The current and future state of surgery in reproductive endocrinology.

PURPOSE OF REVIEW: The last decade has witnessed a radical change in the field of reproductive surgery. The increasing success of in-vitro fertilization (IVF) has caused a huge shift in emphasis with many downstream consequences. This review outlines the changes and provides insight into the future of reproductive surgery. RECENT FINDINGS: With compelling evidence that IVF overcomes the detrimental effects of endometriosis on infertility and with two new oral medications available for management of endometriosis, momentum is shifting towards nonsurgical management of endometriosis. There is increasing recognition that except for submucous myomas, other myomas are unlikely to affect fertility and miscarriage. This, in addition to many emerging alternative modalities for management of myomas (oral GnRH antagonists, radiofrequency ablation), is likely to further decrease classic myomectomies but provide alternative, less invasive options. Caesarean scar defects have been recognized as having significant reproductive consequences and surgical management has become the standard of care. Fallopian tubes are now implicated in development of ovarian cancer, and as a result, salpingectomies are being performed in lieu of tubal ligations. Tubal anastomosis will soon become a historical surgery. Division of uterine septum remains controversial, and a clear answer will remain elusive. Uterine transplant is the single most significant advance in reproductive surgery in the past century. SUMMARY: Reproductive surgery is evolving with the times. Although some surgical techniques will become historical, others will become mainstream.

Clinical and Patient Reported Outcomes of Pre- and Postsurgical Treatment of Symptomatic Uterine Leiomyomas: A 12-Month Follow-up Review of TRUST, a Surgical Randomized Clinical Trial Comparing Laparoscopic Radiofrequency Ablation and Myomectomy.

STUDY OBJECTIVE: The objective of this study was to determine the efficacy, safety, and healthcare resource use of laparoscopic radiofrequency ablation (LAP-RFA) compared with myomectomy in patients with symptomatic uterine leiomyomas (ULs). DESIGN: This was a secondary analysis of the original postmarket randomized, multicenter, longitudinal, comparative TRUST (Treatment Results of Uterine Sparing Technologies) United States trial in patients with symptomatic ULs. After the procedure, subjects were followed over a 12-month period. SETTING: Multicenter trial, including hospitals with or without an academic affiliation, surgery centers, and fertility centers performing outpatient procedures for uterine myomas. PARTICIPANTS: A total of 57 patients were randomized to either LAP-RFA (n = 30) or myomectomy (n = 27). INTERVENTIONS: LAP-RFA or myomectomy (laparoscopic or abdominal). MEASUREMENTS AND MAIN RESULTS: The main outcome measures of this study were part of the secondary outcomes of the original TRUST trial. The primary outcome of this study was the reduction of UL symptoms and the improvement in patient-reported outcomes scores over time. Secondary outcomes included postprocedure hospitalization, length of stay, complications, reinterventions, and recovery time. There was a significant improvement in UL symptoms at 3 and 12 months after the procedure within each treatment group, and these improvements were similar between treatment groups. There was a significant reduction in UL symptoms per month between baseline and 12-months after the procedure for both LAP-RFA and myomectomy of 72% and 85%, respectively. A significant improvement was seen in all patient-reported outcomes scores over time for both groups. At 3 and 12 months after the procedure, the percentages of patients who were hospitalized in the LAP-RFA group were 74% and 49% lower than those of patients in the laparoscopic myomectomy group, respectively, with the 3-month difference being statistically significant. The length of hospital stay was significantly shorter in the LAP-RFA group compared with the myomectomy group (8.0 ± 5.7 hours vs 18.8 ± 14.6 hours; p < .05). Doctors recommended taking significantly less time off before returning to work for the patients in the LAP-RFA group compared with those in the myomectomy group (10.3 ± 5.1 days vs 14.5 ± 5.4 days; p < .05). The total number of days until back to normal activity was significantly lower in the LAP-RFA group compared with the myomectomy group (16.3 ± 15.2 days vs 26.5 ± 15.9 days; p < .05). CONCLUSION: The results from this 12-month follow-up study suggest that LAP-RFA is a safe, effective, uterine-sparing alternative to laparoscopic myomectomy in the treatment of ULs. These data points build on previously published studies showing that LAP-RFA has lower healthcare resource use overall, including lower postprocedure hospitalization rate and shorter length of stay. In clinical practice, LAP-RFA is a promising treatment approach to ULs for women.

