Reproductive outcomes of patients with T-Shaped and septate uterus following metroplasty: an observational study.

INTRODUCTION: Uterine malformations are common and may contribute to infertility and adverse pregnancy outcomes. After an accurate diagnosis, correcting the abnormal uterine morphology is the main goal to optimize reproductive outcomes. The principal objective of this study was to assess the impact of metroplasty for T-shaped (U1a) and septate uteri (U2) on live birth rates in infertile patients. METHODS: This was a prospective observational study of infertile women with either U1a or U2 uterine anomaly. Patients with unexplained infertility and repeated (IVF/ICSI) failure were included. Hysteroscopic metroplasty was performed by a single experienced surgeon. Fertility outcomes of all cases were evaluated prospectively evaluated. The main outcome parameter was a live birth rate either achieved spontaneously or with assisted conception. RESULTS: A total of 48 patients were included in U1a group and bilateral longitudinal uterine-lateral wall incision was carried out. A total of 63 patients were included in the U2 group and septum incision was carried out, 60 out of these 63 patients with U2 uterine anomaly required further lateral wall incision during septoplasty. During the first 12 months following surgery, nearly half of the patients in both groups achieved spontaneous pregnancy; 45% in the U1a group and 39% in the U2 group delivered at term. CONCLUSIONS: Hysteroscopic metroplasty offers promising reproductive outcomes in the presence of U1a and U2 uterine anomalies for those with unexplained infertility and repeated IVF/ICSI failures. In addition, uterine septum cases should be carefully evaluated intra-operatively to detect and repair concurrent lateral uterine wall anomalies.

Correction: Heterogeneity of endometriosis lesions requires individualisation of diagnosis and treatment and a different approach to research and evidence based medicine.

Statistical significance is used to analyse research findings and is together with biased free trials the cornerstone of evidence based medicine. However traditional statistics are based on the assumption that the population investigated is homogeneous without smaller hidden subgroups. The clinical, inflammatory, immunological, biochemical, histochemical and genetic-epigenetic heterogeneity of similar looking endometriosis lesions is a challenge for research and for diagnosis and treatment of endometriosis. The conclusions obtained by statistical testing of the entire group are not necessarily valid for subgroups. The importance is illustrated by the fact that a treatment with a beneficial effect in 80% of women but with exactly the same but opposite effect, worsening the disease in 20%, remains statistically highly significant. Since traditional statistics are unable to detect hidden subgroups, new approaches are mandatory. For diagnosis and treatment it is suggested to visualise individual data and to pay specific attention to the extremes of an analysis. For research it is important to integrate clinical, biochemical and histochemical data with molecular biological pathways and genetic-epigenetic analysis of the lesions.

Heterogeneity of endometriosis lesions requires individualisation of diagnosis and treatment and a different approach to research and evidence based medicine.

Statistical significance is used to analyse research findings and is together with biased free trials the cornerstone of evidence based medicine. However traditional statistics are based on the assumption that the population investigated is homogeneous without smaller hidden subgroups. The clinical, inflammatory, immunological, biochemical, histochemical and genetic-epigenetic heterogeneity of similar looking endometriosis lesions is a challenge for research and for diagnosis and treatment of endometriosis. The conclusions obtained by statistical testing of the entire group are not necessarily valid for subgroups. The importance is illustrated by the fact that a treatment with a beneficial effect in 80% of women but with exactly the same but opposite effect, worsening the disease in 20%, remains statistically highly significant. Since traditional statistics are unable to detect hidden subgroups, new approaches are mandatory. For diagnosis and treatment it is suggested to visualise individual data and to pay specific attention to the extremes of an analysis. For research it is important to integrate clinical, biochemical and histochemical data with molecular biological pathways and genetic-epigenetic analysis of the lesions.

Uterine transplantation.

Successful human uterine transplantation followed by subsequent pregnancy and live birth in a woman for whom this would otherwise have been impossible is a laudable goal. Research programs have been developed in several countries aimed at achieving this goal. The pioneering Swedish program has reported live births in six women, two of whom had a second pregnancy and birth. Five other live births have been reported from other countries. Most transplants were from a live donor, although recently a live birth has been reported following transplant from a deceased donor. The surgical procedure on a live donor is highly invasive, complex, hazardous, and long and may decrease her quality of life. The use of a deceased donor would partly simplify this issue and is being explored in several centers. Also explored are technical modifications to simplify the procedure and shorten the operating times. The American Society for Reproductive Medicine (ASRM) reminds us of the full array of options available to patients: 'including gestational carriers (surrogacy), adoption and child-free living'. The ASRM also recommends 55 years as the upper age limit for transfer of donor oocytes and embryos in healthy women. Would it not be more practical and less onerous for the prospective live donor to carry the pregnancy instead? Uterine transplantation remains an experimental procedure that requires the study and resolution of ethical, technical, financial, and social issues, all very important.

