A Multicenter International Temporal and External Validation Study of the Ultrasound-based Endometriosis Staging System.

STUDY OBJECTIVE: The aim of this study was to validate temporally and externally the ultrasound-based endometriosis staging system (UBESS) to predict the level of complexity of laparoscopic surgery for endometriosis. DESIGN: A multicenter, international, retrospective, diagnostic accuracy study was carried out between January 2016 and April 2018 on women with suspected pelvic endometriosis. SETTING: Four different centers with advanced ultrasound and laparoscopic services were recruited (1 for temporal validation and 3 for external validation). PATIENTS: Women with pelvic pain and suspected endometriosis. INTERVENTIONS: All women underwent a systematic transvaginal ultrasound and were staged according to the UBESS system, followed by classification of laparoscopic level of complexity according to the Royal College of Obstetricians and Gynaecologists (RCOG) levels 1 to 3. MEASUREMENTS AND MAIN RESULTS: UBESS I, II, and III were then correlated with RCOG levels 1, 2, and 3, respectively. A comparison between temporal and external sites (skipping "A") and between each site was performed in terms of the diagnostic accuracy of UBESS to predict RCOG laparoscopic skill level. A total of 317 consecutive women who underwent laparoscopy with suspected endometriosis were included. Complete transvaginal ultrasound and laparoscopic surgical outcomes were available for 293/317 (92.4%). At the temporal site, the accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of UBESS I to predict RCOG level 1 were 80.0%,73.8%, 94.9%, 97.2%, 60.2%, 14.5%, and 0.3%, respectively; of UBESS II to predict RCOG level 2 were 81.0%, 70.6%, 82.0%, 26.7%, 96.8%, 3.9%, and 0.3%, respectively; of UBESS III to predict RCOG level 3 were 91.0%, 85.7%, 92.4%, 75.0%, 96.1%, 11.3%, and 0.2%, respectively. At the external sites, the results of UBESS I to predict RCOG level 1 were 90.3%, 92.0%, 88.4%, 90.2%, 90.5%, 7.9%, and 0.1% respectively; UBESS II to predict RCOG level 2 were 89.2%, 100.0%, 88.5%, 37.5%, 100.0%, 8.7%, and 0.0%, respectively; and UBESS III to predict RCOG level 3 were 86.0%, 67.6%, 98.2%, 96.2%, 82.1%, 37.8%, and 0.3%, respectively. When patients requiring ureterolysis (i.e., RCOG level 3) in the absence of bowel endometriosis were excluded (n = 54), the sensitivity of UBESS III to correctly classify RCOG level 3 increased from 85.7% to 96.7% at the temporal site (n = 42) and from 67.6% to 96.0% at the external sites (n = 12) (p <.005). CONCLUSION: The results from this external validation study suggest that UBESS in its current form is not generalizable unless there is either or both bowel deep endometriosis and cul-de-sac obliteration present. The major limitation appears to be the misclassification of women who require surgical ureterolysis in the absence of bowel endometriosis.

Anterior approach to laparoscopic uterine artery ligation.

Herein is described an anterior approach to uterine artery ligation during laparoscopic myomectomy and total laparoscopic hysterectomy. The anterior leaf of the broad ligament is opened and the uterine artery is clipped lateral to its crossing over the ureter. Outcome measures were completion of the procedure laparoscopically and the need for transfusion postoperatively. Thirty-eight myomectomies and 28 difficult total laparoscopic hysterectomies (primarily uteri with large myomas) were performed, with 1 conversion to laparotomy during myomectomy and 1 during hysterectomy, and 1 transfusion after total laparoscopic hysterectomy. The anterior approach to uterine artery ligation is an alternative method for treatment of uterine artery occlusion during laparoscopic myomectomy or hysterectomy performed to treat large myomas.

Synechia after uterine compression sutures.

We present a study of 37 women who underwent uterine compression suture for postpartum hemorrhage, with 13 postoperative assessments by hysteroscopy. Synechia occurred in seven patients, of whom three had Asherman syndrome (23% of women who desired pregnancy and had hysteroscopic evaluation) that could not be corrected.

Hypodysfibrinogenaemia due to production of mutant fibrinogen alpha-chains lacking fibrinopeptide A and polymerisation knob 'A'.