Prolactin is Expressed in Uterine Leiomyomas and Promotes Signaling and Fibrosis in Myometrial Cells.

Uterine leiomyomas are benign, estrogen-sensitive, fibrotic smooth muscle cell tumors occurring in the uterine myometrium. Leiomyomas are a considerable health burden, with a lifetime prevalence of 80% and limited treatment options. Estrogen and progesterone have positive effects on leiomyoma growth, but little is known about the roles of other hormones. One hormone of interest is prolactin, as it has been described to be present and functional in leiomyomas. The current study investigates prolactin production within leiomyomas and its effects on myometrial cells. RNA isolation and quantitative-PCR of human leiomyoma samples relative to matched adjacent myometrium confirms significant expression of prolactin and dopamine receptor D2, a known regulator of prolactin production and release in the pituitary, with no difference in prolactin receptor expression. Immunohistochemistry confirms increased prolactin in leiomyomas compared to adjacent myometrium and uteri from women without leiomyomas. These results suggest that leiomyomas contain cells that produce prolactin, which may then promote signaling in leiomyoma cells to regulate leiomyoma development/growth. Accordingly, we find that prolactin robustly activates STAT5 and MAPK signaling in rat and human myometrial cell lines. Furthermore, prolactin stimulates expression of myofibroblast markers in rat myometrial cells. Our findings suggest that local prolactin production in leiomyomas may stimulate trans-differentiation of myometrial cells to myofibroblasts, which in turn contributes to the fibrotic nature of leiomyomas.

Crisis Management of Hysteroscopic Surgical Complications in the Office Setting.

IMPORTANCE: As health care providers are increasingly motivated to perform office procedures, there is marginal training and attention related to crisis management (CM). OBJECTIVE: We review the CM in office gynecology and illustrate the value of applying the STOP (stop, think, observe, plan) mental framework to acute management of office hysteroscopy complications. EVIDENCE ACQUISITION: We performed a literature review on crisis management in gynecology. RESULTS: Concepts of team leadership, simulation training, awareness of human error, and panic control are implemented in CM. CONCLUSIONS: Health care providers need to be cognizant of the importance of CM for optimizing patient safety and quality improvement and consider its application on office-based procedures. RELEVANCE: Crisis management has become increasingly relevant in the outpatient setting, seeking to better equip physicians with the skills to manage adverse outcomes while performing office-based procedures.

Specificity of the lactate dehydrogenase isoenzyme index as a preoperative screen for uterine sarcoma before myomectomy.

OBJECTIVE: To evaluate the applicability of the Uterine mass Magna Graecia (UMG) risk index (elevation defined by a lactate dehydrogenase isoenzyme index >29) in women undergoing surgery for benign fibroids and to determine whether other factors were associated with an elevated index. An elevated UMG index has been reported to be associated with an increased risk of uterine sarcoma in Italian women. DESIGN: Retrospective cohort study. SETTING: University fibroid center. PATIENTS: All women presenting from July 1, 2013, through June 30, 2019, with fibroids who had lactate dehydrogenase isoenzymes collected and surgery performed. INTERVENTIONS: Calculation of UMG index. MAIN OUTCOME MEASURE: Applicability of UMG index. RESULTS: Of 272 patients initially identified, 179 met inclusion criteria, 163 with UMG index ≤29 and 16 with UMG index >29. There were no cases of uterine sarcoma. Race, age, and presence of endometriosis, adenomyosis, or degenerating fibroids were not predictors of elevated UMG index. Body mass index (BMI) was positively associated with elevated UMG index. Specificity of UMG index to exclude uterine sarcoma was 91.1% (163/179) and higher in non-obese (BMI<30; 95.1%) than obese women (85.5%). CONCLUSION: A previously reported UMG index cutoff of 29 had a specificity of 91.1% (higher with normal BMI and lower when obese) in our patient population. Although lower than previously reported, the index could be a useful initial method of preoperative screening of women with symptomatic fibroids. Higher BMI appears to be associated with elevated UMG indices, increasing the false-positive rate in obese women.

Longitudinal vaginal septum: a proposed classification and surgical management.

