Pregnancy after New Womb, the @UniOfGothenburg Live-Donor Uterus Transplant Project, 2014
Nine women in Sweden have received uterus transplants from living relatives in an experimental fertility project. The patients in this trial headed by Mats Brannstrom of the University of Gothenburg are mostly women in their 30s who had lost their uterus to cancer or were born without one. The series of transplants took off in September 2012, with donors including the mothers and relatives of the recipients. These women will soon try to get pregnant, Brannstrom said in a CBS report. Video by TomoNews US, Published on 13 Feb 2014.
In this procedure, a radical hysterectomy is performed on the donor to remove the uterus, cervix and surrounding blood vessels, which will then be implanted to ensure adequate blood flow needed to sustain the uterus. Since the transplanted womb is not connected to the recipient’s fallopian tubes through which eggs are released, natural fertilisation cannot occur in the uterus. Instead, mature eggs will be extracted from the recipient and implanted to the uterus after performing in vitro fertilisation. When the uterus recipient has carried the fetus to full term, the baby is delivered by Caesarian section. The uterus recipient needs to remain on an extensive anti-rejection drug regimen, and the uterus is expected to be removed after a maximum of two pregnancies so the women can be taken off the anti-rejection drugs.
“Mats has done something amazing and we understand completely why he has taken this route, but we are wary of that approach,” said Dr. Richard Smith, head of the U.K. charity Womb Transplant UK. Smith is trying to raise 500,000 pounds ($823,000) to carry out five operations in Great Britain.
Two uterus transplants in Turkey and Saudi Arabia had failed to produce successful pregnancies. Similar procedures are currently under development in Hungary and the UK..
Risk of endometrial cancer rises with increase in sugar-sweetened drinks
Endometrial cancer is the fourth most common cancer in women, and eighth most common cause of cancer death among women in the United States.
Studies have shown women’s risk of endometrial cancer increases with higher levels of estrogen in the body – for example, increased estrogen due to diethylstilbestrol DES or taking hormone therapy for the symptoms of menopause.
Researchers found that sugar-sweetened beverage intake was associated with an increased risk – up to 78% higher – type I, but not type II of endometrial cancer. However, its association with endometrial cancer is unclear.
Sources: Sugar-Sweetened Beverage Intake and the Risk of Type I and Type II Endometrial Cancer among Postmenopausal Women, Cancer Epidemiology Biomarkers and Prevention, AACR, 22 Nov 2013 – abstract – full PDF
Role of DNA Methylation and Epigenetic Silencing of HAND2 in Endometrial Cancer Development
Using easily accessible body fluids to accurately identify individuals with early stage womb cancer has the potential to change the cancer landscape, a new study suggests.
By collecting swabs from the entrance to the womb – a similar technique to that used in cervical screening – genetic material can be easily analysed for pre-cancer/cancer without the need for an invasive womb biopsy. This technique could be used as a test, or to screen women for womb cancer, possibly saving lives via early detection.
BACKGROUND: Endometrial cancer incidence is continuing to rise in the wake of the current ageing and obesity epidemics. Much of the risk for endometrial cancer development is influenced by the environment and lifestyle. Accumulating evidence suggests that the epigenome serves as the interface between the genome and the environment and that hypermethylation of stem cell polycomb group target genes is an epigenetic hallmark of cancer. The objective of this study was to determine the functional role of epigenetic factors in endometrial cancer development.
METHODS AND FINDINGS: Epigenome-wide methylation analysis of >27,000 CpG sites in endometrial cancer tissue samples (n = 64) and control samples (n = 23) revealed that HAND2 (a gene encoding a transcription factor expressed in the endometrial stroma) is one of the most commonly hypermethylated and silenced genes in endometrial cancer. A novel integrative epigenome-transcriptome-interactome analysis further revealed that HAND2 is the hub of the most highly ranked differential methylation hotspot in endometrial cancer. These findings were validated using candidate gene methylation analysis in multiple clinical sample sets of tissue samples from a total of 272 additional women. Increased HAND2 methylation was a feature of premalignant endometrial lesions and was seen to parallel a decrease in RNA and protein levels. Furthermore, women with high endometrial HAND2 methylation in their premalignant lesions were less likely to respond to progesterone treatment. HAND2 methylation analysis of endometrial secretions collected using high vaginal swabs taken from women with postmenopausal bleeding specifically identified those patients with early stage endometrial cancer with both high sensitivity and high specificity (receiver operating characteristics area under the curve = 0.91 for stage 1A and 0.97 for higher than stage 1A). Finally, mice harbouring a Hand2 knock-out specifically in their endometrium were shown to develop precancerous endometrial lesions with increasing age, and these lesions also demonstrated a lack of PTEN expression.
CONCLUSIONS: HAND2 methylation is a common and crucial molecular alteration in endometrial cancer that could potentially be employed as a biomarker for early detection of endometrial cancer and as a predictor of treatment response. The true clinical utility of HAND2 DNA methylation, however, requires further validation in prospective studies. Please see later in the article for the Editors’ Summary.