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Newsletter: Summer 2019

Note from the Editor Message from SRS President, Dear SRS Members: Dr. Bala Bhagavath I am very excited to bring to you the Summer 2019 edition of the SRS Dear Colleagues: newsletter. I am excited to share some details of our activities in the past few months, and plenty This newsletter includes two exciting has happened! As usual, the Society for Reproductive Surgeons was very active “surgical innovations“ articles on in the scientific programming of the ASRM 2018 Scientific Congress & Expo. The uterine septum surgical repair and a plenary lecture was given by Dr. Liselotte Mettler and was well-received. The society reflection on uterine transplantation. conducted two Pre-Congress courses, an interactive session, a surgical tutorial, an We also report on the successful SRS- Expert Encounter, a live telesurgery and multiple roundtables. All these were well- SREI Fellows Bootcamp held earlier attended. this year in Houston, TX. Thank you to REI fellow, Dr. Rachel Whynott, The SRS-SREI 2019 Surgical Boot Camp for fellows was successfully conducted in for her thoughtful perspective on Houston in January 2019. Feedback from the attendees was good. A new session, this years’ Fellows Bootcamp. The ‘Meet the Professor’ was very popular, and we plan to allot more time for this feedback from trainees and faculty exercise next year. This year, we are conducting an IRB-approved research to study was very positive. We are excited for the improvement in skills after the boot camp. another great boot camp in January 2020! The Society of Reproductive Surgeons’ manual, Reproductive was released for public consumption. The board members, as well as several other contributors, If you are looking for opportunities have worked hard for the past few years to achieve this. Each chapter has videos for SRS involvement, consider sharing attached to it, and the initial response has been enthusiastic. Please check it out if your challenging or interesting cases you have not done so already! through the SRS discussion forum on the SRS website. Please feel free to Dr. Christianson has worked hard to bring you this edition of the newsletter with reach out to me if you are interested more details on the topics I have mentioned above. In addition, I thank Drs. Pfeifer in contributing to the newsletter! and Flyckt for their contribution to uterine septum management and uterine Thank you to Dr. Rebecca Flyckt transplantation, respectively. Once again, I invite all of you to actively participate for her help with organizing this in the society’s activities, and request that you approach us with any ideas you may newsletter. have to further our common interest in promoting .

The SRS programs for the upcoming Thanks! Congress in Philadelphia are going Bala Bhagavath, M.D. to be amazing, and I look forward to SRS President seeing you all in October.

Best regards, Inside This Issue Mindy S. Christianson, M.D. SRS Surgical Boot Camp 2 Uterus Transplantation: SRS Bootcamp: A Fellow’s The Next Five Years 9 Perspective 3 SRS Website Update 13 Approach to the Septate Uterus: Minimally Invasive Reproductive Tips and Tricks 4 Surgery Fellowship Update 15 SRS Surgical Boot Camp Fourth Annual SRS-SREI Surgical Boot Camp

The Fourth Annual SRS- Ten cadaver stations SREI Surgical Boot Camp for allowed for laparoscopic REI fellows took place on dissection and exercises, January 25th and 26th, 2019 and two cadavers for at the Houston Methodist robotic surgery exercises. Institute for Technology, At the laparoscopic Innovation & Education cadaver stations, trainees (MITIE) in Houston, Texas. practiced dissection in the The successful course was retroperitoneal space and directed by Drs. Steven performed suturing tasks R. Lindheim, Wright State mimicking myometrial University, Boonshoft School closure and cystotomy of , and John repairs. At the robotic Petrozza, Massachusetts surgery cadaver station, General Fertility attendees practiced repair of Center, Harvard School the myometrium and tubal Top: Group photo of fellows and faculty. Middle left: Laparoscopy dry of Medicine. Many other anastomosis. lab. Bottom left: Fellows developing faculty committed their time skills in the cadaver lab. Above: Dr. and energy to make this the The fellows also Richard Reindollar leads the embryo most successful program enthusiastically participated transfer simulator station. yet. The response from in suturing tasks in the attendees was tremendous, dry lab. An element of and the event was very well- competition was introduced attended. by timing participants, which allowed for self-evaluation The station future jobs, academics vs The agenda of the boot and feedback. Further, was very popular, with private sector, and what camp was built upon a a computerized robotic trainees requesting that they should look for when comprehensive mix of simulation station allowed time allotted be increased in they go job hunting. Next lectures and hands-on fellows to hone their skills. the future. year, the plan is to augment activities. The hands-on this session. activities included cadaveric Lastly, the many On a social level, a dissection, laparoscopic hysteroscopic stations networking event allowed All hands on deck, as Drs. suturing in the box trainer, allowed for the practice faculty and fellow trainees Petrozza and Hwang will multiple hysteroscopic of hysteroscopic assembly to interact, allowing each be running the program in training activities, embryo with application of scissors to learn about the other 2020 to make it even better! transfer simulation for each and graspers to remove and the trainees to share Lastly, we thank those attendee in the hands-on bell pepper seed “polyps”, their goals and aspirations. behind the scenes including stations, and insightful resectoscopes to shave One of the favorites added Suzanna Scarbrough, lectures. This resulted potato “fibroids”, and the this year was “Meet the Dani Mosley, Keith Ray, in an enhanced learning hysteroscopic morcellator to Professor” where fellows and all the vendors for experience for trainees and remove model fibroids and could semi-privately chat their support in this most faculty. polyps. and ask questions about successful program!