Infection as a potential cofactor in the genetic-epigenetic pathophysiology of endometriosis: a systematic review.

BACKGROUND: The genetic-epigenetic theory postulates that endometriosis is triggered by a cumulative set of genetic-epigenetic (GE) incidents. Pelvic and upper genital tract infection might induce GE incidents and thus play a role in the pathogenesis of endometriosis. Thus, this article aims to review the association of endometriosis with upper genital tract and pelvic infections. METHODS: Pubmed, Scopus and Google Scholar were searched for 'endometriosis AND (infection OR PID OR bacteria OR viruses OR microbiome OR microbiota)', for 'reproductive microbiome' and for 'reproductive microbiome AND endometriosis', respectively. All 384 articles, the first 120 'best match' articles in PubMed for 'reproductive microbiome' and the first 160 hits in Google Scholar for 'reproductive microbiome AND endomytriosis' were hand searched for data describing an association between endometriosis and bacterial, viral or other infections. All 31 articles found were included in this manuscript. RESULTS: Women with endometriosis have a significantly increased risk of lower genital tract infection, chronic endometritis, severe PID and surgical site infections after hysterectomy. They have more colony forming units of Gardnerella, Streptococcus, Enterococci and Escherichia coli in the endometrium. In the cervix Atopobium is absent, but Gardnerella, Streptococcus, Escherichia, Shigella, and Ureoplasma are increased. They have higher concentrations of Escherichia Coli and higher concentrations of bacterial endotoxins in menstrual blood. A Shigella/Escherichia dominant stool microbiome is more frequent. The peritoneal fluid of women with endometriosis contains higher concentrations of bacterial endotoxins and an increased incidence of mollicutes and of HPV viruses. Endometriosis lesions have a specific bacterial colonisation with more frequently mollicutes (54%) and both high and medium-risk HPV infections (11%). They contain DNA with 96% homology with Shigella. In mice transplanted endometrium changes the gut microbiome while the gut microbiome influences the growth of these endometriosis lesions. CONCLUSIONS: Endometriosis is associated with more upper genital tract and peritoneal infections. These infections might be co-factors causing GE incidents and influencing endometriosis growth.

Laparoscopic excision of posterior vaginal fornix in the treatment of patients with deep endometriosis without rectum involvement: surgical treatment and long-term follow-up.

BACKGROUND: The objective of the study is to evaluate the short- and long-term efficacy of complete laparoscopic excision of deep endometriosis, without rectum involvement, with the opening and partial excision of the posterior vaginal fornix. METHODS: Thirty-one patients were included in the study with symptomatic extensive disease including involvement of the cul-de-sac, rectovaginal space and posterior vaginal fornix without rectum involvement. Endoscopic surgery was performed with complete separation of rectovaginal space and in-block resection of the diseased tissue, opening and partial excision of the posterior vaginal fornix and vaginal closure either by laparoscopic or by vaginal route. Patients filled in questionnaires on pain before and 12, 24, 36, 48 and 60 months after surgical treatment. RESULTS: No intraoperative complications were observed; 65% were free of analgesic on post-operative day 2, 38% had total remission of chronic pain and 22% were improved; 38% had total remission of dysmenorrhoea and 22% were improved; 45% had total remission of dyspareunia and 25% were improved. Follow-up improvement of symptoms was statistically significant and was maintained for 5 years without recurrence of the disease or repeated surgery (P < 0.001). CONCLUSION: Complete surgical resection of deep infiltrative endometriosis with excision of the adjacent tissue of the posterior vaginal fornix improves quality of life with persistence of results for long time in patients not responsive to medical treatment.

Reproductive surgery.

The aim of this review is to try and answer the following questions. What is the importance of reproductive surgery? What does the field encompass? What are the deleterious effects of postoperative adhesions in reproductive age women? Is there a relationship between the mode of surgical access, laparoscopy versus laparotomy, and the degree of postoperative adhesions? What is microsurgery and what is its place in reproductive surgery? Does training in microsurgery provide benefits to the gynecologist and his/her patients? At present, when assisted reproductive techniques have recorded enormous progress and the technology has been industrialized, what is the place of reconstructive tubal surgery in the treatment of tubal infertility?

