Reproductive outcomes after vaginal repair of isthmocele: A preliminary study and systematic review of the literature.

OBJECTIVE: Although vaginal repair of isthmocele is an effective and safe surgical option, data on reproductive and obstetrical outcomes are lacking. The aim of this study is to evaluate reproductive outcomes of women undergone vaginal repair of isthmocele. We also systematically reviewed the existent literature to offer a general view of available data. STUDY DESIGN: Retrospective analysis of a database prospectively collected between January 2018 and January 2022 at San Raffaele Hospital, Milan, Italy. We included secondary infertile women with ultrasound documented isthmocele who undergone vaginal repair. Post-surgical clinical, reproductive and obstetric outcomes were recorded. An advanced systematic search of the literature up to January 2023 was conducted. RESULTS: 17 women were included. The mean age of the included patients was 37.2 ± 2.7 years. The median of previous caesarian sections was 1 (1-2). One intra-operative complication (5.9 %) was reported (bladder injury, repaired at the time of surgery). At follow up, bleeding was successfully treated in 8 women (8/10; 80 %). Pregnancy was obtained in 7 women (7/17; 41.2 %): the conception was spontaneous in 4 women (4/7; 57.1 %) and trough assisted reproductive technology in 3 patients (3/7; 42.9 %). The mean time from surgery to pregnancy was 10.8 (±6.7) months. One spontaneous abortion was reported (1/7; 14.3 %), while live birth was achieved in 6 pregnancies (6/7; 85.7 %). All deliveries were by caesarian section at a median gestational age of 37.5 (36-38.25) weeks. No obstetrical complications were reported. At the time of caesarean section, no defects on the lower segment were retrieved. Regarding the systematic research, among the 21 studies screened, only 4 articles were included in the review. Pregnancy rate was around 60-70 % with very few obstetrical complications (0.01 %) such as abnormal placentation or preterm birth. CONCLUSIONS: Vaginal repair of isthmocele is a minimally invasive, safe and effective surgical approach in terms of postsurgical residual myometrium tichness. Systematic review to date has found low-quality evidences on the impact of vaginal surgery in the management of secondary infertility and obstetrics outcomes in women with isthmocele.

Minimally invasive surgery for ovarian endometriosis as a mean of improving fertility: Cystectomy vs. CO2 fiber laser ablation what do we know so far?

Minimally invasive surgery emerged in the 1980s as a safe and effective technique which requires smaller incisions and, usually, a shorter hospital stay compared to traditional surgery. Since then, minimally invasive surgery has expanded in many surgical specialties. One of its newest application in gynecology stands in the infertility management of young women with unexplained infertility or suspected endometriosis. In these cases, laparoscopy allows to diagnose and treat the disease aiming to increase at best the chances of spontaneous pregnancy or trough assisted reproductive technology. Nowadays, minimally invasive surgical approach of ovarian endometriosis consists of either laparoscopic cystectomy or ablative techniques such as laparoscopic CO2 fiber laser vaporization. Although cystectomy represents the gold standard according to the latest Cochrane review, some endometriosis experts are worried about its detrimental effect on healthy ovarian parenchyma and suggest preferring a less aggressive approach such as CO2 fiber laser vaporization. The aim of this review is to give an overview of the available evidences about the impact of the two surgical procedures on ovarian reserve markers and pregnancy outcome.

CO2 fiber laser vaporization for endometrioma treatment results in preserved ovarian responsiveness and improved embryo quality in infertile women undergoing ART.

