- Email: [email protected]
Robotic-assisted laparoscopic ovarian tissue transplantation
CASE REPORT Robotic-assisted laparoscopic ovarian tissue transplantation Munire Erman Akar, M.D.,a,b Alberto J. Carrillo, Ph.D.,a Jamie L. Jennell, M.D.,a and Tamer M. Yalcinkaya, M.D.a a b
Department of Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, North Carolina; and Department of Obstetrics and Gynecology, Akdeniz University School of Medicine, Antalya, Turkey
Objective: To describe a technique for frozen-banked ovarian tissue transplantation using robotic-assisted laparoscopy. Design: Case study. Setting: Academic tertiary care center. Patient(s): A 38-year-old patient in remission for non-Hodgkin lymphoma, whose ovarian tissue had been frozen for 3 years. Intervention(s): Robotic-assisted laparoscopic transplantation of thawed ovarian cortical tissue to the remaining ovary and peritoneum. Main Outcome Measure(s): Resumption of spontaneous menses, follicular development, and ovulation as demonstrated by ultrasound, and serum E2 and P levels. Result(s): The patient experienced cyclic spontaneous menstruation 6 months after the transplantation. Ovulation was confirmed by ultrasound and serum E2 and P levels at month 11 after surgery. Conclusion(s): Robotic-assisted laparoscopic surgery may be a good, minimally invasive alternative for the ovarian tissue transplantation procedure to restore ovarian function. (Fertil Steril 2011;95:1120.e5–e8. 2011 by American Society for Reproductive Medicine.) Key Words: Ovary, cryopreservation, transplantation, robotic-assisted laparoscopy
Ovarian tissue cryopreservation with subsequent autotransplantation has effectively preserved fertility in animal models, but its efficacy in women undergoing ablative chemotherapy is still uncertain (1–7). Nearly 100 transplantations have been performed in humans, but only nine of these have been reported to have a successful delivery from spontaneous conception (8, 10–12). Although laparoscopic transplantation of ovarian tissue has been described, most of the reported cases of transplantation have used a laparotomy approach to create small pockets on the remaining ovary that had been ablated by the chemotherapy. The cryopreserved pieces of ovarian cortical tissue were sutured into these pockets (8, 10–15). We considered that laparoscopy with robotic assistance would provide the same surgical access to the ovary, and we performed the first roboticassisted ovarian tissue autotransplantation.
MATERIALS AND METHODS Our patient was a 38-year-old female with a diagnosis of stage IV non-Hodgkin lymphoma at the age of 32; she received seven rounds of cyclophosphamide, adriamycin, vincristine, and prednisone, followed by right salpingo-oophorectomy for ovarian tissue cryopreservation. The cortical strips were cryopreserved in 1.5 M propanediol with the slow-freeze protocol at Cornell UniReceived June 2, 2010; revised September 13, 2010; accepted September 17, 2010; published online November 3, 2010. M.E.A. has nothing to disclose. A.J.C. has nothing to disclose. J.L.J. has nothing to disclose. T.M.Y. has nothing to disclose. Reprint requests: Munire Erman Akar, M.D., 131 Miller Street Comp Rehab, 2nd Floor, Center for Reproductive Medicine and Infertility, Winston-Salem, NC 27103 (E-mail: [email protected]).
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versity (16). Furthermore, she had six trials of EPOCH-R (i.e., etoposide, prednisone, vincristine, cyclophosphamide, adriamycin, and rituximab). During the following months, amenorrhea persisted and serum FSH levels were elevated (66.2 mIU/mL). After 3 years of remission, the patient requested to receive her cryopreserved ovarian tissue in order to relieve menopausal symptoms. The patient was informed of the benefits and possible risk of lymphoma cell transmission during transplantation, which has been reported to be low (9). The patient decided to undergo transplantation after consultation with the hematology, oncology, and pathology departments. The study was approved by the institutional review board of Wake Forest University, and the patient signed an informed consent indicating her desire to undergo the procedure. Under general, endotracheal anesthesia, the patient was positioned in the lithotomy position with pneumatic compression stockings for deep vein thrombosis prophylaxis. The abdomen and vagina were prepared. A 12-mm trocar was placed infraumbilical after a Veress needle was inserted, and pneumoperitoneum was created with CO2. Two lower, 8-mm robotic ports were placed in the left (along the anterior axillary line) and right lower quadrants, lateral to the inferior epigastric vessels. A fourth port (10 mm) was placed to the left of the umbilical port approximately midway between the umbilicus and the lateral ports as an accessory port. The da Vinci robot was docked and the surgeon continued to perform the surgery from the surgical console. After surveying the upper abdomen and pelvis, a Beaver blade was used to make a slit approximately 4 mm deep on the distal and lateral aspects of the left ovary.
