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.

Reproductive surgery remains an essential element of reproductive medicine.

Background: Reproductive surgery has long been neglected and is perceived to be simple surgery that can be undertaken by all gynaecologists. However, given the ever-expanding knowledge in the field, reproductive surgery now comprises surgical interventions on female reproductive organs that need to be carefully planned and executed with consideration given to the individuals symptoms, function of the organ and fertility concerns. Objectives: To discuss the different perspectives of reproductive surgeons and other gynaecological surgeons, e.g., gynaecological oncologists, and advanced minimally invasive surgeons, regarding diagnosis and management of pelvic pathology that affects reproductive potential. Furthermore, to highlight the gaps in knowledge and numerous controversies surrounding reproductive surgery, while summarising the current opinion on management. Materials and Methods: Narrative review based on literature and the cumulative experience of the authors. Main outcome measures: The paper does not address specific research questions. Conclusions: Reproductive surgery encompasses all reproductive organs with the aim of alleviating symptoms whilst restoring and preserving function with careful consideration given to alternatives such as expectant management, medical treatments, and assisted reproductive techniques. It necessitates utmost technical expertise and sufficient knowledge of the female genital anatomy and physiology, together with a thorough understanding of and respect to of ovarian reserve, tubal function, and integrity of the uterine anatomy, as well as an up-to-date knowledge of alternatives, mainly assisted reproductive technology. What is new?: A holistic approach to infertile women is only possible by focusing on the field of reproductive medicine and surgery, which is unattainable while practicing in multiple fields.

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.

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.

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?

Laparoscopic tubal surgery in infertility.

Besides its diagnostic value, laparoscopy is a useful operative tool in the treatment of infertility. We have used dilatation of phimotic tubal ostia and salpingolysis by laparoscopy as our primary approach. In the total series of 33 cases a pregnancy rate of 42.1 percent was obtained.

Laparoscopic treatment of interstitial pregnancy.

The conventional treatment of interstitial pregnancy has been cornual resection of hysterectomy by laparotomy. We have used a laparoscopic approach to treatment of interstitial pregnancy, consisting of cornual excision in four patients and salpingotomy incision via the myometrium in another. In all five cases, the procedure was associated with minimal bleeding and no complications.

Profile of women requesting reversal of sterilization.

One hundred consecutive patients requesting reversal of sterilization have been analyzed. At the time of sterilization 52% were 25 years old or under and 89% were 30 years old or under. Fifty-three patients were not in a stable marital relationship. The mean number of children per patient was 2.39. Two-thirds of the 47 patients who underwent pueperal sterilization regretted their decision within the 1st year. Twenty-six percent of the patients felt psychologically adversely affected by the procedure. The reason for requesting reversal of sterilization in the majority (63%) was a change in marital status. Other reasons were crib death (17%), desire for more children (10%), psychologic factors (6%) accidental tragedies (4%).

Tubal reanastomosis by microsurgery.

The enormous increase in the number of sterilizations performed in young women is creating a demand for reversal of this procedure. The author's experience with tubal reanastomosis using a microsurgical technique is presented. The traditional approach to cornual occlusion of the tubes has been tubouterine implantation. The demonstration that in such cases the intramural portion of the tube is often patent and that the occlusion site is located in the proximal isthmus has allowed, instead, resection and end-to-end anastomosis at the cornua. Including both tubouterine anastomosis for cornual occlusion and end-to-end anastomosis after previous sterilization, tubal reanastomosis was performed in 31 patients. The postoperative patency rate was 87%, and 64% have had intrauterine pregnancies. In the group subjected to tubal reanastomosis following a previous sterilization, 72.7% of those attempting a pregnancy and having more than 6 months' follow-up have had intrauterine gestations.

Salpingostomy by microsurgery.