SRS NEWSLETTER | SUMMER 2019 2 SRS Bootcamp: A Fellow’s Perspective Rachel Whynott, M.D. Fellow, Reproductive and , University of Iowa and

As a first-year REI fellow, I was provided dinner, allowing us more time honored to have the opportunity to to meet with reproductive surgeons participate in the fourth annual SRS- from across the country in a more SREI surgical bootcamp in Houston, informal setting. Texas on January 25th and 26th. It was a fantastic, well-run experience, with In speaking with other fellows who practical learning on cadavers, state-of- were able to attend the bootcamp, it the-art simulators, and with top-notch was apparent that I am not the only surgeons from around the country. one who felt that the bootcamp was Fellows were divided into groups for a great experience, regardless of skill the laboratory sessions in order to level or fellowship surgical volume. have a more personalized experience Below are some comments from co- with faculty members. We spent time fellows: at various hysteroscopy simulators, such as performing “polypectomies” on “The SRS bootcamp is a well-organized, bell pepper seeds, “myomectomies” on unrivaled opportunity for REI fellows potatoes, and even timed how quickly Dr. Rachel Whynott (far right) with Drs. to explore opportunities for surgery in we could assemble a hysteroscope Angela Leung and Vinita Alexander after an our field. It utilizes lectures to introduce blindfolded! I can now say that I can afternoon of working on surgical skills at the the material, and then allows for assemble my hysteroscopy equipment SRS-SREI bootcamp. with my eyes closed. immediate application of the skills in Additional stations included a robotic the lab. So grateful for the leaders in In the cadaver sessions, we were simulator with timed skills games, the our field who devoted their time and assigned multiple tasks, overseen by embryo transfer simulator, and box energies to make it happen.” – J.R. faculty. We laparoscopically dissected trainers for additional laparoscopic the anatomy of the pelvic sidewall, suturing and tying practice. “I think it was a great educational as well as practiced our laparoscopic opportunity that does a very good job suturing with intracorporeal and Interspersed throughout the days were of incorporating both clinically-relevant extracorporeal knot-tying. Dr. Goldberg practical lectures, including anatomy and useful lectures with hands-on even proctored my group as we review, proper port placement, and learning.” – C.B. performed a laparoscopic oophoropexy avoiding and managing injuries. and repaired a cystotomy. We also had We also learned tips for a variety of I believe the bootcamp will continue a station to practice laparoscopic laser procedures, including myomectomy, to inspire REI fellows to maintain ablation on chicken skin and another hysteroscopy, tubal anastomosis, and their surgical skills in order to provide cadaver to practice robotic-assisted management of Müllerian anomalies. comprehensive reproductive care tubal reanastomosis with micro Furthermore, there was a lecture to their patients for years to come. forceps. This was especially helpful for followed by a small group session I know the fellows from the 2019 me, as I performed my first robotic- with faculty to discuss the job search bootcamp are very appreciative of the assisted tubal reanastomosis the and how to navigate the contract experience, and we would like to thank following week. The ability to spend negotiation process. We also had the faculty and sponsors who made time at the console to practice was the opportunity to network with the this opportunity possible. invaluable. faculty outside of the bootcamp at a

SRS NEWSLETTER | SUMMER 2019 3 Innovations

Approach to the Septate Uterus: Tips and Tricks Jacqueline Y. Maher, M.D., REI Fellow, Johns Hopkins University School of Medicine Samantha M. Pfeifer, M.D., Associate Professor, Weill Cornell Medical College

Introduction The septate uterus is the most common Mullerian anomaly, accounting for 35% of all identified uterine anomalies, affecting approximately 2-4% of patients with infertility (1-3). Hysteroscopic septum resection is performed worldwide to improve reproductive outcomes in women who desire fertility. A meta-analysis by Venetis et al. showed that septate uterus was associated with a marginal decrease in pregnancy rate, and an increased rate in miscarriage, preterm delivery, malpresentation, low birth weight, and perinatal mortality (3,4). It has been reported that hysteroscopic removal of a septum was associated with a reduced probability of spontaneous abortion (RR 0.37, 95% CI 0.25 to 0.55) compared with untreated women (4). In a 2017 Cochrane Review of nine studies, three showed a significantly higher pregnancy rate in those that were treated with surgery compared to expectant management, and six studies found no significant difference. They concluded that there is not enough evidence to support the surgical procedure because no randomized control studies have been published (5). It must be noted that the data evaluating outcomes with septate uterus and the effect of treatment are largely from small case studies, with no randomized controlled trials comparing treatment versus no treatment. Currently, the American Society for (ASRM) and the European Society of Human Reproduction and Embryology (ESHRE) guidelines suggest surgical resection of the uterine septum for patients with recurrent miscarriage. However, for patients with infertility, it is less clear, though surgical correction is reasonable to consider after patient counseling (6). The purpose of this article is to review the evaluation and surgical management of septate uterus.

Definition A uterine septum occurs when there is a failure of resorption of tissue after the two paramesonephric (Mullerian) ducts have fused together, typically occurring prior to the 20th embryonic week. Septate uteri have a spectrum of sizes and shapes that range from partial, complete to the internal os, complete to the external os, or complete with extension into the vagina. They vary in thickness and vascularity. To better define a septate uterus and differentiate it from an arcuate or bicornuate uterus, Figure 1: Uterine septum, ASRM PC, Fertil Steril 2016 ASRM has released guidelines with morphometric criteria (Figure 1) (7). Arcuate, which is a normal variant, is defined as an indentation depth from the fundus of < 1cm and an angle of < 90 degrees, whereas septate uteri have an indentation depth from the fundus of > 1.5cm and an angle of < 90 degrees.