Fertility and Sterility Vol. 95, No. 3, March 1, 2011 Copyright ª2011 American Society for Reproductive Medicine, Published by Elsevier Inc.
0015-0282/$36.00 doi:10.1016/j.fertnstert.2010.09.039
FIGURE 1
FIGURE 3
Transplantation of the cortical pieces to the remaining left ovary.
Return of ovarian function after ovarian tissue transplantation.
Akar. Laparoscopic ovarian tissue transplantation. Fertil Steril 2011.
The patient’s autologous cryopreserved ovarian cortical tissue was thawed by the Center for Reproductive Medicine staff and brought to the field in sterile condition on wet ice. Thawing of cortical pieces was performed by placing the vials in a 37 C water bath for 3 minutes. After thawing the vials, 12 pieces of cortex were removed with sterile forceps and transferred to a test tube. Tissue was rehydrated by washing 3–5 mL of the following solutions for 5 minutes at room temperature: 1.0 mol/L DMSO, 0.1 mol/L sucrose, mol/L DMSO, 0.1 mol/L sucrose, 0.1 mol/L sucrose, MHTF and 15% 0.2 SPS (17). One piece of ovarian cortex was placed in Bouin’s fixative for pathology. Fresh MHTFþ 15% SPS was added, and the tube was placed in ice for transport to the operation room. Two of the pieces
FIGURE 2 Transplantation of the cortical pieces to the tunnel created beneath the peritoneum.
Akar. Laparoscopic ovarian tissue transplantation. Fertil Steril 2011.
were placed into the medial incision. The first piece was 12 5 mm, whereas the other pieces were approximately 7 5 mm; these were sutured with sutures of 6-0 PDS on the medial aspect of the ovary. Next the ovary was flipped around with the help of laparoscopic Babcock forceps, and three pieces were placed into the slit on the lateral aspect of the ovary and also sutured in place (Fig. 1). Six more pieces were placed, carefully oriented with their cortical size facing the peritoneum into tunnels created subperitoneally superior to the left ovarian ligament and lateral to the left mesosalpinx (Fig. 2). The peritoneum was covered with 6-0 PDS.
RESULTS
Akar. Laparoscopic ovarian tissue transplantation. Fertil Steril 2011.
Fertility and Sterility
The patient had been pretreated with an injection of GnRH agonist (lupron depot, leuprolide acetate for depot suspension 3.75 mg; Abbott Laboratories, Chicago, IL) 6 days before surgery, and gestogen (provera, medroxy progesterone acetate 10 mg) to decrease endogenous FSH levels, as previously suggested for the reimplantation of cryopreserved ovarian tissue (18). The total time in the operating room was 4 hours. There were no intraoperative or postoperative complications. The patient was discharged on the same day. Six months after the procedure, FSH levels decreased and E2 levels increased to premenopausal levels (Fig. 3). In addition, the patient resumed menstruation cycles with relief of vasomotor symptoms 6 months after surgery. Ovulation was confirmed by ultrasonographic demonstration of follicular development to 16 mm on day 12, trilaminar endometrium of 7.58 mm (Fig. 4) and serum E2 of 252 pmol/L and serum P of 9.5 ng/mL at 11 months after surgery. The patient did not want to undergo ovulation induction. She had not conceived by the time of this writing.
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FIGURE 4 (A) Ultrasonography demonstrated a trilaminar endometrial thickness of 7.58 mm, 11 months after transplantation. (B) A 14-mm follicle increased to 16 mm, 3 days before the LH peak and a serum P level of 9.5 ng/mL.
Akar. Laparoscopic ovarian tissue transplantation. Fertil Steril 2011.