Salpingostomy for hydrosalpinx was carried out using a microsurgical technique. The postoperative patency rate was over 90%. Among the 41 patients followed for more than 1 year, 29% have had one or more intrauterine pregnancies and 27% have had live births. The ectopic gestation rate was 12%. All of the tubal gestations occurred in the 1st postoperative year whereas 60% of the intrauterine pregnancies occurred after the 1st year, suggesting a degree of restoration in the mucosa and the musculature of the oviduct with the re-establishment of patency and the passage of time.

Salpingo-ovariolysis by laparoscopy in infertility.

Lysis of periadnexal adhesions (salpingo-ovariolysis) by laparoscopy was performed on 92 infertile patients who subsequently have been followed for at least 9 months. In each instance, the duration of infertility was longer than 20 months. Periadnexal adhesions were severe in most cases and moderate in the remainder. Moreover, only those cases where ovum pickup by the oviduct with the lesser pathology was deemed impossible or greatly hampered were included in this series. There were no significant postoperative complications. Of the total of 92 patients, 57 (62%) achieved at least one intrauterine pregnancy, 54 (58.7%) had one or more full-term pregnancies, and 5 patients (5.4%) had ectopic pregnancies. With appropriately selected patients and in trained hands, laparoscopic salpingo-ovariolysis is a low-risk procedure associated with a surprisingly good success rate. It can be performed on a day-care basis with considerable savings to the patient in terms of both hospital stay and avoidance of major abdominal surgery.

Microsurgical reversal of female sterilization: a reappraisal.

The role of microsurgery in reversal of sterilization has been reassessed and 118 cases reviewed. The technical variations for tubo-tubal anastomosis necessitated by the condition of the oviducts have been outlined in detail. All 118 cases were included in the analysis without requirement for a minimal postoperative trial period. Seventy-six of these (64.4%) had achieved one or more intrauterine pregnancies. There was one ectopic gestation. Forty-seven patients, reported earlier, were resurveyed. These patients had a minimal postoperative trial period of 18 months. Thirty-eight (80.8%) had achieved one or more term pregnancies or were in the latter half of a normally progressing pregnancy. The mean time interval between the reconstructive surgery and the occurrence of pregnancy was 10.2 months. The longest time interval was 40 months. An inverse relationship was noted between the total length of the reconstructed oviducts and the occurrence of pregnancy.

PIP: The role of microsurgery in reversal of sterilization has been reassessed and 118 cases over a 10-year period reviewed. Their ages ranged between 22 and 43 years of age and the interval between sterilization and request for reversal varied from 1 week to 16 years. The technical variations for tubo-tubal anastomosis necessitated by the condition of the oviducts have been outlined in detail. All 118 cases were included in the analysis without requirement for a minimal postoperative trial period. The 2 most prominent reasons for reversal request were a change in marital status (63%) and crib death (17%). 76 of these 118 cases achieved 1 or more intrauterine pregnancies. There was 1 ectopic gestation. No significant complications were reported. 47 patients, reported earlier, were resurveyed. They had had a minimal postoperative trial period of 18 months. The mean interval between reconstruction of tubes and subsequent pregnancy was 10.2 months. The longest interval was 40 months. 38 (80.8%) had achieved 1 or more term pregnancies or were in the latter 1/2 of a normally progressing pregnancy. An inverse relationship was noted between the total length of the reconstructed oviducts and the occurrence of pregnancy. With oviducts that were longer than 6 cm, most of the pregnancies occurred within 5 cycles following the reconstructive surgery. For those patients who conceived during the 1st postoperative cycle, their oviducts measured 5 cm or longer.

Microsurgical transposition of the human fallopian tube and ovary with subsequent intrauterine pregnancy.