OBJECTIVE: To demonstrate various types of longitudinal vaginal septa (LVS), their classification, and the surgical management of typical and unique morphologic conditions of LVS. DESIGN: Video presentation of clinical appearance and surgical techniques for treatment of LVS. SETTING: University hospital and two private. PATIENT(S): Representative cases from 121 consecutive women treated from 2013 to 2018 with LVS as a part of complex uterovaginal malformations or in isolated forms with [1] typical morphologic configuration of LVS, [2] rarer variants, or [3] specific anatomic restrictions. INTERVENTION(S): Resection of LVS performed as a main surgical procedure in cases with didelphys and bicornuate uterus in symptomatic women and as a part of corrective surgery of complete septate uterus. The three main nonsuturing techniques used were speculoscopy and septum excision using three different electrosurgical modalities; speculoscopy with laparoscopic devices; and vaginoscopy with hysteroscopic instruments. MAIN OUTCOME MEASURE(S): Clinical appearance and suggested classification, feasibility of surgery, and perioperative and anatomic results in a short follow-up period (3 months). RESULT(S): We identified distinct types of longitudinal vaginal septa. Considering clinical appearance, we suggest classification of LVS based on four main features: [2] completeness of vaginal division: partial and complete type; [2] the symmetricity: symmetric and asymmetric position (with dominant left and right side); [3] association with the cervix: merged and isolated forms; and [4] concomitant vaginal openings: normal, and narrow openings: vaginal stenosis and hymen persistent (Fig. 1). Vaginoscopic techniques by hysteroscope were successful in atraumatic treatment of women with substantial anatomic restrictions, and all of the presented techniques can be effectively used for typical LVS. However, vessel-sealing systems allow for bloodless surgery in contrast with other methods. This study was based on previously acquired data during large prospective study approved by the local ethics committee, and written informed consent to participate in the prospective study and permit publishing anonymous data regarding the medical images, videos of procedures, and results was obtained from all patients. CONCLUSION(S): A new classification of longitudinal vaginal septum allows better characterization compared with the currently available classification systems. Different surgical modalities are discussed with their respective advantages and disadvantages. Vaginoscopic incision using resectoscope is a reasonable alternative for women with an intact hymen and vaginal stenosis. The impact of vaginal septum resection on obstetric, reproductive, and sexual outcomes should be assessed in randomized controlled trials and large well-designed studies.

Saline-Air Hysterosalpingo-Contrast Sonography Is Equivalent to the Modified Hysterosalpingogram Following Hysteroscopic Sterilization.

PURPOSE: To estimate the diagnostic efficacy of saline-air hysterosalpingo-contrast sonography (SA-HyCoSy) compared with the modified hysterosalpingogram (mHSG) for confirmation of both coil location and tubal occlusion following hysteroscopic sterilization. METHODS: This study included 19 women who underwent both SA-HyCoSy and mHSG where 1 test was followed by the other. Sensitivity, specificity, and positive and negative predictive values for tubal occlusion against the mHSG were calculated for each fallopian tube by 2 independent interpreters. Interrater reliability was assessed using Cohen κ statistic. Procedure time and pain level by 11-point numeric rating scale of SA-HyCoSy and mHSG were also compared. RESULTS: Thirty-eight fallopian tubes were evaluated. Tubal occlusion was noted in 97.3% of tubes for both interpreters with the mHSG compared with 92.1% and 94.7% with SA-HyCoSy. The positive and negative predictive values for tubal occlusion were 100%/100% and 50%/33%, respectively, with an overall agreement of 97.4% and 95.7%, κ = 0.48, P < 0.01. Saline-air HyCoSy changed interpretation of coil insert location in 50% and 44.7% for each interpreter, being downgraded from optimal to satisfactory in 42.9% (9/21) and 36% (9/25) and upgraded to optimal in 58.8% (10/17) and 61.5% (8/13), respectively. There were no statistically significant differences in procedural time (7.5 vs 9.4 minutes, P > 0.05) or maximum pain scores (2.3 vs 3.1, P > 0.05) for the mHSG compared with SA-HyCoSy. CONCLUSIONS: Our findings revealed a high degree of diagnostic accuracy with SA-HyCoSy for tubal occlusion, although coil location changed in nearly half of cases. Avoidance of radiation and patient convenience/compliance with SA-HyCoSy may outweigh the drawbacks.