CONCLUSION Although ovarian tissue cryopreservation and transplantation are still considered experimental in humans, increasing numbers of pregnancies after this procedure have been reported from different centers around the world. Most of the reported cases of transplantation have used a laparotomy and consisted of suturing cryopreserved pieces of ovarian cortical tissue into small pockets that had been
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Akar et al.
created on the remaining ovary and at tunnels beneath the peritoneum (8, 10–15). Laparoscopic transplantation of the ovarian tissue has also been described previously (14, 15). However one of the problems with standard laparoscopy is the lack of fine motor control needed for suture placement. In contrast, robotic assistance allows a higher degree of motion within the patient. Patients have shorter
Laparoscopic ovarian tissue transplantation
Vol. 95, No. 3, March 1, 2011
hospitalization and fewer intraabdominal adhesions, and it can be reliably performed as a minimally invasive alternative. Although we can not entirely confirm that ovulation was from the transplanted thawed tissue, because of the persistence of elevated serum FSH levels and menopausal symptoms for 2 years prior to the transplantation procedure, we can assume that the ovulation was from the transplanted thawed tissue. Our case demonstrates that ovarian transplantation can be successful when ovarian tissue is cryopreserved after low-dose chemotherapy at a relatively advanced reproductive age. The maximal age for ovarian tissue cryopreservation has not been determined yet, but currently most centers limit the patient’s age to the middle thirties (8). The risk of developing premature ovarian failure depends on the age of the patients and chemotherapeutic agents used. Cytotoxic agents with high gonadotoxicity are as cyclophosphamide, chlorambucil, melphalan, busulfan, nitrogen mustard, and procarbazine (17). Although our patient was not an ideal candidate for autotransplantation, because of age and exposure to low-dose, high-risk chemotherapy before ovarian cryopreservation, ovarian function has
been observed with our technique. We could not evaluate the fertility potential accurately in this patient, because the patient elected to have none of the ovulation induction protocols suggested for cancer survivors. This case is the first ovarian tissue autotransplantation to use a robotic-assisted laparoscopic approach. We think that it is ideal to perform the ovarian transplantation with robotics, because of the minimally invasive approach while maintaining excellent freedom of motion within the pelvis for creating ovarian pockets and suturing. Although it is possible for skilled laparoscopic surgeons to do this kind of surgery without robotic assistance, the use of a robot facilitates making pockets and suturing atraumatically in the ovaries, which are located extremely laterally. Robotic-assisted laparoscopy may be a promising and minimally invasive alternative for ovarian tissue transplantation in children and women who are threatened with the loss of ovarian function owing to surgery, chemotherapy, or abdominal–pelvic radiation after the procedure is completed and the patient is found fit to proceed.
REFERENCES 1. Nugent D, Meirow D, Brook PF, Aubard Y, Gosden RG. Transposition in reproductive medicine: previous experience, present knowledge and future prospects. Hum Reprod Update 1997;3:267–80. 2. Gosden RG, Aubard Y. Transplantation of ovarian and testicular tissues (medical intelligence unit). Austin, TX: Landes Bioscience, 1996. 3. Sonmezer M, Oktay K. Fertility preservation in female patients. Hum Reprod Update 2004;10:251–66. 4. Parrott DMV. The fertility of mice with orthotopic ovarian grafts derived from frozen tissue. J Reprod Fertil 1960;1:230–41. 5. Gunasena KT, Villines TM, Critser ES, Critser JK. Live births after autologous transplant of cryopreserved mouse ovaries. Hum Reprod 1997;12:101–6. 6. Candy CJ, Wood MJ, Whittingham DG. Restoration of a normal reproductive life span after grafting of mouse ovaries. Hum Reprod 2000;15:1300–4. 7. Akar M, Oktay K. Restoration of ovarian endocrine function by ovarian transplantation. Trends Endocrinol Metab 2005;16:374–80. 8. Von Wolff M, Donnez J, Hovatta O, Keros V, Maltaris T, Montag M, et al. Cryopreservation and auto transplantation of human ovarian tissue prior
Fertility and Sterility
9.
10.
11.
12.
to cytotoxic therapy-a technique in its infancy but already successful in fertility preservation. Eur J Cancer 2009;45:1547–53. Meirow D, Hardan I, Dor J, et al. Searching for evidence of disease and malignant cell contamination in ovarian tissue stored from hematologic cancer patients. Hum Reprod 2008;23: 1007–13. Sanchez-Serrano M, Crespo J, Mirabet V, Cobo AC, Escriba MJ, Simon C, et al. Twins born after transplantation of human ovarian cortical tissue and oocyte vitrification. Fertil Steril 2010;93:268.e11–3. Meirow D, Levron J, Elder-Geva T, Hardan I, Fridman E, Zalel Y, et al. Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy. New Engl J Med 2005;353:318–21. Donnez J, Dolmans MM, Demylle D, Jadoul P, Pirard C, Squifflet J, et al. Restoration of ovarian function after orthotopic (intraovarin and periovarian) transplantation of cryopreserved ovarian tissue in a woman treated by bone marrow transplantation for sickle cell anaemia: case report. Hum Reprod 2006;21:183–8.
