Cancer continues to remain a leading cause of death in the United States and can have life-changing impacts. According to the National Cancer Institute statistics, about 10% of new cases of invasive cancer are diagnosed in women of reproductive age . Although patient survival has shown a significant improvement over the last decade, many cancer treatment options including chemotherapy and radiation therapy can negatively affect a women’s reproductive health and her ability to bear children. Therefore, there is considerable interest in fertility preservation options for women of reproductive age who are planning cancer treatments. However, having fully informative conversations on fertility preservation can often be challenging for clinicians, especially in the highly emotional context of a new cancer diagnosis. For this reason and others, physician–patient discussions of fertility preservation are still far from universal. Furthermore, for young women who do receive fertility preservation counseling, only a few actually undergo fertility preservation procedures due to social, financial, cultural, or technical limitations . Providing answers and increasing the availability of fertility preservation options to women who seek these services in the setting of a cancer diagnosis would remain a challenge for health-care providers in the coming years.
The majority of cancer treatments including chemotherapy (specifically the use of alkylating agents such as cyclophosphamide), pelvic radiation, surgery, bone marrow transplantation, or a combination of these treatments can have a harmful impact on a woman’s reproductive capacity, ovarian reserve, and uterine function. Given these documented negative effects on a woman’s reproductive system, ovarian function, and subsequently her quality of life, fertility preservation options appropriate to each of these settings should be discussed. Hematologic cancers and breast cancer are the most frequent indications for fertility preservation .
There are currently three major fertility preservation strategies that can be used either singly or in combination. These include medical options, surgical options, and assisted reproductive technologies (including oocyte and embryo cryopreservation as the standard options) available to preserve the fertility of young women with cancer. In this chapter, we will focus on three fertility-preserving surgical techniques. Procedures to be discussed include ovarian transposition, ovarian tissue harvesting for cryopreservation, and ovarian autotransplantation.
10.2 Ovarian Transposition
Pelvic irradiation is indicated for the treatment of some malignancies including Hodgkin’s lymphoma and genitourinary cancers; it is known that this type of radiation can result in ovarian follicular damage and subsequent loss of ovarian function. Radiation doses as low as 2 Gy can result in the loss of half of human oocytes . Ovarian transposition is a surgical approach that has been developed to minimize radiation damage to the ovaries without having to remove them. This procedure can be done laparoscopically or via laparotomy. The goal of ovarian transposition is to reposition the ovaries outside of the radiation field. The ovaries can be transposed to a variety of different locations, and transpositions have been described anywhere from the base of the round ligament to the level of the kidneys. The exact location for ovarian transposition depends on patient’s anatomy and the planned radiation field. Patients are usually marked on the skin for the radiation field. When deciding the level of transposition, the amount of radiation outside the field should be calculated. The ovaries are commonly transposed to the high lateral abdominal wall above the pelvic brim and outside of the radiation field cases of mid-pelvic irradiation such as what is recommended for vaginal, rectal, and cervical cancers. Another site for ovarian transposition is medially behind the uterus. This is the preferred location in the cases of planned abdominal radiation. The ovaries can also be transposed to distant locations [5–13]. Ovarian transposition can be performed laparoscopically or via laparotomy, as discussed in the following section.
10.3 Ovarian Transposition via Laparotomy
Ovarian transposition via laparotomy often requires a large abdominal incision and can be performed at the same time as a primary staging surgery or as a separate procedure . Transposition via laparotomy has been reported to be associated with a successful preservation of ovarian function in approximately 83% of patients undergoing pelvic radiation . Transposing the ovaries by laparotomy is associated with a longer hospital stay and postoperative recovery, as well as increased risks of adhesion formation and post-op intestinal obstruction. Furthermore, initiation of therapies is often delayed. For this reason, unless performed as part of a concomitant staging surgery, most centers now perform ovarian transposition via a minimally invasive approach.
10.4 Laparoscopic Ovarian Transposition
Laparoscopic ovarian transposition is accompanied by decreased postoperative discomfort due to smaller incisions, shorter hospital stay, more rapid recovery, and return to planned radiotherapy . Laparoscopic transposition is therefore the preferred and more effective method for ovarian transposition and has been described using conventional laparoscopy, single-port methods, or robotic surgery. Laparoscopic ovarian suspension has been reported to have as high as 88.6% chance of successful ovarian function preservation . As stated earlier, the anatomic positioning of the ovary with transposition depends on the type of radiation planned. Posterior-medial ovarian transposition is accomplished by mobilization of the ovary and fixation of the ovary to the uterosacral ligament. The uterus will then shield the transposed ovaries. Lateral ovarian transposition may be more effective in ovarian protection and is our preferred method for ovarian transposition.
