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Category Archives: Human Reproduction
Uterus transplantation in a non-human primate: long-term follow-up after autologous transplantation
BACKGROUND
Uterus transplantation (UTx) may provide the first available treatment for women affected by uterine infertility. The present study aimed to further develop a surgical technique for autologous UTx in a non-human primate species and to assess long-term function.
METHODS
Female baboons (n= 16) underwent autologous transplantation of the uterus with the Fallopian tubes and ovaries, performed with a previously published surgical technique (n= 6, Group 1) or using a modified technique (n= 10; Group 2). The uterine arteries were dissected to the proximal end of the anterior branch (Group 1) or the entire (Group 2) internal iliac artery, and the ovarian veins were dissected to the crossing over the ureter (Group 1) or further cranially to include greater lengths and patches of the cava/renal vein (Group 2). Back-table preparation created common venous and arterial ends with arterial anastomosis either end-to-side to the left external iliac artery (Group 1) or end-to-end to the left internal iliac artery (Group 2).
RESULTS
Overall short-time survival of the animals was 88% (66% in Group 1 and 100% in Group 2). Of all the operated animals, 75% (66% in Group 1 and 80% in Group 2) resumed ovarian cyclicity. Regular menstruation after UTx was demonstrated only in Group 2 (60%). Menstruating animals (n= 6) were each exposed to timed mating for ≥5 menstrual cycles, but pregnancy did not occur. Adhesions and tubal blockage were seen in post-mortem analysis.
CONCLUSIONS
The modified UTx model of Group 2 is a safe procedure and shows resumed long-term uterine function in a majority of the animals, although pregnancy could not be demonstrated.
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Pharmaceutical thrombosis prophylaxis, bleeding complications and thromboembolism in a national cohort of hysterectomy for benign disease
BACKGROUND
Pharmaceutical thrombosis prophylaxis (PTP) with low-molecular-weight heparin (LMWH) is highly effective in preventing venous thromboembolic events (VTEs) and fatal pulmonary embolism. Important risk factors for VTEs are surgery and immobilization, along with malignancy. Many studies involving gynaecological malignancies show no increased risk for bleeding complications with PTP. Little is known about the PTP-associated risk for bleeding complications with hysterectomy for benign disease, or about current VTE incidence in the less-invasive hysterectomy methods.
METHODS
Our observational prospective national 1-year cohort from 1 January to 31 December 2006 in 53 hospitals represented 79.4% (5297 of 6645) of hysterectomies performed for benign cause in Finland in 2006. We evaluated PTP use and VTE incidence. Operative and post-operative bleeding complications were analysed with logistic regression adjusted for confounders: age, BMI, experience of the gynaecological surgeon, hospital type, indication for hysterectomy, uterine weight, operative haemorrhage, concomitant surgery, adhesiolysis and antibiotic prophylaxis.
RESULTS
Hysterectomies were performed by three main approaches: 2345 vaginal hysterectomies (VHs, 44%), of which 1433 were for uterine prolapse and 912 for other indications, 1679 laparoscopic hysterectomies (LHs, 32%) and 1255 abdominal hysterectomies (AHs, 24%). PTP was given to 64.8% of patients (3420 of 5279) and was identified as LMWH in 3313 patients (97%); 107 left unidentified. By type of hysterectomy, PTP was given in VH for uterine prolapse to 73.2% of patients, VH for other indication to 51.6%, in LH to 59.4% and in AH to 71.9%. For all hysterectomies analysed together, PTP doubled the odds for post-operative haemorrhage or haematoma. By type of hysterectomy, PTP associated with post-operative haemorrhage or haematoma in VH for prolapse [2.7% of PTP given, versus 0.8% of no PTP; odds ratio (OR): 4.82, 95% confidence interval (CI): 1.38–16.83]; and in AH (3.1% versus 1.4%; OR: 2.87, 95% CI: 1.03–7.98), and in AH also with post-operative transfusion (3.1% versus 1.4%; OR: 3.34, 95% CI: 1.41–7.88). For LH and VH for indications other than prolapse, the effect of PTP on post-operative haemorrhage was non-significant. For VH, the risk for post-operative haemorrhage fell with age. Operative mean haemorrhage with all hysterectomy types, and operative bleeding complications in AH and VH also fell with age. Obesity increased haemorrhage and operative bleeding complications for LH and VH, whereas post-operative bleeding complications were less for the obese in AH. VTEs were 6 of 5279 (0.1%): two PEs each occurred after AH and VH, and two deep venous thromboses after LH.