BACKGROUND: Infertile women carrying ovarian endometriomas can be managed either with surgery or by in-vitro fertilization (IVF). The aim of this study was to compare ovarian responsiveness to controlled ovarian stimulation (COS) in assisted reproduction techniques (ART) in infertile women carrying small intact endometriomas and those managed by endometrioma cystectomy or CO2 fiber laser ablation. METHODS: Retrospective case-control study of prospectively collected data including women underwent ART for endometriosis-related infertility. The study group consisted of infertile women undergoing endometriomas CO2 fiber laser vaporization before ART ("ART after laser CO2" group). Controls were infertile women with endometrioma managed by cystectomy before ART ("ART after cystectomy" group) and infertile women with small endometriomas undergoing ART as first approach ("ART only" group). RESULTS: Of the 86 included patients, 27 (31.4%) belonged to "ART after laser CO2" group, 37 (43%) to "ART after cystectomy" group and 22 (25.6%) to "ART only" group. Surgical groups had larger endometriomas than patients referred to "ART only" group. No between-groups differences were observed in terms of COS protocol, gonadotropins starting and total doses and length of COS. While women belonged to "ART after cystectomy" group had fewer recruited follicles (P=0.014), oocytes (P=0.042), MII oocytes (P=0.042) and formed embryos (P=0.004) compared to women of "ART only" group, no significant differences were found between patients of "ART only" group "ART after laser CO2" group. A greater number of good-quality embryos were observed in surgical groups. No between-groups differences were found in clinical pregnancy rates. CONCLUSIONS: Our results demonstrate encouraging findings on IVF/ICSI outcomes after laser CO2 endometrioma ablation in terms of both quantity and quality of developed embryos.

Fertility Sparing Procedure using Carbon Dioxide Fiber Laser Vaporization of Ovarian Endometrioma.

The surgical management of endometrioma is still a matter of debate. Cystectomy, which is recognized as the standard technique, seems to be associated with a potential reduction in the ovarian reserve due to the inadvertent removal and thermal damage of healthy ovarian tissue. New ablative techniques with reduced tissue penetration depth and less thermal spread to the surrounding parenchyma may represent a viable alternative to cystectomy. For these reasons, the aim of this manuscript is to demonstrate the ablation of the endometrioma capsule using a CO2 fiber laser technique and discuss the clinical outcomes. Once the cyst has been drained and washed, a biopsy is taken. After cyst eversion, vaporization of the inner surface of the cyst is performed using a CO2 fiber laser. The technique is simple and reproducible as even young surgeons without any surgical experience were more confident in performing laser CO2 vaporization instead of cystectomy. The positive effects of CO2 technology are reported in a randomized controlled trial, where the postoperative changes in the antral follicular count (AFC) and antimullerian hormone (AMH) levels were compared between patients who had their endometrioma excised (cystectomy) and those who had undergone endometrioma vaporization with CO2 laser. The patients treated with CO2 laser showed significantly increased AFC without a reduction in serum AMH levels as compared to the cystectomy group, in which both parameters were significantly reduced. The postoperative pregnancy rate was also assessed, and comparable pregnancy rates were found after both treatments. On the contrary, patients treated with the CO2 fiber laser technique had more favorable in-vitro fertilization (IVF) outcomes compared to cystectomy. In conclusion, the CO2 fiber laser technique may represent a viable alternative to cystectomy in the surgical treatment of endometrioma in terms of ovarian preservation, pregnancy rates, and IVF outcomes. Moreover, it has the advantage of being independent of the surgeon's skills and personal experience.

A Systematic Review of Atypical Endometriosis-Associated Biomarkers.

Ovarian endometriosis may increase the risk of malignancy. Several studies have suggested atypical endometriosis as the direct precursor of endometriosis-associated ovarian cancer. We performed an advanced, systematic search of the online medical databases PubMed and Medline. The search revealed n = 40 studies eligible for inclusion in this systematic review. Of these, n = 39 were finally included. The results from included studies are characterized by high heterogeneity, but some consistency has been found for altered expression in phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway, ARID1a, estrogen and progesterone receptors, transcriptional, nuclear, and growth factors in atypical endometriosis. Although many targets have been proposed as biomarkers for the presence of atypical endometriosis, none of them has such strong evidence to justify their systematic use in clinical practice, and they all need expensive molecular analyses. Further well-designed studies are needed to validate the evidence on available biomarkers and to investigate novel serum markers for atypical endometriosis.

Fertility Outcome after CO2 Laser Vaporization versus Cystectomy in Women with Ovarian Endometrioma: A Comparative Study.

