with a significantly increased likelihood of dying, [hazard ratios 5.93 (95% CI 2.37-7.27) and 7.48 (95% CI 3.04-9.39), respectively]. These findings were seen in both p53 wildtype and p53 mutant tumours. Only 11% of TCGA endometrial cancers had a functional TP63 alteration. Upon silencing of TP53, p21 expression was decreased in one cell line, but no effects on p63 were observed. CONCLUSION: Markers of the p53 pathway improve stratification of endometrial cancers and provide novel insights into the role of this pathway in the disease.