13. Ernst E, Bergholdt S, Stener Jorgensen J, Yding Andersen C. The first woman to give birth to two children following transplantation of frozen/ thawed ovarian tissue. Hum Reprod 2010;25: 1280–1. 14. Oktay K, Aydin BA, Karlikaya G. A technique for laparoscopic transplantation of frozen-banked ovarian tissue. Fertil Steril 2001;75:1212–6. 15. Donnez J, Squifflet J, Van Eyck A-S, Demylle D, Jadoul P, Van Langendonckt A, et al. Restoration of ovarian function after orthotopic (intraovarian and periovarian) transplantation of cryopreserved ovarian tissue: a pilot experience. Reprod Biomed 2008;16:694–704. 16. Oktay K, Karlikaya G, Aydin BA. Ovarian cryopreservation and transplantation: basic aspects. Mol Cell Endocrinol 2000;169:105–8. 17. Oktay K. New horizons in assisted reproductive technologies. Assist Reprod Techniques 1998; 8:51. 18. Donnez J, Martinez-Madrid B, Jadoul P, Van Langendonckt A, Demylle D, Dolmans MM. Ovarian tissue cryopreservation and transplantation: a review. Hum Reprod Update 2006a;12:519–35.
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Department of Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, North Carolina; and Department of Obstetrics and Gynecology, Akdeniz University School of Medicine, Antalya, Turkey
Objective: To describe a technique for frozen-banked ovarian tissue transplantation using robotic-assisted laparoscopy. Design: Case study. Setting: Academic tertiary care center. Patient(s): A 38-year-old patient in remission for non-Hodgkin lymphoma, whose ovarian tissue had been frozen for 3 years. Intervention(s): Robotic-assisted laparoscopic transplantation of thawed ovarian cortical tissue to the remaining ovary and peritoneum. Main Outcome Measure(s): Resumption of spontaneous menses, follicular development, and ovulation as demonstrated by ultrasound, and serum E2 and P levels. Result(s): The patient experienced cyclic spontaneous menstruation 6 months after the transplantation. Ovulation was confirmed by ultrasound and serum E2 and P levels at month 11 after surgery. Conclusion(s): Robotic-assisted laparoscopic surgery may be a good, minimally invasive alternative for the ovarian tissue transplantation procedure to restore ovarian function. (Fertil Steril 2011;95:1120.e5–e8. 2011 by American Society for Reproductive Medicine.) Key Words: Ovary, cryopreservation, transplantation, robotic-assisted laparoscopy
Ovarian tissue cryopreservation with subsequent autotransplantation has effectively preserved fertility in animal models, but its efficacy in women undergoing ablative chemotherapy is still uncertain (1–7). Nearly 100 transplantations have been performed in humans, but only nine of these have been reported to have a successful delivery from spontaneous conception (8, 10–12). Although laparoscopic transplantation of ovarian tissue has been described, most of the reported cases of transplantation have used a laparotomy approach to create small pockets on the remaining ovary that had been ablated by the chemotherapy. The cryopreserved pieces of ovarian cortical tissue were sutured into these pockets (8, 10–15). We considered that laparoscopy with robotic assistance would provide the same surgical access to the ovary, and we performed the first roboticassisted ovarian tissue autotransplantation.
MATERIALS AND METHODS Our patient was a 38-year-old female with a diagnosis of stage IV non-Hodgkin lymphoma at the age of 32; she received seven rounds of cyclophosphamide, adriamycin, vincristine, and prednisone, followed by right salpingo-oophorectomy for ovarian tissue cryopreservation. The cortical strips were cryopreserved in 1.5 M propanediol with the slow-freeze protocol at Cornell UniReceived June 2, 2010; revised September 13, 2010; accepted September 17, 2010; published online November 3, 2010. M.E.A. has nothing to disclose. A.J.C. has nothing to disclose. J.L.J. has nothing to disclose. T.M.Y. has nothing to disclose. Reprint requests: Munire Erman Akar, M.D., 131 Miller Street Comp Rehab, 2nd Floor, Center for Reproductive Medicine and Infertility, Winston-Salem, NC 27103 (E-mail: [email protected]).