C-reactive protein should accelerate the diagnosis of bowel injury after gynecologic surgery.

STUDY OBJECTIVE: To search for a marker that could aid in earlier diagnosis of bowel injury after gynecologic surgery. DESIGN: Retrospective case study with prospective controls (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Fourteen women with bowel injuries and 50 controls with no postoperative complications. MEASUREMENTS AND MAIN RESULTS: Bowel injury occurred in 14 (2.4/1000) of 5901 gynecologic procedures. Of these, eight were recognized intraoperatively and treated immediately. In six women C-reactive protein levels were markedly increased (>100 mg/L) relative to control patients (p <0.0001). CONCLUSION: Systematic postoperative assessment of C-reactive protein in patients at high risk for bowel injury may help identify this complication earlier in the postoperative period.

Is routine amniocentesis for advanced maternal age still indicated?

OBJECTIVE: To evaluate a policy of selective rather than routine use of amniocentesis for advanced maternal age. METHOD: A consecutive series of 359 pregnant women aged 38-47 underwent nuchal translucency measurement (NTM) at 10-14 weeks, maternal serum screening (MSS) by alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) at 15-17 weeks, and second trimester ultrasound at 21-23 weeks. Women with NTM <3 mm, MSS-derived risk <1/250, and a normal second trimester sonography were considered at low risk and were suggested not to have an amniocentesis. RESULTS: Either the NTM or MSS test was positive in 130 women; 105 (81%) of them elected to have an amniocentesis, versus 122 (53%) of 229 in whom both tests were negative (p < 0.001). Nineteen (5%) of 359 patients had NTM > or =3 mm; all 7 cases of Down's syndrome were in this group; 122 (34%) of 359 patients had a MSS-derived risk > or =1/250; 6 of the 7 cases of Down's syndrome were in this group: Ten patients had an abnormal second trimester ultrasound, 1 of which had trisomy 18. Of the 219 patients with MSS-derived risk <1/250, a NTM <3 mm, and a normal second trimester ultrasound, none had a baby with a chromosomal abnormality (95% confidence interval: 0-1.4%). CONCLUSION: Amniocentesis may be offered on a selective rather than routine basis in women over 38, based upon the results of noninvasive screening tests.

Hysteroscopic resection of submucosal myomas in patients with infertility.

BACKGROUND: Submucosal myomas are associated with infertility, and may be treated by hysteroscopic resection. Improvement of the menstrual pattern after surgery has been examined and compared with pregnancy rate in a group of menorrhagic women with primary (n = 24) and secondary (n = 35) infertility. METHODS: The entire patient group (n = 59) was managed between January 1990 and September 1998. The submucosal myomas were intracavitary (n = 15), intramural class 1 (n = 34) and intramural class 2 (n = 10), and none was multiple submucosal myoma. The mean (+/- SD) age was 36.6 +/- 4.6 years; mean myoma size was 24.5 +/- 13.3 mm; mean duration of the procedure was 40 +/- 23 min; and mean follow-up was 26 +/- 18.8 months. Thirty-five patients had one or more associated infertility factors. RESULTS: An improvement in clinical symptoms was observed in 62% of patients. Sixteen patients (27%) conceived, and of these only six (10%) delivered at term. The pregnancy rate was significantly better when myoma was the exclusive aetiology of infertility (41.6%), and when the lesion was >/=50 mm in size (57.1%). CONCLUSIONS: Hysteroscopic myomectomy appears safe, and is effective in the control of menstrual disorders. However, the effect on infertility seems limited, particularly in terms of delivery rate. The advanced age of the patients may partly explain these results.

Cross-linked hyaluronate hydrogel prevents adhesion formation and reformation in mouse uterine horn model.

The aim of this study was to evaluate the efficacy of cross-linked hyaluronate hydrogel (HA gel) as an adjuvant for postoperative adhesion prevention, in a mouse uterine horn model. In experiment 1 uterine horns were abrased with iodine. HA gel was applied to the injured surface before closure in the treatment group. In experiment 2, after injuring the uterine horns, three stitches were placed at equal distances around the uterine horns to appose the injured medial surfaces of the two horns during healing. HA gel was inserted between the uterine horns in the treatment group. In experiment 3 prevention of adhesion reformation was assessed. After lysis of adhesions that were induced as in experiment 2, HA gel was introduced between the serosal surfaces of apposing uterine horns. Untreated animals served as controls in each experiment. Statistical analysis was carried out using Student's t-test. The adhesion score was significantly lower in the HA gel group on the 14th day compared with controls in all the experiments: in experiment 1, 0.3 +/- 0.4 versus 1.7 +/- 1.2; in experiment 2, 0.9 +/- 1.0 versus 2.6 +/- 0.5; and in experiment 3, 1.5 +/- 0.9 versus 2.2 +/- 0.6 respectively. Cross-linked HA gel significantly reduced de-novo adhesions (P< 0.03) and adhesion reformation (P < 0.03).