Furthermore, ESHRE and the European Society for Gynecologic (ESGE) working group under the name CONUTA (CONgenital Uterine Anomalies) define a septate uterus (Class U2) as one that has an internal indentation >50% of the uterine wall thickness and an external contour straight or with indentation <50%. U2 is further subdivided into U2a for partial septate, in which the septum divides the uterine cavity above the level of the internal cervical os, and a U2b is a complete septum, in which the septum fully divides the uterine cavity to the level of the internal cervical os, but may be associated with a cervical or vaginal septum as well (8). Use of the ESHRE–ESGE classification, compared with the ASRM classification, significantly increases the frequency of septate uterus diagnosis, and may potentially promote more to correct small, potentially clinically-insignificant septae (9).

SRS NEWSLETTER | SUMMER 2019 4 Approach to the Septate Uterus: Tips and Tricks (Continued)

Diagnosis It is important to differentiate a septate uterus from a bicornuate uterus and a uterine didelphys. Historically, laparoscopy and hysteroscopy were used as the gold standard to differentiate these uterine anomalies. However, advancement in imaging modalities now make 3-D transvaginal ultrasound, saline infusion sonogram, and MRI appropriate diagnostic tests as well. Hysterosalpingogram also can be used to define the internal architecture, but it cannot differentiate between a uterine septum and a bicornuate uterus. Figure 2: Partial versus Complete Uterine Septum. ESHRE/ESGE.10

Arcuate

Partial Septum

Complete Septum

Figure 3: 3D Saline ultrasound.9

SRS NEWSLETTER | SUMMER 2019 5 Approach to the Septate Uterus: Tips and Tricks (Continued)

Surgical Management for Partial Uterine Septum Hysteroscopic is preferred to the transabdominal approach, which historically included a Jones or Tompkins Metroplasty. Hysteroscopic approaches include septum incision with micro-scissors, unipolar cautery, bipolar cautery, or laser, or septum resection. Distending media for the uterus include saline, glycine, sorbitol, or mannitol, but is dependent on the incision technique or energy source (7). Benefits to the hysteroscopic approach include lower perioperative morbidity, decreased intra-abdominal adhesion formation, faster recovery, and decrease in pregnancy complications such as uterine rupture since the fundal serosa and superior myometrium are not incised. Thus, a vaginal delivery is not contraindicated after a hysteroscopic metroplasty.

Timing/Pretreatment: Resection of the septum is easier when hysteroscopic visualization is optimal, and the endometrial lining is thin. This can be achieved either by timing surgery during the early follicular phase or pretreating the patient with hormonal regimens. Commonly used pre-treatment medications include continuous combined hormonal contraceptives or progestin only pills, despite lack of data in the literature evaluating these regimens. Danazol or GnRH agonist have been used with equivalent efficacy to thin the endometrium prior to metroplasty (11).

Safety: To increase safety of the procedure and decrease uterine perforation, hysteroscopy can be performed under simultaneous abdominal ultrasound guidance or laparoscopy (12).

An important pearl is to know when to stop, and this includes stopping when: • The tissue changes from being fibrous and avascular to pink, and capillaries are seen. • The septum is visibly gone or the uterine ostia are seen in the same plane bilaterally. • Ultrasound imaging shows the septum is no longer present, or you are approaching the myometrium of the fundus.

In some cases, the hysteroscopic septum resection needs to be done in two stages. As with any hysteroscopic procedure, operative time, fluid deficit, and blood loss may limit the procedure. Additionally, in one series, a residual fundal indentation of greater than 1 cm on follow-up may be an indication for repeating the septoplasty (13). Uterine rupture in subsequent pregnancy following uterine septum incision has been correlated with excessive septal excision, penetration of the myometrium, uterine wall perforation, and excessive use of cautery or laser energy during the initial procedure.

Complete Uterine Septum: For the resection range of the complete septum, surgical management includes two options: incise cervical and uterine septum or preserve cervical septum, incise uterine septum. Resecting the cervical and uterine septum takes less time, but may increase the risk for cervical incompetence in subsequent pregnancy. Resecting the uterine septum starting at the level of the internal os while preserving the cervical septum is more time consuming but can help reduce the potential risk of cervical incompetence (14). Techniques to interrupt and traverse the Figure 4: Courtesy of Jeff Goldberg, CCF 2017 uterine septum above the internal os to allow septal incision are shown here and include use of a curved hemostat or balloon.

SRS NEWSLETTER | SUMMER 2019 6 Approach to the Septate Uterus: Tips and Tricks (Continued) Post-Op Management: Post-op complications, though rare, include uterine perforation, thermal injury, uterine , fluid electrolyte imbalances and intrauterine adhesions. In studies that performed a second look postoperative hysteroscopy, the uterine cavity was reported to be healed by two months (15,16). The risk of intrauterine adhesion formation or Asherman’s syndrome after hysteroscopic uterine septum incision reported a wide range from 5.3-37.5% (17,18). Intrauterine adhesions are thought to develop following endometrial denudation or injury causing the opposing uterine walls to adhere to each other. Candiani et al. showed that two weeks post op, the incised area was depressed with no endometrium, however at eight weeks the uterine cavity was normal (19). Yang et al. performed a hysteroscopic evaluation at one month and found 19% of patients had a normal cavity, but by two months, 100% of patients demonstrated a normal cavity (20).

Options for post-operative adhesion prevention are numerous as listed below, but evidence to support the use of any of these techniques is insufficient (17). • Estrogen: Conjugated equine estrogen 0.625 – 1.25mg daily or twice a day for 2-4 weeks; Estradiol 1-2mg daily or twice a day; Estradiol patch 0.1mg, 1-2 patches twice weekly • Progestins: Given for the last 5-7 days of estrogen • Intrauterine balloon stent: Pediatric foley 8-12 French or Cook uterine balloon catheter. Duration of time is undetermined. • Others: e.g., antibiotics, hyaluronic acid, IUD

Though adjuvant are currently being utilized, recent studies suggest that estrogen administered with a progestin, intrauterine balloon, and IUD placement had no significance in the prevention of intrauterine adhesions after septum resection, nor could it improve the postoperative pregnancy rate (21,22). There are no data evaluating the use of estrogen alone with or without the use of a balloon device to reduce adhesions, which is what many practitioners utilize. Currently, per ASRM Practice Committee guidelines, there is insufficient evidence to recommend for or against adhesion prevention treatment, and additional studies are needed.