Inherited disorders of fibrinogen are rare and affect either the quantity (hypofibrinogenaemia and afibrinogenaemia) or the quality of the circulating fibrinogen (dysfibrinogenaemia) or both (hypodysfibrinogenaemia). Extensive allelic heterogeneity has been found for all these disorders: in congenital afibrinogenaemia for example more than 40 mutations, the majority in FGA , have been identified in homozygosity or in compound heterozygosity. Numerous mutations have also been identified in patients with hypofibrinogenaemia, many of these patients are in fact heterozygous carriers of afibrinogenaemia mutations. Despite the number of genetic analyses performed, the study of additional patients still allows the identification of novel mutations. Here we describe the characterization of a novel FGA intron 2 donor splice-site mutation (Fibrinogen Montpellier II) identified in three siblings with hypodysfibrinogenaemia. Functional analysis of RNA produced by the mutant minigene in COS-7 cells revealed that the mutation led to the in-frame skipping of exon 2. Western blot analysis of COS-7 cells expressing an exon 2 deleted FGA cDNA revealed that an alpha-chain lacking exon 2, which codes in particular for fibrinopeptide A and polymerisation knob 'A', has the potential to be assembled into a hexamer and secreted. Analysis of precipitated fibrinogen from patient plasma showed that the defect leads to the presence in the circulation of alpha-chains lacking knob 'A' which is essential for the early stages of fibrin polymerisation. Fibrin made from purified patient fibrinogen clotted with thrombin displayed thinner fibers with frequent ends and large pores.

Endometriosis and in vitro fertilisation: a review.

This review aims to evaluate whether severe endometriosis has an impact on the outcome of in vitro fertilisation (IVF), whether IVF is associated with specific complications in this context, whether a specific ovarian stimulation protocol is most appropriate, whether the endometrial condition progresses following ovarian stimulation, and whether endometrial cysts pose a specific problem for IVF. In patients with severe endometriosis, IVF represents an effective treatment option for infertility, as a complement to surgery. The prognostic parameters of IVF are identical to those of other patients. However, the risks related to the severity of endometriosis, particularly the risk of ovarian deficiency, need to be considered. Because of this issue, to which endometriosis-related pain often adds, IVF treatment should be initiated as early as possible, using appropriate protocols and after having fully informed the patient about the specific oocytes retrieval-related risks.

Oocyte recovery post human follicular fluid centrifugation in modified natural cycle and achieving embryo.

This case reports a successful live birth by intracytoplasmic sperm injection (ICSI) following human follicular fluid (HFF) centrifugation for oocyte retrieval in the modified natural cycle of a poor responder patient. A 37-year-old patient presenting with a severe ovarian defect underwent a modified natural cycle with HFF centrifugation prior to ICSI. As there was only one oocyte under direct binocular observation, HFF was centrifuged and a second oocyte was collected. ICSI was performed on both oocytes. Embryo quality and outcome were not compromised by HFF centrifugation. A live birth was achieved in April 2008. In a modified natural cycle, HFF centrifugation avoided loss of oocytes, optimized the IVF treatment, and achieved the development of two embryos.

Total fertilization failure and molecular abnormalities in metaphase II oocytes.

Total fertilization failures (TFF) are rare events of IVF by intracytoplasmic sperm injection (ICSI). When male factor is excluded, the lack of identifiable aetiological criteria raises the question of the reliable clinical management. The goal of this study was to identify molecular abnormalities in metaphase II (MII) oocytes yielding TFF. The nuclear mature MII oocytes mRNA expression profiles were compared between a 30-year-old patient who had experienced three successive TFF (egg number = 39) and control patients with fertile cohorts diagnosed with tubal or male infertility. The mRNA abundance for the 30,000 genes of the genome was evaluated by microarray and, for selected genes, by quantitative-polymerase chain reaction analysis. Transcriptional analysis of unfertilized MII oocytes revealed an altered gene expression profile associated with TFF. Meiosis, cell growth and apoptosis controlling genes were mis-expressed with important fold changes. The results reveal that, despite passing the pre-IVF morphological examination, high-grade oocytes may carry substantial molecular abnormalities at the gene expression level associated with failure of MII oocyte activation. In the absence of an identifiable defect causing TFF, this microarray approach allows improvement of clinical therapeutic management: informed counselling about alternate therapeutic solutions could be proposed.

Optimal timing of ultrasonographic and Doppler evaluation of uterine receptivity to implantation.

In IVF programmes, transvaginal ultrasonography is used as a non-invasive method to evaluate uterine receptivity. The aim of this study was to determine when to perform this investigation in order to optimize prediction of the likelihood of pregnancy. Over 9 months, 124 patients undergoing IVF or intracytoplasmic sperm injection were studied. The ultrasonographic evaluation included endometrial thickness, endometrial pattern, uterine artery pulsatility index, protodiastolic notch, end-diastolic blood flow, and endometrial-subendometrial blood flow distribution pattern. All patients underwent ultrasonographic investigation on the days of human chorionic gonadotrophin (HCG) administration, oocyte retrieval, and embryo transfer. Statistical analysis was done using recursive-partitioning analysis. The pregnancy and implantation rates per transfer were 33 and 19.8% respectively. In terms of single parameters, women with an end-diastolic blood flow, an endometrial-subendometrial blood flow and a multilayered endometrium were more likely to be pregnant than women without one or more of these signs. The most effective combination for evaluation of uterine receptivity was end-diastolic blood flow, endometrial pattern and endometrial thickness. Sensitivity and specificity of this combination were around 81%, positive predictive value was 68.2%, and negative predictive value 89.7%. The best sensitivity and specificity were obtained on the day of HCG administration: respectively 81.1 and 81.3%.