CONCLUSIONS
With a relatively wide PTP coverage (64.8%), VTEs were rare (0.1%). All affected had received PTP. Analysis of efficacy, meaning interpretation of how many VTEs or deaths were prevented, cannot be done from our observational study but related to safety in hysterectomy for benign disease, PTP associated with post-operative bleeding complications with AH and with VH for prolapse.
Trial registration number: ClinicalTrials.gov protocol (NCT00744172).
Posted in Human Reproduction
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The clinical features and management of perineal endometriosis with anal sphincter involvement: a clinical analysis of 31 cases
BACKGROUND
The aim of this study was to investigate the appropriate measures for diagnosing and treating perineal endometriosis (PEM) with anal sphincter involvement.
METHODS
Between January 1992 and April 2011, the clinical features, diagnosis and management of 31 patients who were diagnosed with PEM with anal sphincter involvement at the Peking Union Medical College Hospital were retrospectively analyzed using their clinical records. A range of 6–78 months of outpatient follow-up after surgery were conducted for these 31 patients but was extended by telephone interviews with 29 patients conducted in December 2011.
RESULTS
All 31 patients had a history of vaginal delivery. The level of serum CA125 was elevated in only 2 (6.5%) cases. All cases received surgical treatment, which included narrow excision (NE, close to the edge of the endometrioma) with primary sphincteroplasty (PSp) for 30 cases and incomplete excision (IE) for 1 case. Of the 30 cases in the NE group, 20 (66.7%) received hormone therapy preoperatively. Up until December 2011, there was one recurrence (3.6%) of PEM in the NE group. PEM relapse occurred in the IE patient 6 years after the initial IE surgery. Perineal abscesses were found in one patient post-operatively. No complaint of dyspareunia and no fecal incontinence episodes were observed during follow-up.
CONCLUSIONS
Based on our own experience, NE and PSp may be indicated for the treatment of PEM with anal sphincter involvement.
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Impact of intraperitoneal pressure of a CO2 pneumoperitoneum on the surgical peritoneal environment
BACKGROUND
Animal experiments have suggested that a high intraperitoneal pressure (IPP) might adversely affect the surgical peritoneal environment. The present experimental study investigates the impact of IPP of a CO2 pneumoperitoneum on human peritoneum.
METHODS
Patients undergoing laparoscopic surgery were subjected to either low (8 mmHg) or standard (12 mmHg) IPP. Normal peritoneum was collected from the parietal wall at the beginning of surgery and every 60 min thereafter. Expression levels of 168 genes that encode extracellular matrix proteins, adhesion molecules or inflammatory cytokine signaling molecules were measured in peritoneal tissues using real-time polymerase chain reaction (PCR)-based assay panels. Human peritoneal mesothelial cells (HPMCs) and human peritoneal fibroblasts (HPFBs) were incubated in a CO2 insufflation chamber for 1 h at 12 or 8 mmHg. Hyaluronan (HA) synthesis and mRNA expression levels of hyaluronic acid synthases (HAS) and hyaluronidases (Hyal) in HPMCs and HPFBs were measured at 0, 4, 8, 12, 24 and 48 h after CO2 gas exposure by ELISA and real-time PCR, respectively.