STUDY OBJECTIVE: To assess the postoperative likelihood of conception in patients with endometriomas managed by either CO2 laser vaporization or cystectomy. DESIGN: A retrospective study with prospective recording of data. SETTING: University hospital. PATIENTS: One hundred and forty-two patients with symptomatic endometriomas. INTERVENTIONS: Patients underwent a standardized laparoscopic stripping technique (Group 1) or cyst vaporization with CO2 fiber laser (Group 2). Patients wishing to become pregnant were allowed to attempt a spontaneous conception after surgery. If spontaneous conception failed, patients were referred for in vitro fertilization (IVF). MEASUREMENTS AND MAIN RESULTS: The primary objective was to compare pregnancy rates between the 2 groups. The secondary objective was the identification of independent predictors of pregnancy. Thirty-nine women in Group 1 (53.4%) and 39 women in Group 2 (56.5%) desired to conceive after surgery. Three patients (7.7%) in Group 1 became pregnant following donor-IVF and were excluded. Pregnancies were recorded in 72.2% of patients treated with cystectomy and in 74.3% of those managed with CO2 fiber laser (p = .83). Twenty patients (55.6%) in Group 1 and 14 patients (35.9%) in Group 2 conceived spontaneously (p = .08). Among patients who failed spontaneous conception, 21 patients (28%) achieved pregnancy through IVF (Group 1: n = 6, 16.7%; Group 2: n = 15, 38.5%; p = .08). Twenty patients (26.7%) never became pregnant. Age at the time of surgery (odds ratio (OR) = 0.86; 95% Confidence intervals (CI): 0.78-0.96, p = .002) and duration of infertility (OR=0.80; 95% CI: 0.69-0.92, p = .006) were identified as independent indicators for pregnancy. CONCLUSION: CO2 laser-treated endometrioma is associated with pregnancy rates equal to those observed after cystectomy and favorable IVF outcomes. The one step CO2 fiber laser technique may represent a viable alternative to cystectomy.

Ovarian responsiveness in assisted reproductive technology after CO2 fiber laser vaporization for endometrioma treatment: preliminary data.

BACKGROUND: Data about endometrioma ablation using energies with little thermal spread reported good results in terms of ovarian reserve and postoperative pregnancy rates. The aim of the present study was to assess the impact of one step CO2 fiber laser vaporization for endometrioma on subsequent controlled ovarian stimulation. METHODS: This prospective observational cohort study included a consecutive series of infertile patients who have undergone CO2 fibre laser vaporization for endometrioma treatment. The primary endpoint was to assess the number of follicles per ovary growing during controlled ovarian stimulation. The secondary endpoints included the number of oocytes retrieved, the total number of embryos obtained and the cumulative clinical pregnancy rate per patient treated. RESULTS: Twenty-six patients underwent assisted reproductive technology after surgery for endometriosis-related infertility. In unilateral operated ovaries at the end of controlled ovarian stimulation no significant differences emerged from comparison of total recruited follicles in the operated ovary and in the contralateral ovary (P=0.55). If considering only bilateral endometriomas, the number of recruited follicles at the end of controlled ovarian stimulation was similar in both operated ovaries (P=0.79). The number of cumulative clinical pregnancies was 15 (57.7%; 95% CI: 38.5-76.9%). When comparing women aged ≤35 years to those aged >35 years, controlled ovarian stimulation outcomes were significantly higher in the younger patients. Age at the time of assisted reproductive technology was the only independent predictor for follicular growth during ovarian hyperstimulation (95% CI: -1.27 to -0.116, P=0.027). CONCLUSIONS: CO2 laser-treated endometrioma is associated with favorable reproductive assisted reproductive technology outcomes.

Oocyte Retrieval during Laparoscopic Vaginoplasty to Reduce Invasiveness in the Treatment of Mayer-Rokitansky-Küster-Hauser Syndrome.