Surgical simulation supplements reproductive endocrinology and infertility fellowship training.

OBJECTIVE: To assess if a surgical boot camp improves laparoscopic skill among reproduction endocrinology and infertility (REI) fellows and increases fellow desire to incorporate surgical skills into practice and to examine whether fellowship in vitro fertilization (IVF) volume correlates with surgical efficiency. DESIGN: Prospective evaluation. SETTING: Simulation Center. PATIENTS: Forty REI fellows. INTERVENTIONS: Fellows were timed before and after training in laparoscopic suturing and knot tying and while using virtual simulators. Fellows were surveyed before boot camp on prior experience with IVF and reproductive surgery, and immediately and 1 month after boot camp on their desire to incorporate surgical skills into practice. MAIN OUTCOME MEASURES: Efficiency of laparoscopic suturing and knot tying before and after boot camp; likelihood and persistence of incorporating surgical skills into practice immediately and 1 month after boot camp; and correlation between fellowship IVF volume and fellow surgical efficiency. RESULTS: Fellows experienced significant improvement in laparoscopic suturing (44 sec), intracorporeal knot tying (82 sec), and extracorporeal knot tying (71 sec). Fellows reported being more likely to incorporate operative hysteroscopy (89%), operative laparoscopy (87%), and laparoscopic suturing (84%) into practice immediately following boot camp with no difference 1 month later. Fifty-four percent of fellows reported being more likely to perform robotic surgery after the boot camp, increasing to 70% 1 month later. There were weak correlations between IVF case volume and efficiency in laparoscopic suturing or hysteroscopic polypectomy (Spearman correlation coefficients, -0.14 and -0.03). CONCLUSIONS: An intensive surgical boot camp enhances surgical skill among REI fellows.

Post-Market Safety of Laparoscopic Ultrasound-Guided Radiofrequency Ablation.

BACKGROUND AND OBJECTIVES: Postoperative safety outcomes with laparoscopic intra-abdominal ultrasound-guided radiofrequency ablation, as performed by gynecologic surgeons new to the procedure, were evaluated and compared to the premarket, pivotal study. Post-procedure feedback from surgeons was reported. METHODS: This was a post-market, prospective, single-arm analysis with 4 to 8 weeks follow-up among surgeons (n = 29) with varying levels of laparoscopic surgery experience participating in the ongoing, multinational Treatment Results of Uterine Sparing Technologies randomized clinical trial. Patients were premenopausal adult women (n = 110) desiring uterine-conserving treatment for symptomatic fibroids. During run-in, surgeons received proctored training. Following training, and after performing ≥ 2 procedures, surgeons provided self-assessment and feedback using a standardized form. RESULTS: Surgeons performed 105 procedures with 100 per-protocol patients. The average number of proctored cases per surgeon was 2.48. No acute (≤ 48 hours) serious adverse events occurred (0/101, 0.0%) compared with 2 acute serious adverse events in the premarket study (2/137, 1.46%). Both studies reported 1 near-term (∼30 days) serious adverse event (< 1% for both). In this study, the near-term complication was fever of unknown origin requiring hospitalization related to uterine entry/manipulation. This was categorized as probably device-related; the patient was treated with antibiotics and discharged. Twenty-six surgeons completed the evaluation form; none reported experiencing problems with the procedure. CONCLUSION: Minimally invasive gynecologic surgeons can learn laparoscopic intraabdominal ultrasound-guided radiofrequency ablation and perform it safely (in terms of acute and near-term serious adverse events) after ≥ 2 proctored cases. There were no significant differences in safety outcomes compared to the premarket, pivotal study.

Case Series of Reproductive Outcomes after Laparoscopic Radiofrequency Ablation of Symptomatic Myomas.