The human cumulus--oocyte complex gene-expression profile.

BACKGROUND: The understanding of the mechanisms regulating human oocyte maturation is still rudimentary. We have identified transcripts differentially expressed between immature and mature oocytes and cumulus cells. METHODS: Using oligonucleotide microarrays, genome-wide gene expression was studied in pooled immature and mature oocytes or cumulus cells from patients who underwent IVF. RESULTS: In addition to known genes, such as DAZL, BMP15 or GDF9, oocytes up-regulated 1514 genes. We show that PTTG3 and AURKC are respectively the securin and the Aurora kinase preferentially expressed during oocyte meiosis. Strikingly, oocytes overexpressed previously unreported growth factors such as TNFSF13/APRIL, FGF9, FGF14 and IL4 and transcription factors including OTX2, SOX15 and SOX30. Conversely, cumulus cells, in addition to known genes such as LHCGR or BMPR2, overexpressed cell-to-cell signalling genes including TNFSF11/RANKL, numerous complement components, semaphorins (SEMA3A, SEMA6A and SEMA6D) and CD genes such as CD200. We also identified 52 genes progressively increasing during oocyte maturation, including CDC25A and SOCS7. CONCLUSION: The identification of genes that were up- and down-regulated during oocyte maturation greatly improves our understanding of oocyte biology and will provide new markers that signal viable and competent oocytes. Furthermore, genes found expressed in cumulus cells are potential markers of granulosa cell tumours.

Extracorporeal membrane oxygenation therapy for circulatory arrest due to postpartum hemorrhage.

BACKGROUND: Cardiac arrest after postpartum hemorrhage may not respond to advanced life support. Various resuscitation methods have been proposed, including sternotomy and direct cardiac massage. Extracorporeal membrane oxygenation (ECMO) might be an alternative. CASE: We report the case of a woman who suffered atonic uterine hemorrhage perioperatively after cesarean delivery of twins. During initial conservative treatment using prostaglandin analog (sulprostone), cardiac decompensation developed and was followed by cardiopulmonary arrest. Circulatory failure remained unresponsive after 2 hours of resuscitation, when ECMO was initiated. The ensuing recovery was favorable. CONCLUSION: Aggressive mechanical circulatory support, such as ECMO, should be considered in a case of potentially reversible cardiocirculatory failure in a young obstetric patient.

Obesity does not adversely affect results in patients who are undergoing in vitro fertilization and embryo transfer.

OBJECTIVE: To examine the outcome of in vitro fertilization according to the body mass index of infertile patients. STUDY DESIGN: Between September 2003 and May 2005, 573 patients underwent 789 in vitro fertilization cycles or ICSI because of male factor, tubal factor, and unexplained infertility were retrospectively included from our IVF database. The patients were classified in four groups: BMI<20 kg/m2 (264 cycles), 20< or = BMI<25 (394 cycles), 25< or = BMI < 30 (83 cycles), and BMI> or = 30 (48 cycles). All patients had a long protocol for IVF with a combination of the GnRH agonist and recombinant FSH. RESULTS: All parameters of ovarian response were comparable except the total required r-FSH dose. This dose was statistically higher in the group of BMI> or = 30 compared to the other groups (p = 0.0003). All parameters of IVF outcome were comparable, including the cancellation rate, the implantation rate, and pregnancy rates. CONCLUSION: Obese patients require a higher r-FSH dose to achieve follicular maturation than normal weight patients. Obesity does not affect negatively results of in vitro fertilization.

Amenorrhoea revealing an arteriovenous uterine malformation, and recovery of menses after embolization.

A case is reported of secondary amenorrhoea related to an arteriovenous malformation (AVM) successfully treated with embolization, with a recovery of menstrual cycles. A 28-year-old woman presented with secondary amenorrhoea as the only clinical symptom. Although she had an eugonadic status, there was no genital withdrawal bleeding upon cessation of an oral contraceptive. Pelvic transvaginal ultrasonography revealed a pelvic mass but magnetic resonance imaging (MRI) clearly showed an AVM. Classical angiography was performed with endovascular embolization. Partial thrombosis of the lesion was assessed by magnetic resonance angiography. Recovery of menses occurred 2 months later. It is speculated that blood stolen from the endometrium by the uterine AVM could have been responsible for the amenorrhoea. It is a very unusual cause, and it can be successfully treated with embolization.