Timing to Pregnancy and Outcomes: It is recommended that following hysteroscopic septum incision, pregnancy be delayed for at least two months, based on data in the literature. One study showed that there was no difference in pregnancy and miscarriage rates at <9, 10-16, or >17 weeks post septum treatment (16). Outcomes following hysteroscopic septum incision are favorable. One study found that miscarriage rates decreased from 91.8% to 10.4% following septum incision in 361 patients who had primary infertility of >2 years’ duration, a history of 1–2 spontaneous miscarriages, or recurrent pregnancy loss. Studies have reported an overall pregnancy rate after treatment of 48% (24). After resection of the septum, fetal malpresentation frequency should return to that of the general population.

SRS NEWSLETTER | SUMMER 2019 7 Approach to the Septate Uterus: Tips and Tricks (Continued)

References:

1. Ashton D, Amin HK, Richart RM, Neuwirth RS. The incidence of asymptomatic uterine anomalies in women undergoing transcervical tubal sterilization. and gynecology 1988;72:28-30. 2. Grimbizis GF, Camus M, Tarlatzis BC, Bontis JN, Devroey P. Clinical implications of uterine malformations and hysteroscopic treatment results. Human reproduction update 2001;7:161-74. 3. Chan YY, Jayaprakasan K, Zamora J, Thornton JG, Raine-Fenning N, Coomarasamy A. The prevalence of congenital uterine anomalies in unselected and high-risk populations: a systematic review. Human reproduction update 2011;17:761-71. 4. Venetis CA, Papadopoulos SP, Campo R, Gordts S, Tarlatzis BC, Grimbizis GF. Clinical implications of congenital uterine anomalies: a meta- analysis of comparative studies. Reproductive online 2014;29:665-83. 5. Rikken JF, Kowalik CR, Emanuel MH, et al. Septum resection for women of reproductive age with a septate uterus. The Cochrane database of systematic reviews 2017;1:Cd008576. 6. Checa MA, Bellver J, Bosch E, et al. Hysteroscopic septum resection and reproductive medicine: A SWOT analysis. Reproductive biomedicine online 2018;37:709-15. 7. Johansen G, Lonnerfors C, Falconer H, Persson J. Reproductive and oncologic outcome following robot-assisted laparoscopic radical trachelectomy for early stage cervical cancer. Gynecol Oncol 2016;141:160-5. 8. Grimbizis GF, Di Spiezio Sardo A, Saravelos SH, et al. The Thessaloniki ESHRE/ESGE consensus on diagnosis of female genital anomalies. Gynecological surgery 2016;13:1-16. 9. Ludwin A, Ludwin I. Comparison of the ESHRE-ESGE and ASRM classifications of Mullerian duct anomalies in everyday practice. Hum Reprod 2015;30:569-80. 10. Grimbizis GF, Gordts S, Di Spiezio Sardo A, et al. The ESHRE-ESGE consensus on the classification of female genital tract congenital anomalies. Gynecological surgery 2013;10:199-212. 11. Fedele L, Bianchi S, Gruft L, Bigatti G, Busacca M. Danazol versus a -releasing hormone agonist as preoperative preparation for hysteroscopic metroplasty. Fertil Steril 1996;65:186-8. 12. Coccia ME, Becattini C, Bracco GL, Bargelli G, Scarselli G. Intraoperative ultrasound guidance for operative hysteroscopy. A prospective study. J Reprod Med 2000;45:413-8. 13. Fedele L, Arcaini L, Parazzini F, Vercellini P, Di Nola G. Reproductive prognosis after hysteroscopic metroplasty in 102 women: life-table analysis. Fertil Steril 1993;59:768-72. 14. Wang S, Shi X, Hua X, Gu X, Yang D. Hysteroscopic transcervical resection of uterine septum. JSLS : Journal of the Society of Laparoendoscopic Surgeons 2013;17:517-20. 15. Yang JH, Chen MJ, Chen CD, Chen SU, Ho HN, Yang YS. Optimal waiting period for subsequent fertility treatment after various hysteroscopic surgeries. Fertility and sterility 2013;99:2092-6.e3. 16. Berkkanoglu M, Isikoglu M, Arici F, Ozgur K. What is the best time to perform intracytoplasmic sperm injection/embryo transfer cycle after hysteroscopic surgery for an incomplete uterine septum? Fertil Steril 2008;90:2112-5. 17. Vercellini P, Fedele L, Arcaini L, Rognoni MT, Candiani GB. Value of intrauterine device insertion and estrogen administration after hysteroscopic metroplasty. J Reprod Med 1989;34:447-50. 18. Guida M, Acunzo G, Di Spiezio Sardo A, et al. Effectiveness of auto-crosslinked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic surgery: a prospective, randomized, controlled study. Human reproduction (Oxford, England) 2004;19:1461-4. 19. Candiani GB, Vercellini P, Fedele L, Carinelli SG, Merlo D, Arcaini L. Repair of the uterine cavity after hysteroscopic septal incision. Fertil Steril 1990;54:991-4. 20. Yang J-H, Chen M-J, Chen C-D, Chen S-U, Ho H-N, Yang Y-S. Optimal waiting period for subsequent fertility treatment after various hysteroscopic surgeries. Fertility and Sterility 2013;99:2092-6.e3. 21. Tonguc EA, Var T, Yilmaz N, Batioglu S. Intrauterine device or estrogen treatment after hysteroscopic uterine septum resection. International journal of and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 2010;109:226-9. 22. Yu X, Yuhan L, Dongmei S, Enlan X, Tinchiu L. The incidence of post-operative adhesion following transection of uterine septum: a cohort study comparing three different adjuvant therapies. Eur J Obstet Gynecol Reprod Biol 2016;201:61-4. 23. Saygili-Yilmaz E, Yildiz S, Erman-Akar M, Akyuz G, Yilmaz Z. Reproductive outcome of septate uterus after hysteroscopic metroplasty. Archives of gynecology and obstetrics 2003;268:289-92. 24. Homer HA, Li TC, Cooke ID. The septate uterus: a review of management and reproductive outcome. Fertil Steril 2000;73:1-14.