One main consideration is whether to transpose the fallopian tube to the ovary. Various reports have described different strategies to approach the fallopian tubes at the time of oophoropexy. One advantage to leaving the fallopian tube intact is the option of having to avoid the cost of having to undergo in vitro fertilization (IVF) to achieve pregnancy, which may not be available to some patients due to limited financial resources. To enable this, we prefer to keep the tube attached and dissect the tube off the vascular pedicle that binds it to the ovary-mesosalpinx. In the following section we will describe our technique for laparoscopic lateral ovarian transposition.
10.5 Laparoscopic Lateral Ovarian Transposition: Surgical Technique
After induction of anesthesia, the patient is placed in standard dorsal lithotomy position. A Foley catheter is placed into the urinary bladder. A uterine manipulator is also inserted.
Four laparoscopic trocars are placed to facilitate laparoscopic intracorporeal suturing and knot tying. Initially, a small 5 mm infraumbilical skin incision is made using a scalpel. After insertion of the 5 mm optical trocar to introduce the laparoscope and obtaining adequate pneumoperitoneum, three additional 5 mm laparoscopic trocars will be introduced under direct visualization: two on the side of the primary surgeon and one on the other side. In this example, we will place two trocars on the left side. The right trocar will be placed at the level of the iliac crest to serve as a landmark for transposition. After performing a thorough survey of the abdominal and pelvic cavities with attention to metastatic implants on the liver, diaphragm, and omentum, the peritoneum is elevated laterally above the exterior landmark of the iliac crest on the abdominal sidewall and incised with scissors (Figure 10.1). Next, the ovary is grasped and the utero-ovarian ligament is electrocoagulated and transected (Figure 10.2). In order to be able to extend and fix the ovary as high and as lateral as possible, it has to be detached from the uterus by taking the utero-ovarian ligament. The blood supply to the ovary is then isolated by incising the peritoneum medially and laterally to the infundibulopelvic ligament. The infundibulopelvic ligament is isolated and mobilized away from the ureter. The peritoneal incisions are extended along the length of the ovarian vessels until the ovary is reached (Figure 10.3). Next, the ovary is separated from the fallopian tube (Figure 10.4). When the ovary is completely mobilized, a blunt grasper is used to create a tunnel in the retroperitoneum from the initial defect above the pelvic brim to the secondary defect in the area of the infundibulopelvic ligament (Figure 10.5). The ovary is gently grasped and guided through the retroperitoneal channel out through the superior defect in the peritoneum (Figure 10.6). In so doing, the ovary will now be positioned above the iliac crest with ovarian vessels coursing superiorly in the retroperitoneal space. It will therefore be mobilized laterally and cephalad to the level of the anterior-superior iliac spines and lateral to the psoas muscles. Retroperitoneal tunneling of the ovary is a unique surgical feature. Ovarian vessles are retroperitoneal structures that travel into the pelvic cavity without any turns. When the vessles are dissected off, they become intraperitoneal and make a sharp turn into the area where the ovary is attached. It is thought that ovarian blood flow can potentially be altered because of this anatomical change. By creating this tunnel, the ovarian vessles will be maintained in their retroperitoneal position, preventing from their sharp turn into the pelvis . The left lower port can be enlarged to 10 mm to introduce the needle. However, a 5 mm port can also be used. This requires removing the trocar and introducing the needle through the incision. The ovary is then sutured to the abdominal sidewall anteriorly using a nonabsorbable suture. In order to prevent the “drift” of the transposed ovaries back into the pelvic cavity, the transposed ovaries should be anchored securely to the peritoneum using transfixing nonabsorbable sutures  (Figure 10.7). In a case report of ovarian transposition wherein the ovaries were attached to the peritoneum using hemo-clips only, the ovaries were noted to slip back inside the pelvic cavity and the patient became menopausal following completion of pelvic radiation . Surgical clips should however be placed on the ovarian boundaries after suture fixation for radiographic identification to map out the ovaries during radiotherapy (Figure 10.8). The procedure is then completed after inspection of the pelvic cavity for hemostasis, irrigation, and removal of all debris and blood.