STUDY OBJECTIVE: To analyze pregnancy delivery and safety outcomes after patient receipt of percutaneous, laparoscopic intra-abdominal ultrasound-guided radiofrequency ablation (Lap-RFA) for symptomatic uterine myomas. DESIGN: Case series (2010-2017); evidence was obtained from 2 randomized, controlled trials (level I), 6 cohort studies (level II-2), and in commercial settings (level II-3). SETTING: Multiple sites in the United States, Canada, Europe, and Latin America (university hospitals, community hospitals, and stand-alone surgery centers). Commercial cases were United States based and followed US Food and Drug Administration clearance of Lap-RFA. PATIENTS: Premenopausal adult women with symptomatic uterine myoma types 1 through 6. INTERVENTIONS: The Lap-RFA procedure was conducted under general anesthesia with laparoscopic and intra-abdominal ultrasound guidance. MEASUREMENTS AND MAIN RESULTS: Safety unknowns included the safety of a full-term pregnancy for mother and baby, rates of spontaneous abortion, preterm delivery, postpartum hemorrhage, placental abnormalities, intrauterine growth restriction, and vaginal versus cesarean delivery. A total of 28 women (mean age = 35.0 ± 3.4 years) conceived a total of 30 times after Lap-RFA, either as part of a clinical study or in commercial settings. The number of myomas treated per patient ranged from 1 to 7. The diameter of treated myomas ranged from 0.9 to 11.0 cm. Most patients had 1 or 2 myomas, and most myomas were ≤5.5 cm in maximal diameter. The 30 pregnancies resulted in 26 full-term live births (86.7%), all healthy infants, with an equal distribution of vaginal and cesarean deliveries. Four (13.3%) spontaneous abortions occurred. No cases of preterm delivery, uterine rupture, placental abruption, placenta accreta, or intrauterine growth restriction were reported. One event each of placenta previa and postpartum hemorrhage were reported. CONCLUSION: Conception and safe, full-term pregnancy are achievable after Lap-RFA of symptomatic myomas. Additional large, rigorous, multivariate prospective studies that adjust for confounders and report pregnancy outcomes after symptomatic myoma treatment are needed.

Reproductive surgery: decreasing skills and advancing technology-an existential conundrum.

Our article endeavors to be both a review of the recent past and a preview of the future of reproductive surgery. By reflecting on the rate of technological advancement over the past decade, we attempt to predict the trajectory of the next. We also delve into the changing nature and practical challenges of the practice of gynecologic surgery for the reproductive endocrinology and infertility subspecialist. We will explain how technological advances may alter our perception and expectations regarding the indications, timing and extent of surgical intervention in the infertile patient and in the patient seeking preservation of fertility. This review does not aim to be comprehensive, choosing instead to focus on those innovations that hold, in our view, true potential to shape the future of surgical practice. Ours is primarily a technology review. As such, it does not focus on novel surgical techniques, including uterine transplantation and ovarian tissue transplantation.

Creation and Piloting of a Model for Simulating a Minimally Invasive Myomectomy.

INTRODUCTION: In the era of mandatory work hour restrictions for residency programs, the opportunity for mastery of complex surgical skills in the operating room (OR) has been compromised. All the while, gynecologic surgical techniques have continued to expand. Surgical simulation offers an adjuvant modality for helping young surgeons hone their surgical techniques. We sought to design, construct, and pilot a model for simulating a minimally invasive myomectomy procedure for the purpose of resident training. We undertook a preliminary evaluation of the model's validity. METHODS: Gynecologic surgical simulation models were constructed from polyvinyl alcohol poured into 3D-printed injection molds. A total of 12 laparoscopic and 12 robot-assisted simulated myomectomies were performed using the models. Face and content validity were evaluated with post-simulation questionnaires. Construct validity was assessed by comparing procedural metrics (time to completion and estimated blood loss) between residents and attending surgeons. RESULTS: In the post-simulation survey, the majority of attending surgeons agreed the model was realistic (83.3%) and included the critical steps of a myomectomy (87.5%). Most residents agreed they would feel more prepared for a myomectomy if they practiced on the model beforehand (87.5%) and the majority of attending surgeons agreed they would feel comfortable giving a resident more operative autonomy if the resident had previously completed the simulation (71.4%). Procedural metrics were not significantly associated with expertise level. CONCLUSION: We were able to successfully create a model for simulating a minimally invasive myomectomy. Initial simulations using the model were well received by participants. Further development and investigation of the model will be pursued to determine if this is a valid and useful tool for teaching and practicing a minimally invasive myomectomy.

Overcoming the Challenging Cervix: Identification and Techniques to Access the Uterine Cavity.