This is the report of a case of a single left unicornuate uterus in a woman whose ipsilateral tube and ovary had been removed subsequent to a left tubal pregnancy. On the right side were present an ovary and a short oviduct (composed of infundibulum and ampulla) immobilized high on the pelvic side wall. Surgical transposition of the right ovary and tube with preservation of their vascular supply permitted anastomosis between the left intramural and the right ampullary tubal segments. The ovary was mobilized to restore a proper spatial relationship with the fimbrial extremity of the tube. In the third postoperative cycle, the patient was successful in achieving an intrauterine pregnancy and has now been delivered of a normal live infant. The potential of microsurgical techniques in restoring fertility in the face of unusual pelvic anatomy is reiterated.

Intraoperative management of ureteral injury during operative laparoscopy.

Injury to the ureter from operative laparoscopy is rare. The diagnosis is usually made radiologically, in the postoperative period, when the patient presents with symptoms and signs suggestive of ureteral injury. We report herein a case of ureteral injury resulting from operative laparoscopy for endometriosis. The injury was diagnosed and treated via laparoscopy during the same procedure. The increased utilization of operative laparoscopy to perform more complex procedures increases the potential for operative injury to the ureter. Prior visualization or retroperitoneal dissection of the ureter, in appropriate cases, will help reduce this complication and/or permit a prompt diagnosis in the event of such injury.

Effect of hyaluronic acid on postoperative intraperitoneal adhesion formation and reformation in the rat model.

The local application of 0.25% or 0.4% HA before the induction of a measured laser injury on the rat uterine horn was associated with a significant reduction (P less than 0.05) in postoperative IP adhesions when compared with the group of animals pretreated with the diluent vehicle PBS or received no pretreatment. However, 0.4% HA, when applied in a similar manner, was ineffective in reducing reformation of adhesions after microsurgical adhesiolysis.

The influence of fallopian tube length on fertility in the rabbit.

The correlation between the length of the oviduct and degree of fertility was studied in 16 New Zealand White rabbits subjected to microsurgical resection of differing lengths of fallopian tube involving the isthmus in each case. A highly significant (P less than 0.005) linear correlation was found, suggesting that more than 47% of an oviduct must remain distally before fertility can be anticipated. Absence of the isthmic segment of the fallopian tube was found to be associated with supracervical fetal implantations in the uterus. The importance of the assessment of tubal length as a prelude to reconstructive surgery, especially for reversal of sterilization, is emphasized.

PIP: Evidence suggests that fertility subsequent to tubal reconstruction greatly depends on the length and functional quality of the oviduct. To test the validity of this statement, this study was conducted. 16 sexually mature New Zealand white rabbits were used for the study. Rabbits were used as they have a duplex genital tract to the level of 2 cervices; hence, each animal served as both case and control. The rabbits were preoperatively subjected to alternating 12-hour periods of light and dark and were given standard rabbit diet with liberal water. Aseptic microsurgical techniques were used during the operation. Length of the oviduct was measured with sterile paper tape. Segmented resection and anastomosis were performed on the left oviduct of each rabbit, while the right oviduct was anastomosed after simple transection and served as a control. The ratio of experimental to control pregnancies and the fraction of oviduct remaining distally correlated significantly (P 0.005), indicating that 47% or more of the fallopian tube must remain distally before fertility can be expected to return. In rabbits with a relatively small resected segment of tube (between 4% and 18% of the total tubal length), the uterus revealed normally spaced fetuses; in contrast, rabbits with large resected segment (between 40% and 46% of total length of oviduct) had pregnancies in the proximal supracervical region of the uterus. The findings suggest that oviductal length is a critical factor in achieving subsequent fertility following reversal of sterilization.

Arrested tubal pregnancy.

This communication presents a small series of patients operated on for tubal occlusion resulting from undiagnosed tubal pregnancy. In three of the five patients, tubotubal anastomosis after the resection of the affected tubal segment was performed on a single tube. Two of these three patients achieved viable pregnancies. This fact supports the value of reconstructive tubal microsurgery in arrested tubal pregnancy. The histopathologic findings suggest that chorionic villi are capable of surviving in a recognizable form for at least 15 months after the demise of the tubal pregnancy.