SRS NEWSLETTER | SUMMER 2019 8 Innovations

Uterus Transplantation: The Next Five Years Elliott Richards, MD; Tommaso Falcone, MD; Andreas Tzakis, MD; Rebecca Flyckt MD Cleveland Lerner College of Medicine Obstetrics/Gynecology and Women’s Health Institute

The field of uterus transplantation has made astounding strides in a brief period of time, both in terms of technical innovation, as well as public perception. In the past five years, we have seen the first baby born in a human trial from a living donor uterus (1); the announcement of multiple uterus transplant trials worldwide (2-5); the use of alternate vessels for venous drainage (6-7); the initial use of laparoscopic and robotic approaches to organ procurement (6,8); and recently, the first baby born from a deceased donor uterus (9). Uterus transplant is no longer a theoretical surgical procedure. To our knowledge, there have been at least 14 babies born from uterus transplant to date, with more anticipated in the coming months. Furthermore, the general public appears to express overall favorable views of uterus transplant, with one recent study reporting 78% of adults in the United States supporting the procedure (10).

Uterus transplant is a burgeoning field of transplant surgery that intersects multiple domains and disciplines. It is the only treatment for absolute uterine factor infertility, which affects an estimated one in 500 women worldwide, either by congenital (e.g., Mullerian agenesis) or acquired (e.g., emergent hysterectomy) causes (11). Other than uterus transplant, absolute uterine factor infertility is an incurable condition. The diagnosis of absolute uterine factor infertility is often devastating. It is a life-framing experience that influences patients’ view of themselves and their acceptance by family, partners, and peers, with feelings of grief and social isolation commonly reported (12). For many of these patients, uterus transplant is viewed as a means to gain control of their reproductive autonomy and to play an active role in their prenatal health and well-being (12).

Like face and hand transplants, uterus transplant is not a life-saving procedure. However, uterus transplant is unique in several important ways. Uterus transplant is an ephemeral transplant, meaning that the organ is transplanted with the explicit intention to remove it at a later time, usually following 1-2 live births (13). Uterus transplant, while not life-saving, is life-propagating (14), denoting the potential of pregnancy following uterus transplant, with health implications for not only the recipient, but also future offspring. Uterus transplant involves a donated organ that may no longer be needed or wanted by a living donor, especially if the donor is post-menopausal; “success” in uterus transplant cannot be ascertained until months to years after the transplant procedure has been performed, since, while graft vascular perfusion, lack of graft rejection, onset of menstruation, and pregnancy implantation are all meaningful clinical milestones and can serve as interim markers of success, liveborn children is the ultimate endpoint determining success for all current reported protocols. Finally, while most other forms of involve only two surgeries (procurement and graft reimplantation), a successful uterus transplant involves a minimum of 3-4 surgeries: procurement, reimplantation, cesarean section, and graft hysterectomy.

Given the complex nature of the surgeries and the longitudinal nature of such an endeavor, it comes as no surprise that the successful creation of a uterus transplant program requires significant expertise, as well as extensive coordination between specialties, including transplant surgery, gynecologic surgery, reproductive endocrinology, psychology, bioethics, and high-risk obstetrics. This spirit of collaboration has been further extended across institutions through the establishment of international societies and inter-institutional partnerships dedicated to uterus transplant (15). Such collaborations have been critical for the development of the field of uterus transplant over the last five years.

The next five years promise to continue at a rapid pace of innovation and progress. Future areas of innovation in living donor surgery include the use of smaller incisions and refined minimally-invasive techniques, with the goal of a completely laparoscopic or robotic procurement without the need for laparotomy. Historically, procurement surgeries have been characterized by long operating times, large incisions, and occasional complications for donors. There is also concern for coercion in living directed (known) donors, who may feel that they cannot decline to provide their uterus to a loved one in need (16).

SRS NEWSLETTER | SUMMER 2019 9 Uterus Transplantation: The Next Five Years (Continued)

For deceased donor programs, innovation is needed in understanding and enhancing graft tissue preservation during cold ischemia. Although this approach eliminates the potential for physical harm to a living donor, there are important limitations in using a deceased donor model, including the fact that appropriate deceased donors are scarce. For 2017, the U.S. Organ Procurement and Transplantation Network reported only 4,000 female deceased organ donors that year, with only 3,400 donors between 18 and 64 years of age. Considering that many of these potential donors may have had hysterectomy or uterine anomalies, the number of potential donors with a suitable uterus would be even lower (17). Improving availability of deceased donor uteri may include increasing radius for procurement or using so-called “increased risk” donors to widen the pool of available organs.