STUDY OBJECTIVE: To evaluate the treatment of patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome with a combination of oocyte retrieval and surgical vaginoplasty in a single laparoscopic procedure. DESIGN: A case series. SETTING: The study was conducted at 2 tertiary referral facilities for MRKH syndrome in Milan, Italy, between July 2017 and September 2018. PATIENTS: Eleven patients presented with MRKH and required surgical vaginoplasty while expressing a desire for future fertility. INTERVENTIONS: Two experienced surgeons and an expert in assisted reproductive technology performed concomitant vaginoplasty according to the modified technique of Davydov and laparoscopic oocyte retrieval for gamete cryopreservation. MEASUREMENTS AND MAIN RESULTS: Before the procedure, patients underwent extensive counseling and gave written consent. At the start of surgery, 10.4 ± 4.4 (mean ± standard deviation [SD]) oocytes were retrieved laparoscopically, and 8.8 ± 3.1 (SD) mean mature oocytes were cryopreserved. After oocyte retrieval, the steps of the modified Davydov technique were followed. The total operative time was 116 ± 16 minutes (mean ± SD), and no intraoperative/postoperative complications were observed. CONCLUSION: This is the first report of combined oocyte retrieval and vaginoplasty for patients with MRKH syndrome. The approach was found to be feasible in patients with a desire for future fertility. It is our belief that physicians treating patients with MRKH should refer patients to centers with expertise in both vaginoplasty and assisted reproductive technology.

Recurrence Rate after "One-Step" CO2 Fiber Laser Vaporization versus Cystectomy for Ovarian Endometrioma: A 3-Year Follow-up Study.

STUDY OBJECTIVE: To assess postoperative recurrence rates in patients with endometriomas managed by either "one-step" CO2 fiber laser vaporization or cystectomy. DESIGN: Retrospective study with prospective recording of data. SETTING: University hospital. PATIENTS: One hundred twenty-five patients with symptomatic endometriomas. INTERVENTIONS: Patients underwent a standardized laparoscopic stripping technique (group 1) or cyst vaporization with CO2 fiber laser (group 2). After surgery, patients were incorporated in a prolonged surveillance program with periodic clinical follow-up to check for recurrence of the cyst and/or recurrence of symptoms. Endometrioma recurrence was defined as an ovarian cyst (>10 mm) with a typical aspect arising on the operated ovary identified by transvaginal ultrasound. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the comparison of recurrence rates between the 2 groups. The secondary endpoint was the evaluation of endometriosis-related pain recurrence in the 2 groups. Other endpoints selected for analysis included the identification of risk factors for the recurrence of endometrioma and of endometriosis-related symptoms. The mean follow-up was 29 ± 13 months (range, 13-49). Recurrence of ovarian endometriosis was recorded in 6.3% of patients (n = 4) treated with cystectomy and in 4.9% of patients (n = 3) managed with CO2 fiber laser (p = .74). Recurrence of endometriosis-related pain was observed in 5 patients (7.8%) in group 1 and in 6 patients (9.8%) in group 2 (p = .67). Mean endometrioma diameter > 5 cm at the time of surgery was identified as the only independent poor prognostic indicator for cyst recurrence (p = .008; odds ratio [OR], 2.21; 95% confidence interval [CI], 1.19-3.32). Moreover, the presence of deep endometriosis at surgery (p = .032; OR, 4.60; 95% CI, 1.14-18.57) and discontinuation of hormonal treatment (p = .015; OR, 3.18; 95% CI, 1.25-8.06) were independent poor prognostic indicators for pain recurrence. CONCLUSION: This study suggests that one-step CO2 fiber laser vaporization may be effective for endometrioma treatment because it is associated with recurrence rates comparable with those occurring after cystectomy, with the advantage of being an ovarian tissue-sparing technique.

Mini-invasive transvaginal repair of isthmocele: a video case report.