IMPORTANCE: Cervical stenosis is a challenging clinical entity that requires prompt identification and management in order to avoid iatrogenic injury at the time of endocervical canal cannulation. OBJECTIVE: The aim of this study was to identify cervical stenosis and discuss associated etiologies, risk factors, and review medical and surgical approaches for overcoming cervical stenosis. EVIDENCE ACQUISITION: Computerized searches of MEDLINE and PubMed were conducted using the key words "cervix", "cervical stenosis," "embryo transfer," "hysteroscopy complications," "misoprostol," and "ultrasound." References from identified sources were manually searched to allow for a thorough review. Data from relevant sources were compiled to create this review. RESULTS: Transcervical access to the uterine cavity is frequently required for procedures such as hysteroscopy, dilation and curettage, endometrial biopsy, sonohysterogram, hysterosalpingogram, intrauterine insemination, embryo transfer in those undergoing in vitro fertilization, and insertion of intrauterine devices. These procedures can become complicated when difficult cannulation of the endocervical canal is encountered. Management strategies include preprocedural use of cervical-ripening agents or osmotic dilators, ultrasound guidance, no-touch vaginoscopy, manual dilatation, and hysteroscopic resection of the obstructed endocervical canal. CONCLUSIONS AND RELEVANCE: Cervical stenosis is associated with iatrogenic complications that can result in significant patient morbidity. In patients undergoing in vitro fertilization, difficult embryo transfer is associated with lower pregnancy rates. The clinician should carefully consider the patient's menopausal status, risk factors, and symptoms in order to anticipate difficult navigation of the endocervical canal. Various medical and surgical management strategies, including hysteroscopic resection, can be used to overcome the stenotic cervix.

Virginity-sparing management of blind hemivagina in obstructed hemivagina and ipsilateral renal anomaly syndrome.

OBJECTIVES: To demonstrate the hymen-sparing management of a blind hemivagina in obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome with the use of transrectal ultrasound (TRUS)-guided vaginoscopic septoplasty supported by pre- and postoperative diagnostics with the use of a novel ultrasound technique: 3-dimensional saline-solution infusion contrast sonovaginocervicography (3D-SVC) with virtual speculoscopy. DESIGN: Video presentation of surgical and ultrasound techniques. SETTING: University hospital and two private centers. PATIENT(S): We are demonstrating four cases with blind hemivagina as a component of OHVIRA syndrome and varying level and features of obstruction including: 1) hemihydrocolpos; 2) hemihematocolpos; 3) "old blood" deposits in small hemivagina; and 4) narrow hymenal opening. INTERVENTIONS(S): The patients were diagnosed preoperatively by means of 3D-SVC with the use of TRUS. Surgery was planned according to available data from ultrasound and 3D-SVC, and the place of incision of the vaginal septum and blinded hemivagina with cervix were performed with the use of TRUS guidance. Wide septal incision was performed with the use of a monopolar or bipolar resectoscope with needle Collin electrode, and after incision the occult second of double cervix or part of septate cervix was visualized, and the septum was excised with the use of a loop electrode. In narrow hymenal opening, a small diagnostic sheath was used for wide septal incision. Anatomic results in the vagina were assessed with the use of 3D-SVC 2 months after surgery. MAIN OUTCOME MEASURE(S): Agreement between imaging from preoperative diagnostics with the use of 3D-SVC and intraoperative findings, and anatomic (hymenal integrity, obstruction, status of vagina and cervix) and clinical outcomes (pain). RESULT(S): In these four cases, 3D-SVC accurately recognized the morphology of blind hemivagina, oblique vaginal septa, and double or septate cervix. Successful minimally invasive wide septoplasty with preservation of hymen were performed with the use of hysteroscope and TRUS guidance. Concomitant laparoscopy was performed if endometriosis and hematosalpinx were present. No peri- or late postoperative complications occurred. Patients were discharged within 3 hours or within 12 hours in case of laparoscopy. Anatomic results were optimal (lack of septum) or suboptimal (wide opening) after septum resection and incision, respectively, without recurrence of obstruction according to 3D-SVC. Pain was not noticed 2 months after the primary surgery. CONCLUSION(S): 3D-SVC is a useful and accurate technique in diagnosis, surgery planning, and postoperative assessment in women with blind hemivagina and intact hymen. TRUS-guided vaginoscopic septoplasty is a reasonable alternative to traditional vaginal surgery and allows hymen preservation.