Laparoscopic uterine suspension using three-stitch technique.

We conducted a prospective, longitudinal study to assess the efficacy of a new laparoscopic hysteropexy technique in alleviating pelvic pain. Subjects were 50 women of reproductive age with chronic pelvic pain or dyspareunia in whom the only clinical finding was uterine retroversion who underwent laparoscopic uterine suspension using three-stitch technique. There were no intraoperative complications. The only postoperative complication was abdominal pain in one woman. The technique was effective in relieving symptoms in these patients. Of the 22 women who had associated infertility for longer than 3 years, 10 became pregnant within 1 year after surgery. This benefit, however, is likely due to couples' improved sex life rather than change in surgical axis of the uterus.

Role of microlaparoscopy in the diagnosis of peritoneal and visceral adhesions and in the prevention of bowel injury associated with blind trocar insertion.

OBJECTIVE: To determine the frequency of peritoneal and visceral adhesions to the umbilical region according to past surgical history and to estimate the risk of bowel injury with blind insertion of the principal trocar-cannula. DESIGN: Prospective, unicentric study by a single operator. SETTING: Clinique Saint-Sernin and Polyclinique de Bordeaux, Bordeaux, France. PATIENT(S): Eight hundred fourteen patients undergoing diagnostic or operative laparoscopy were classified into four groups based on their history of abdominal surgery: group I (n = 469), no previous abdominal surgery; group II (n = 125), prior laparoscopic surgery; group III (n = 131), previous laparotomy with a horizontal supra-pubic incision; group IV (n = 89), previous laparotomy with a midline incision. INTERVENTION(S): Initial microlaparoscopy performed through the left upper quadrant of the abdomen, inspection of the anterior abdominal wall and particularly the umbilical area for the presence of adhesions. Patients who had adhesions were assessed as to whether or not they were at significant risk of injury from blind insertion of the principal trocar. MAIN OUTCOME MEASURE(S): Incidence of umbilical adhesions and the potential risk of bowel injury with blind insertion of the umbilical (principal) trocar. RESULT(S): Umbilical adhesions were found in 9.82% of the 814 cases. The rates of umbilical adhesions were as follows: group I, 0.68%; group II, 1.6%; group III, 19.8%; and group IV, 51.7%. Severe adhesions with potential risk of bowel injury with blind insertion of the umbilical trocar in the four groups were 0.42%, 0.80%, 6.87%, and 31.46%, respectively. CONCLUSION(S): Women with previous laparotomy have a higher incidence of umbilical adhesions, especially in case of midline incision. Preliminary inspection of the umbilical area with a microlaparoscope and insertion of the umbilical trocar under direct vision are recommended for patients at risk for adhesions to reduce complications associated with insertion of the principal (umbilical) trocar.

Thermal balloon ablation versus endometrial resection for the treatment of abnormal uterine bleeding.

This study compares the clinical efficacy and safety of a thermal uterine balloon system with hysteroscopic endometrial resection in the treatment of dysfunctional uterine bleeding. In all, 147 women were treated by two experienced gynaecological surgeons: one performed 73 thermal balloon ablations and the other 74 endometrial resections between November 1994 and April 1998. The inclusion criteria were similar in both groups. The operative time was reduced significantly with the uterine balloon technique. There were no intra-operative complications in either group and postoperative morbidities were minimal and not statistically different. Multivariate analysis noted two prognostic factors associated with failures: retroverted uterus with thermal balloon ablation and age under 43 years with endometrial resection. The overall success rate did not differ significantly between the two groups 83.0 +/- 5% for balloon ablation and 76.3 +/- 6% for endometrial resection. Uterine balloon ablation appears to be as efficacious as endometrial resection. The former is much easier to perform, making the technique readily reproducible, especially by those with limited expertise in hysteroscopic surgery, and thus more widely applicable and safer.

Complex uterine surgery: a cooperative role for interventional radiology with hysteroscopic surgery.