OBJECTIVES: To describe our technique for transvaginal treatment of isthmocele. DESIGN: Surgical video article. Local Institutional Review Board approval for the video reproduction was obtained. SETTING: A scientific institute. PATIENT(S): A 26-year-old patient complaining of abnormal uterine bleeding and pelvic pain was referred to our gynecological clinic for secondary infertility. At transvaginal ultrasound examination, a cesarean scar defect of 22 × 11 mm was identified, with a residual myometrial thickness over the defect of 2 mm. INTERVENTION(S): Isthmocele excision and myometrial repair was performed transvaginal, under regional anesthesia. Before surgery, a hysteroscopy was performed to identify the dehiscence of the cesarean scar on the anterior wall of the uterus and to confirm the presence of the isthmocele and its distance from the external os. Then an incision was made at the anterior cervicovaginal junction and the bladder was dissected away until the anterior peritoneal reflection was identified. Hysteroscopic guidance by transillumination was used to identify the exact position and the limits of the isthmocele. The fibrotic tissue was then removed, and the myometrial defect was closed with interrupted sutures by using 2-0 Vicryl, engulfing the myometrial fibers that would tend to slide laterally. The vaginal mucosa was then sutured with interrupted Vicryl 2-0 sutures. At the end of the procedure, a hysteroscopy was performed to visualize the correction of the defect and to prove the continuity of the cervical canal with the uterine cavity. MAIN OUTCOME MEASURES(S): Repair of isthmocele and relief of symptoms. RESULT(S): The postoperative course was uneventful, and the patient was discharged the day after surgery. At 1-month follow-up pelvic ultrasound showed complete anatomic repair of the uterine defect. The patient was asymptomatic with no more postmenstrual bleeding. She is satisfied with the treatment and is still trying for pregnancy. CONCLUSION(S): Symptomatic isthmocele can be treated surgically via a hysteroscopic, laparoscopic, or vaginal approach, depending on the clinical findings and the skill set and comfort level of the surgeon. Unfortunately, there is no consensus about the ideal surgical approach. The hysteroscopic approach has been demonstrated to be effective for the treatment of abnormal uterine bleeding; however, it does not strengthen the uterine wall and it has a risk of bladder injury. The laparoscopic approach provides good anatomic results, but it requires general anesthesia and may be associated with bladder injury. The transvaginal approach appears to be a feasible, effective, and safe modality to repair the uterine defect and to restore the original thickness of the myometrium. It is a minimally invasive, scarless, and low-cost procedure. It ensures quick recovery and a relatively pain-free postoperative course with early return to normal function.

Flexible CO2 laser fiber: first look at the learning curve required in gynecological laparoscopy training.

BACKGROUND: The advent of flexible CO2 laser fiber to gynecology arena might represent a turning point in the use of laser energy on a large-scale basis in gynecological surgery. However, there might be some concerns regarding the degree of surgical skills required to use the flexible system. The purpose of our study is to evaluate whether flexible CO2 laser fiber is technically accessible. METHODS: Fourteen residents in Obstetrics and Gynecology without surgical experience attending laparoscopic box training with both flexible CO2 laser fiber and traditional line-of-sight CO2 laser using Lumenis AcuPulse Duo CO2 laser (Lumenis, Yokne'am Illit, Israel) were prospectively enrolled. Participants were tested at sequential time points on specific surgical tasks and results obtained with the flexible CO2 laser fiber and the traditional line-of-sight CO2 laser were compared. Results were compared by means of paired t-test and a two-tailed P value <0.05 was considered significant. RESULTS: Mean grading at the beginning of training were similar between flexible fiber and line-of-sight CO2 laser. At the end of training, significant improvement in surgical skills was obtained for both techniques, with a statistically significant higher grading for flexible fiber CO2 laser compared to line-of-sight CO2 laser. CONCLUSIONS: Our study found that residents without surgical experience show better skills with the flexible CO2 laser fiber delivery system compared to the standard line-of-sight CO2 laser system after a two-month training period with gynecological laparoscopic box. According to our results, flexible CO2 laser fiber delivery system is technically accessible and holds a potential in gynecological surgery.

External validation of the endometriosis fertility index (EFI) for predicting spontaneous pregnancy after surgery: further considerations on its validity.