Both ovaries can be transposed above the level of the anterior-superior iliac spines without having to transect the fallopian tubes from their uterine origin. This allows for the possibility of spontaneous conception.
Figure 10.1 Using laparoscopic scissors, a small peritoneal incision is made in the lateral wall above the pelvic brim.
Figure 10.2 Transection of the utero-ovarian ligament.
Figure 10.3 Using the scissors, the peritoneum is incised medially and laterally along the length of the ovarian vessels to isolate the infundibulopelvic ligament and mobilize it away from the ureter.
Figure 10.4 Separation of the ovary from the fallopian tube.
Figure 10.5 Using a blunt grasper a tunnel is created in the retroperitoneum from the initial defect above the pelvic brim to the secondary defect in the area of the IP ligament.
Figure 10.6 The ovary is gently grasped and guided through the retroperitoneal channel.
Figure 10.7 Anchoring of the transposed ovaries to the peritoneum and the underlying fascia.
Figure 10.8 Ovarian transposition with placement of surgical clips after suturing that will help in radiographic identification in the future. Note that the vessels are under the peritoneal reflection.
Some of the potential complications of laparoscopic ovarian transposition include possible damage to the ovarian blood vessels, ovarian or fallopian tube infarction, abdominal pain, and ovarian torsion. There is also a small risk of possible radiation-induced cancer or metastasis of gynecological malignancies in the transpositioned ovaries [14,19]. Due to high rate of ovarian failure, ovarian transposition is not usually recommended in women older than 40 years. We also recommend ovarian suppression after transposition to avoid cyst formation, as this procedure may promote some ovarian dysfunction and cyst development.
After ovarian transposition, there is typically no need to reposition the ovaries for pregnancy to occur. However, additional surgery may be indicated to return the ovaries to their normal anatomic position to facilitate access for transvaginal oocyte retrieval for in vitro fertilization, as the procedure may complicate future oocyte retrieval.
10.6 Ovarian Tissue Harvesting and Cryopreservation
Ovarian tissue cryopreservation (OTC) is an emerging fertility preservation option for prepubertal girls and pediatric female patients with cancer, as controlled ovarian hyperstimulation is challenging in this population. The ovaries may not yet be as responsive to the exogenous gonadotropins used for controlled ovarian stimulation as part of assisted reproductive technologies (ART). OTC is also an evolving alternative for reproductive-aged women with cancer or benign conditions such as autoimmune diseases (e.g., multiple sclerosis and severe rheumatic diseases) or aplastic anemia, who may also need to undergo high doses of gonadotoxic chemotherapy or bone marrow transplant . This promising investigational option may also be used for adult female cancer patients with hormone-sensitive malignancies who are advised against controlled ovarian stimulation associated with in vitro fertilization, or in patients who cannot delay cancer treatment in order to undergo standard fertility preservation options including oocyte or embryo cryopreservation.
10.6.1 Ovarian Tissue Harvesting
Harvesting and cryopreservation of ovarian tissue prior to initiation of sterilizing chemotherapy has been developing over the past 20 years, initially in animal models and now with successful application to humans as well. Pregnancy and live birth rates following this procedure have continued to increase steadily, with an exponential rise. The number of reported live births as of June 2017 have exceeded 130 worldwide following transplantation of ovarian tissue [21–23].
OTC in the United States can currently only be offered under Institutional Review Board (IRB)-approved experimental protocols, and the technique is still considered experimental, but it may move toward broader clinical implementation with the use of appropriate selection criteria. At our institution, under an IRB-approved tissue registry, women desiring OTC undergo extensive counseling prior to the procedure. Recently a pediatric IRB has allowed children with cancer and other conditions whose treatments threaten future fertility to bank ovarian tissue as well. The experimental nature of this procedure is discussed with patients or families prior to signing a consent form. Harvesting of the ovarian tissue can be performed laparoscopically or via minilaparotomy and can involve a complete oophorectomy versus removing a portion of the ovary (a process known as ovarian decortication). In the prepubertal child, due to the small size of the ovaries, we recommend oophorectomy rather than decortication. The increased number of eggs in pre-pubertal children underscores the fact that smaller ovarian size in this population does not preclude ovarian tissue banking. In the following section, we outline our technique for laparoscopic ovarian tissue harvesting prior to OTC.