OBJECTIVE: To describe the value of concurrent interventional radiology with hysteroscopy for the management of complex intrauterine abnormalities. DESIGN: A new descriptive technique. SETTING: Tertiary care center. PATIENT(S): Three case reports. INTERVENTION(S): Interventional radiology with the placement of guidewires and/or dilatation of resistant structures may assist with hysteroscopic management of complex intrauterine abnormalities or may be a primary therapeutic option. MAIN OUTCOME MEASURE(S): Resolution of dysmenorrhea and restoration of fertility. RESULT(S): The placement of a guidewire into an occluded portion of the intrauterine cavity provides direction and safety for hysteroscopic resolution of the underlying problem. In the last case, placement of the guidewire and passing dilators over the guidewire provided complete treatment. CONCLUSION(S): The uterine cavity or a smaller segment of it may be blocked by occlusive fibrous tissue that is not amenable to standard hysteroscopic dissection. Combining radiologic imaging with hysteroscopic surgery allows visual access to instrumentation and the hidden structures or organs throughout the entire procedure. It adds complexity to the surgery but may allow restoration of function to an organ or structure that is otherwise inaccessible.

A comparative study of the effects of thrombin and electrodesiccation used for haemostasis on inflammation and adhesion formation.

Electrodesiccation or chemical agents, such as thrombin and fibrin sealant, may be used to control oozing in the peritoneal cavity. Electrodesiccation is time consuming and associated with adjacent thermal damage. Adhesion formation remains a concern with the use of thrombin and fibrin sealant. In this study, adhesion formation and various histological parameters of inflammation were evaluated following haemostasis with electromicrodesiccation or thrombin in the rabbit model (n = 36). Following laparotomy, the right uterine horn was subjected to a measured injury producing sufficient oozing. After the injury was effected, the animals were randomized to haemostasis with electromicrodesiccation (n = 18) or thrombin (n = 18). In the first phase of the study, the histological parameters of acute injury and haemostasis with either modality were evaluated in two animals in each group. In the second phase, one, two and 10 animals, in each group, were submitted to second-look laparotomy on post-operative days 2, 7, and 15, respectively and the type and extent of adhesions were quantified. Histological parameters of inflammation as well as the type and extent of adhesions were comparable between the two groups. We conclude that local application of thrombin is not associated with a statistically greater degree of post-operative adhesions when compared to electromicrodesiccation.

The role of laparoscopy in the management of pelvic pain in women of reproductive age.

OBJECTIVE: To review the diagnostic and therapeutic roles of laparoscopy in women of reproductive age with acute and chronic pelvic pain. DATA IDENTIFICATION: Studies relating to the use of laparoscopy in women with acute and chronic pelvic pain were identified through the literature and MEDLINE searches. CONCLUSION(S): Laparoscopy has an important place in the management of conditions that cause acute pelvic pain in women of reproductive age, including ectopic pregnancy, pelvic inflammatory disease, tubo-ovarian abscess, and adnexal torsion. The procedure frequently facilitates the diagnosis and provides the necessary access for surgical treatment. Prompt diagnosis and effective management prevent complications and help preserve fertility. The role of laparoscopy in women with chronic pelvic pain is more controversial and limited, but abnormal laparoscopic findings are detected in approximately 60% of those who have undergone a multidisciplinary investigation and received a tentative clinical diagnosis. The access provided by laparoscopy permits the effective surgical treatment of many of the conditions encountered, including endometriosis, pelvic adhesions, ovarian lesions, and symptomatic uterine retroversion.

A new type of CO2 laser avoids power density loss due to absorption and the blooming effect by the CO2 gas environment.

The aim of this study was to compare the acute tissue effects of a standard CO2 laser (Ultrapulse 5000) with a new design (Ultrapulse 5000L) that utilizes a different carbon isotope (C13) in the rat uterine horn model. Following laparotomy, measured laser injuries were effected with the Ultrapulse 5000 or Ultrapulse 5000L lasers via a laparoscope using CO2 or air for insufflation. Serial sections of the lesions were, thereafter, obtained to evaluate depth and width of total injury, width of defect and thermal damage zone. When CO2 was used as the insufflating gas, Ultrapulse 5000L laser was associated with significantly deeper lesions compared to the Ultrapulse 5000 system for the two tested pulsed energy levels (P < 0.0001). The width of total injury and thermal damage zone were significantly less with the former laser compared to the latter. The width of the defect was, however, significantly larger with the Ultrapulse 5000L laser for the 200 millijoule pulsed energy level, whereas it was comparable for the 75 millijoule level. When air was used as the insufflation gas, all four parameters of tissue injury were comparable between the two types of laser (P > 0.05). The adverse effects on the CO2 laser beam and the resultant altered tissue effects that occur in a regular CO2 environment are avoided by the use of the Ultrapulse 5000L or an air environment.