BACKGROUND/AIMS: The revised American Society for Reproductive Medicine classification of endometriosis has a limited predictive value for pregnancy after surgery. A tool for predicting spontaneous pregnancy or pregnancy following assisted reproduction technology (ART) represents a clinical need. This study aimed to (i) provide an external validation of the EFI score in predicting pregnancy in infertile Italian endometriosis women; (ii) evaluate the predictive value of EFI score on ART outcome for patients who previously attempted to spontaneously conceive after surgery. METHODS: In 104 women with endometriosis, EFI score was calculated based on a prospective database data. Cumulative pregnancy rates curves were calculated using Kaplan-Meier (K-M) product limit estimate and log-rank test was used to evaluate differences between EFI groups. A receiver operating characteristic (ROC) curve was plotted for EFI as a predictor of ART outcome. RESULTS: Differences in time to non-ART pregnancy for the six EFI groups were statistically significant (log-rank, p = 1.4 × 10(-4)). The area under the curve (AUC) for EFI as ART outcome predictor was 0.75 (95% CI 0.61-0.89, p = 6.2 × 10(-3)), while the best cut-point for pregnancy was 5.5. CONCLUSION: The EFI score is a reliable scoring system to predict non-ART and ART pregnancy outcome after surgery for endometriosis.

Continuous low-dose oral contraceptive in the treatment of colorectal endometriosis evaluated by rectal endoscopic ultrasonography.

OBJECTIVE: Limited attention has been focused on the medical treatment of bowel endometriosis. This study evaluates the efficacy of administration of a continuous low-dose oral contraceptive in treating pain and other symptoms associated with colorectal endometriotic nodules, as evaluated by rectal endoscopic ultrasonography. DESIGN: Prospective observational study. SETTING: Academic Department of San Raffaele Scientific Institute, Obstetrics and Gynecology Unit. POPULATION: Symptomatic women of reproductive age (n=26) with colorectal nodules infiltrating at least the bowel muscularis propria and without a stenosis >50%. In 31% of the patients, endoscopic ultrasonography permitted diagnosis of nodules located more than 10 cm from the anal rim. METHODS: Patients received a continuous low-dose oral contraceptive containing 15 µg ethinylestradiol and 60 µg gestodene for 12 months. Subjective symptoms were prospectively evaluated, and nodule volumes were monitored using endoscopic ultrasonography. MAIN OUTCOME MEASURES: Nodule measurements were performed at baseline and after 12 months of treatment. Symptoms at the start and after 12 months were evaluated. RESULTS: A significant improvement in the intensity of all the considered symptoms (dysmenorrhea, non-menstrual pelvic pain, deep dyspareunia and painful defecation) was seen when evaluated by a visual analog scale. A reduction in terms of both diameter (mean reduction 26%) and volume of the nodules (mean reduction 62%) was observed after a 12 month period. CONCLUSIONS: A continuous low-dose oral contraceptive therapy may reduce bowel endometriosis-associated symptoms. In addition, this therapy induces a significant volumetric reduction of colorectal plaques when evaluated by endoscopic ultrasonography.

High rate of endometriosis recurrence in young women.

OBJECTIVE: To evaluate rate and determinants of long-term recurrence of endometriosis in a population of young women. DESIGN: Retrospective cohort study. SETTING: University tertiary care referral center for women with benign gynecologic diseases. PARTICIPANTS: Young women undergoing first-line conservative surgery for endometriosis were eligible for the study. Data on age at surgery, disease stage, anatomical characteristics of endometriotic lesions, and endometriosis-related symptoms were collected. After diagnosis, patients were treated according to the standard care of the center. The protocol required all women to be followed up 1 month after surgery, and every 6 months afterward, with an interview to investigate persistence of symptoms, a clinical examination, and an ultrasound pelvic assessment. RESULTS: Fifty-seven women aged ≤ 21 (mean age at diagnosis ± SD: 19.0 ± 1.1 years) entered the study. During a 5-year follow-up, 32 (56%, 95% confidence interval [CI]: 43%-68%) recurrences of endometriosis were diagnosed. A second laparoscopy to treat the recurrence was performed in 11 (34%) cases and confirmed the presence of the disease in all of them. In the remaining 21 (66%) cases, the recurrence was based on the reappearance of the symptoms or clinical or sonographic findings. The recurrence rate increased constantly with time from first surgery. No association emerged between recurrence rate and endometriosis-related symptoms, site/stage of the disease, type of surgery, and post-surgical medical treatment. CONCLUSIONS: The recurrence rate of endometriosis in young women appears higher than in older women. Since no determinants for recurrence have been detected among the factors examined, a profile of women at increased risk cannot be drawn.