Both living and deceased donor approaches have distinct advantages and disadvantages, and until more data becomes available, neither model is clearly superior. This represents a state of “bioethical equipoise” in the use of living versus deceased donors. It is unclear whether one or the other model will demonstrate better outcomes alongside an acceptable risk/benefit from an ethical standpoint. In addition, recent studies of women (in both uterus transplant trials and in the general public) suggest no strong preference for either model (18). It is possible that a combination of living and deceased donor models could be the future of the field if uterus transplant is ever to become a mainstream treatment.

For the recipient surgery, there is currently great variability in the approach taken by different teams throughout the world, and the optimal strategies of vascular and vaginal anastomosis need to be discussed, determined, and disseminated. For example, vaginal stricture is a common complication for recipients, and gynecologic surgeons have a role in developing improved vaginal anastomosis techniques. In addition, while current protocols restrict uterus transplant trials to healthy patients of low BMI who were biologic females at birth, the field will inevitably expand to allow patients who are not cisgender females or those who have a higher BMI or other pre-existing comorbidities.

Innovation will be needed beyond the screening clinic and operating theater. The long-term outcomes for donors, recipients, offspring, and other family members will be critical to study in transitioning uterus transplant from an experimental into an accepted medical treatment. Continued work is needed to understand the preferences and attitudes of potential and current uterus transplant patients to ensure they continue to have a voice.

It is also critical that investments are made in the basic and translational science. This is needed to allow for possibilities such as uterus tissue bioengineering and uterus xenotransplantation, future technologies which could alleviate many of the concerns for surgical risks and the limited supply of organs (19, 20). Other future surgical innovations may include the concurrent transplantation of the fallopian tubes, which are typically transected to decrease risk of ectopic pregnancy and reduce time to pregnancy using IVF (4), but if included, could allow for spontaneous conception without the need for IVF and embryo transfer.

There are still many unanswered questions in uterus transplant. Despite recent successes, the field is not without its critics, roadblocks, and challenges. Many of the ongoing concerns regarding uterus transplant revolve around access, cost, and safety. These are questions that must be addressed and answered in the coming years alongside future technical innovations. It should be noted that some of the strongest opponents of uterine transplantation are in fact reproductive endocrinologists, due to their experience with gestational carriers. In addressing these concerns, we must consider uterine factor infertility from both a national and international perspective, and recall that throughout most of the world gestational carriers are illegal, highly restricted, or banned completely. Further, research in uterine transplantation is generating insights into early pregnancy implantation, placentation, reproductive , and myriad other domains that extend well beyond our own.

As more children are born through uterus transplant and the technique transitions from experimental science to standard treatment, the question of cost and coverage will become increasingly important. In addition to the surgery itself, there are the costs of and graft removal, which are not insignificant. For administration of uterus transplant to

SRS NEWSLETTER | SUMMER 2019 10 Uterus Transplantation: The Next Five Years (Continued) be just, it should not only be available to those who can afford it. The question of insurance coverage for uterus transplant is part of a larger debate of whether and to what extent infertility treatment should be covered. Present data suggest that there is support for insurance coverage of uterus transplant among the general public, but this may change once the issue enters more public debate. Interestingly, 60% of AAGL and ASRM members responded with support towards uterus transplant as a potential treatment option with absolute uterine factor infertility, however only 35- 40% felt it should be covered by health insurance (21).

The next five years of uterus transplantation promise the same spirit of progress and innovation that characterized the birth of the field. Each phase of this innovative surgical procedure has deepened our understanding of what is required for success Uterine allograft after end to side and the challenges that lay ahead. The initial years of uterus transplant in humans vascular anastomosis of donor demonstrated proof of concept that a surgical treatment for patients with uterine internal iliac artery and vein to factor infertility is possible. In the next 5-10 years, uterine transplant will continue recipient external iliac artery and vein to transition from an experimental possibility to a clinical reality for women with absolute uterine factor infertility. The next phase is certain to be one of refinement, optimization, and continued momentum and innovation.

References:

1. Brännström, M., L. Johannesson, H. Bokström, N. Kvarnström, J. Mölne, P. Dahm-Kähler, A. Enskog, et al. 2015. Livebirth after Uterus Transplantation. Lancet (London, England) 385, no. 9968 (February 14): 607–616. 2. Kuehn, B.M. 2017. US Uterus Transplant Trials Under Way. JAMA 317, no. 10 (March 14): 1005–1007. 3. Flyckt RL, Farrell RM, Perni UC, Tzakis AG, Falcone T. 2016. Deceased Donor Uterine Transplantation: Innovation and Adaptation. Obstet Gynecol. Oct;128(4):837-42 4. Brännström, M. 2018. Current Status and Future Direction of Uterus Transplantation. Current Opinion in Organ Transplantation 23, no. 5 (October): 592–597. 5. Brännström, M., P. Dahm Kähler, R. Greite, J. Mölne, C. Díaz-García, and S.G. Tullius. 2018. Uterus Transplantation: A Rapidly Expanding Field. Transplantation 102, no. 4: 569–577. 6. Wei, L., T. Xue, K.-S. Tao, G. Zhang, G.-Y. Zhao, S.-Q. Yu, L. Cheng, et al. 2017. Modified Human Uterus Transplantation Using Ovarian Veins for Venous Drainage: The First Report of Surgically Successful Robotic-Assisted Uterus Procurement and Follow-up for 12 Months. Fertility and Sterility 108, no. 2: 346-356.e1. 7. Puntambekar, S., S. Puntambekar, M. Telang, P. Kulkarni, S. Date, M. Panse, R. Sathe, et al. 2018. Novel Anastomotic Technique for Uterine Transplant Using Utero-Ovarian Veins for Venous Drainage and Internal Iliac Arteries for Perfusion in Two Laparoscopically Harvested Uteri. Journal of Minimally Invasive Gynecology (December 29). 8. Puntambekar, S., M. Telang, P. Kulkarni, S. Puntambekar, S. Jadhav, M. Panse, R. Sathe, et al. 2018. Laparoscopic-Assisted Uterus Retrieval From Live Organ Donors for Uterine Transplant: Our Experience of Two Patients. Journal of Minimally Invasive Gynecology 25, no. 4 (June): 622–631. 9. Ejzenberg, D., W. Andraus, L.R. Baratelli Carelli Mendes, L. Ducatti, A. Song, R. Tanigawa, V. Rocha-Santos, et al. 2019. Livebirth after Uterus Transplantation from a Deceased Donor in a Recipient with Uterine Infertility. Lancet (London, England) 392, no. 10165: 2697– 2704. 10. Hariton, E., P. Bortoletto, R.H. Goldman, L.V. Farland, E.S. Ginsburg, and A.R. Gargiulo. 2018. A Survey of Public Opinion in the United States Regarding Uterine Transplantation. Journal of Minimally Invasive Gynecology 25, no. 6 (October): 980–985. 11. Flyckt, R., A. Davis, R. Farrell, S. Zimberg, A. Tzakis, and T. Falcone. 2018. Uterine Transplantation: Surgical Innovation in the Treatment of Uterine Factor Infertility. Journal of Obstetrics and Gynaecology Canada: JOGC = Journal d’obstetrique et Gynecologie Du Canada: JOGC 40, no. 1 (January): 86–93. 12. Richards, E.G., P.K. Agatisa, A.C. Davis, R. Flyckt, H. Mabel, T. Falcone, A. Tzakis, and R.M. Farrell. 2019. Framing the Diagnosis and Treatment of Absolute Uterine Factor Infertility: Insights from in-Depth Interviews with Uterus Transplant Trial Participants. AJOB

SRS NEWSLETTER | SUMMER 2019 11 Uterus Transplantation: The Next Five Years (Continued)

Reference, cont.

Empirical Bioethics (March 11): 1–13. 13. Tzakis, A.G. 2013. Nonhuman Primates as Models for Transplantation of the Uterus. Fertility and Sterility 100, no. 1 (July): 61. 14. Olausson, M., L. Johannesson, D. Brattgård, C. Diaz-Garcia, C. Lundmark, K. Groth, J. Marcickiewizc, et al. 2014. Ethics of Uterus Transplantation with Live Donors. Fertility and Sterility 102, no. 1 (July 1): 40–43. 15. Tummers, P., M. Göker, P. Dahm-Kahler, M. Brännström, S.G. Tullius, X. Rogiers, S. Van Laecke, and S. Weyers. 2019. Meeting Report: First State-of-the-Art Meeting on Uterus Transplantation. Transplantation 103, no. 3 (March): 455–458. 16. Williams, N. 2016. Should Deceased Donation Be Morally Preferred in Uterine Transplantation Trials? Bioethics 30, no. 6 (July): 415–424. 17. Shapiro, M.E., and F.R. Ward. 2018. Uterus Transplantation: A Step Too Far. The American Journal of Bioethics: AJOB 18, no. 7: 36–37. 18. Richards, E.G., R. Flyckt, A. Tzakis, and T. Falcone. 2018. Uterus Transplantation: Organ Procurement in a Deceased Donor Model. Fertility and Sterility 110, no. 1: 183. 19. Hellström, M., S. Bandstein, and M. Brännström. 2017. Uterine Tissue Engineering and the Future of Uterus Transplantation. Annals of 45, no. 7 (July): 1718–1730. 20. Brännström, M. 2017. Uterus Transplantation and Beyond. Journal of Materials Science. Materials in Medicine 28, no. 5 (May): 70 21. Bortoletto, P., E. Hariton, L.V. Farland, R.H. Goldman, and A.R. Gargiulo. 2018. Uterine Transplantation: A Survey of Perceptions and Attitudes of American Reproductive Endocrinologists and Gynecologic Surgeons. Journal of Minimally Invasive Gynecology 25, no. 6 (October): 974–979.

Register now at www.asrmcongress.org

SRS NEWSLETTER | SUMMER 2019 12 SRS Website Update J. Preston Parry, M.D., M.P.H After a complete revamping in 2017, the SRS website expansion and development continues. The sowing of seeds that started last year to expand video content has boosted SRS website content. The SRS textbook now has video content through the reprodsurgery.org website, and we will be developing streaming expert opinion sections for both central and favorite topics. We shortly also will be integrating Fertility and Sterility and other video articles into our literature review section.

Beyond continuing standard literature reviews (with particular appreciation to Dr. Stephanie Estes for spearheading a recent series on case volume and outcomes), and increasing activity on the bulletin board (led by Dr. Bala Baghavath and with gratitude to Dr. Anthony Imudia as one of the more frequent posters), we’re also reflecting on growth and engaging the next of others, as well as anonymizing the let me know (including if you have generation of reproductive surgeons. hard work these reviews often require. favorite topics)—we have plenty of Participating in SRS literature reviews articles that deserve greater awareness One of the greatest opportunities for not only allows your colleagues to and expert perspective from SRS this is through the website. When grow directly from your insights, but members! reviewing for a journal, the work often also builds connections and gives credit performed is seen by exceptionally few to contributors. If you are interested in J. Preston Parry, M.D., M.P.H. people, which limits direct influence participating in these reviews, please

The SRS website, www.reprodsurgery.org, now hosts a variety of informative features and sections ONLY available to active SRS New updates on members!