RESULTS
Expression levels of connective tissue growth factor (CTGF), matrix metalloproteinase-9, E-selectin, chemokine (C-X-C motif) ligand 2 (CXCL-2), Hyal-1 and Hyal-2 were significantly higher and those of HAS-1, HAS-3, thrombospondin-2 (TSP-2) and interleukin-10 were significantly lower in the 12 mmHg group compared with the 8 mmHg group. HA synthesis was significantly lower in the 12 mmHg group compared with the 8 mmHg group in HPMCs and HPFBs throughout the time course.
CONCLUSIONS
A low IPP (8 mmHg) may be better than the standard IPP (12 mmHg) to minimize the adverse impact on the surgical peritoneal environment during a CO2 pneumoperitoneum.
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Emotional and relational aspects of egg-sharing: egg-share donors’ and recipients’ feelings about each other, each others’ treatment outcome and any resulting children
BACKGROUND
This paper presents finding from a study of the emotional and relational aspects of egg-sharing, exploring egg-share donors' and recipients' thoughts and feelings about each other, about each other's treatment outcome and any resulting children, as well as their attitudes towards disclosure of donor origins and contact between donors and donor offspring in the future. It is the first study of this population since the removal of donor anonymity in 2005.
METHODS
A paper or online questionnaire was completed anonymously by 48 donors and 38 recipients who took part in egg-sharing between 2007 and 2009. Data were obtained on a range of measures—including demographics, family circumstances, motivations and anxieties, feelings about egg-sharing, retrospective assessments and views on regulation—and analysed to facilitate cross-group and within-group comparisons of donors and recipients.
RESULTS
This study found very few differences between donors and recipients, as well as between successful and unsuccessful egg-share participants. Donors and recipients expressed sentiments of goodwill towards one another, and displayed attitudes of openness regarding disclosure decisions and future contact among donors and donor-conceived offspring. While some donors and recipients wanted to know the outcome of their donor's/recipient's treatment, others preferred not to.
CONCLUSIONS
Most significantly, concerns voiced regarding the potential psychological harm to donors, particularly those whose own treatment ends unsuccessfully, were not borne out by the data.
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Paired-box gene 2 is down-regulated in endometriosis and correlates with low epidermal growth factor receptor expression
BACKGROUND
Paired-box 2 (Pax2) is involved in the development of the female genital tract and has been associated with endometrial pathologies. The expression of Pax2 is induced by epidermal growth factor (EGF) and estrogens. In the present study, Pax2 expression and regulation were investigated in endometriosis.
METHODS AND RESULTS
Pax2 protein expression was assessed by immunohistochemistry in the eutopic (i.e. inside the uterus) and ectopic tissue (endometriosis) from 11 patients. Immunoreactivity was high in the endometrium, with strong epithelial and weaker stromal staining. Similar expression patterns of Pax2 were observed in the endometrium of women without endometriosis (n = 12). The mRNA level of Pax2 was assessed by real-time PCR in the eutopic and ectopic endometria of 14 patients and in the endometrium from women without endometriosis (n = 20). Pax2 expression was lower in endometriotic lesions than that in the eutopic endometrium of patients (P< 0.001) and controls (P= 0.007). Three possible mechanisms determining low Pax2 expression were investigated: EGF signalling, CpG DNA methylation of the Pax2 promoter and steroid response. The mRNA level of the EGF receptor (EGFR1) was assessed in the samples used for Pax2 mRNA assessment. A significant correlation between EGFR1 and Pax2 in both eutopic and ectopic tissues was observed (R = 0.58; slope regression line, 0.81; 95% CI: 0.09–1.52 and R = 0.54; slope regression line, 2.51; 95% CI: 0.02–4.99, respectively). CpG DNA methylation was analyzed by methyl-specific PCR in two regions of the Pax2 promoter but they were unmethylated in all samples. Steroid responsiveness was assessed using endometrial explant cultures and Pax2 was not regulated by either 17β-estradiol or progesterone.
CONCLUSIONS
In endometriosis patients, Pax2 is down-regulated in the lesions compared with the eutopic tissue, possibly due to low EGF signalling.
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