The new update includes a password protected log-in section that reprodsurgery.org! includes the following information:

Feel free to contact the Website Chair, Dr. • SRS Email Discussion List • SRS Literature Reviews John Parry ([email protected]) • SRS Newsletters or Dani Mosley at ASRM (dmosley@asrm. • Surgical Tutorials Uploaded by SRS members org) with any comments or suggestions you may have regarding the SRS website. Please be sure to check the SRS website frequently to see the upcoming and ongoing changes. We value your input and suggestions.

SRS NEWSLETTER | SUMMER 2019 13 Reproductive Surgery: The Society of Reproductive Surgeons’ Manual Available now! Order your copy of Reproductive Surgery: The Society of Reproductive Surgeons’ Manual

The Society of Reproductive Surgeons (SRS) is excited to announce the publication of a handbook on which the Society collaborated, Reproductive Surgery: The Society of Reproductive Surgeons’ Manual. Authored by experts in operative gynecology and , the handbook serves as a key guide to understanding modern surgical procedures for female and .

Edited by SRS members, Drs. Jeffrey M. Goldberg, Ceana H. Nezhat and Jay Sandlow, the manual features step-by-step instructions illustrated with intra- operative photographs and surgical videos designed to increase confidence while providing readers with a comprehensive understanding of the indications, techniques, and outcomes of modern reproductive surgery in order to offer patients surgical options and avoid, or improve, IVF.

Reproductive Surgery: The Society of Reproductive Surgeons’ Manual is available from the publisher, Cambridge University Press. SRS members will receive a 35% discount on the purchase price of the manual by entering the code “SRS19” at checkout.

Benefits of SRS Membership:

• NEW! Secured access to SRS newsletters, literature reviews, surgical videos from SRS members, and the SRS Discussion forum! These benefits are only available to active SRS members. • Involvement in the only society that specifically addresses the issues of pelvic reconstructive surgery in women of reproductive age • Interaction with a national and international group of surgeons who share an interest in reproductive surgery • The opportunity to review research abstracts with a focus on reproductive surgery • Participation in roundtable discussions at ASRM Scientific Congresses • The discussion of novel surgical techniques through video sessions • Participation in surgical hands-on courses at ASRM Scientific Congresses • Access to participate in ASRM Pre-Congress courses on a variety of topics related to the field of reproductive surgery • Participation in collaborative research projects addressing surgical outcomes

SRS NEWSLETTER | SUMMER 2019 14 Minimally Invasive Reproductive Surgery Fellowship Update Jeffrey M. Goldberg, M.D.

SRS has established a one-year • The Advanced Gynecologic Surgery management of pelvic can fellowship program in minimally- Institute, Park Ridge, IL, Program improve IVF results. It is unfortunate invasive reproductive surgery. The Director: Charles Miller, M.D. that many REIs have abandoned enthusiasm of REI fellows at the reproductive surgery or relegated annual SRS Surgical Boot Camp and the Since most REI fellows are not receiving it to general or minimally-invasive favorable results of an online survey adequate training in reproductive gynecologic surgeons. Reproductive of REI fellows demonstrating their surgery, SRS has created this fellowship surgeons have a different skill set desire to obtain surgical training after to provide them with needed skills. It and approach to surgery which could REI fellowship were the impetus to is our intention that graduates of the lead to improved outcomes. REIs who develop this program. It is essentially program will deliver excellent surgical can operate are more “complete” a one-year preceptorship with a high care to their patients, and will then who can offer their patients volume, master reproductive surgeon. teach these skills to their trainees to all of the available treatment options. Our first fellow in the program is Dr. benefit the next generation of patients. Pavan Ananth, M.D., who is currently Hopefully, they also will become Interested applicants for the Minimally- under the training of Dr. Ceana Nezhat. actively involved with SRS to assure the Invasive Reproductive Surgery future of reproductive surgery. Fellowship can find information on The following are programs currently the SRS website at https://www. accepting applications for 2019-2020: There is good evidence-based data reprodsurgery.org/about/fellowship-1. • Nezhat Medical Center, Atlanta, showing that reproductive surgery Interested preceptors also can find GA, Program Director: Ceana is more cost-effective than IVF in information on the website. Nezhat, M.D. many cases, and is often preferred • Camran Nezhat Institute,Palo Alto, by patients as it is more “natural” Jeffrey M. Goldberg, M.D. CA, Program Director: Camran than IVF. Reproductive surgery also is Nezhat, M.D. complimentary to IVF, as the surgical

PRESIDENT IMMEDIATE PAST FELLOWSHIP CHAIR Bala Bhagavath, M.D. PRESIDENT Jeffrey Goldberg M.D. Samantha Pfeifer, M.D. VICE PRESIDENT NEWSLETTER EDITOR Steven R. Lindheim, M.D PAST PRESIDENT Mindy S. Christianson, M.D. Ceana H. Nezhat, M.D SECRETARY/TREASURER REPRESENTATIVES TO John Petrozza, M.D. DOMESTIC MEMBERSHIP ASRM COMMITTEES COMMITTEE Mohamed Bedaiwy, M.D. ASSISTANT SECRETARY/ Ceana H. Nezhat, M.D. Bala Bhagavath, M.D. TREASURER Stephanie Estes, M.D. Kathleen Hwang, M.D. WEBSITE CHAIR Tommaso Falcone, M.D. John Parry, M.D., M.P.H Steven R. Lindheim, M.D. DIRECTOR-AT-LARGE Ceana H. Nezhat, M.D. John Parry, M.D., M.P.H. POSTGRADUATE CHAIR Samantha Pfeifer, M.D. Ceana H. Nezhat, M.D. Elizabeth Pritts, M.D.

SRS NEWSLETTER | SUMMER 2019 15