1120.e5
versity (16). Furthermore, she had six trials of EPOCH-R (i.e., etoposide, prednisone, vincristine, cyclophosphamide, adriamycin, and rituximab). During the following months, amenorrhea persisted and serum FSH levels were elevated (66.2 mIU/mL). After 3 years of remission, the patient requested to receive her cryopreserved ovarian tissue in order to relieve menopausal symptoms. The patient was informed of the benefits and possible risk of lymphoma cell transmission during transplantation, which has been reported to be low (9). The patient decided to undergo transplantation after consultation with the hematology, oncology, and pathology departments. The study was approved by the institutional review board of Wake Forest University, and the patient signed an informed consent indicating her desire to undergo the procedure. Under general, endotracheal anesthesia, the patient was positioned in the lithotomy position with pneumatic compression stockings for deep vein thrombosis prophylaxis. The abdomen and vagina were prepared. A 12-mm trocar was placed infraumbilical after a Veress needle was inserted, and pneumoperitoneum was created with CO2. Two lower, 8-mm robotic ports were placed in the left (along the anterior axillary line) and right lower quadrants, lateral to the inferior epigastric vessels. A fourth port (10 mm) was placed to the left of the umbilical port approximately midway between the umbilicus and the lateral ports as an accessory port. The da Vinci robot was docked and the surgeon continued to perform the surgery from the surgical console. After surveying the upper abdomen and pelvis, a Beaver blade was used to make a slit approximately 4 mm deep on the distal and lateral aspects of the left ovary.
Fertility and Sterility Vol. 95, No. 3, March 1, 2011 Copyright ª2011 American Society for Reproductive Medicine, Published by Elsevier Inc.
0015-0282/$36.00 doi:10.1016/j.fertnstert.2010.09.039
FIGURE 1
FIGURE 3
Transplantation of the cortical pieces to the remaining left ovary.
Return of ovarian function after ovarian tissue transplantation.
Akar. Laparoscopic ovarian tissue transplantation. Fertil Steril 2011.
The patient’s autologous cryopreserved ovarian cortical tissue was thawed by the Center for Reproductive Medicine staff and brought to the field in sterile condition on wet ice. Thawing of cortical pieces was performed by placing the vials in a 37 C water bath for 3 minutes. After thawing the vials, 12 pieces of cortex were removed with sterile forceps and transferred to a test tube. Tissue was rehydrated by washing 3–5 mL of the following solutions for 5 minutes at room temperature: 1.0 mol/L DMSO, 0.1 mol/L sucrose, mol/L DMSO, 0.1 mol/L sucrose, 0.1 mol/L sucrose, MHTF and 15% 0.2 SPS (17). One piece of ovarian cortex was placed in Bouin’s fixative for pathology. Fresh MHTFþ 15% SPS was added, and the tube was placed in ice for transport to the operation room. Two of the pieces
FIGURE 2 Transplantation of the cortical pieces to the tunnel created beneath the peritoneum.
Akar. Laparoscopic ovarian tissue transplantation. Fertil Steril 2011.
were placed into the medial incision. The first piece was 12 5 mm, whereas the other pieces were approximately 7 5 mm; these were sutured with sutures of 6-0 PDS on the medial aspect of the ovary. Next the ovary was flipped around with the help of laparoscopic Babcock forceps, and three pieces were placed into the slit on the lateral aspect of the ovary and also sutured in place (Fig. 1). Six more pieces were placed, carefully oriented with their cortical size facing the peritoneum into tunnels created subperitoneally superior to the left ovarian ligament and lateral to the left mesosalpinx (Fig. 2). The peritoneum was covered with 6-0 PDS.
RESULTS
Akar. Laparoscopic ovarian tissue transplantation. Fertil Steril 2011.
Fertility and Sterility
The patient had been pretreated with an injection of GnRH agonist (lupron depot, leuprolide acetate for depot suspension 3.75 mg; Abbott Laboratories, Chicago, IL) 6 days before surgery, and gestogen (provera, medroxy progesterone acetate 10 mg) to decrease endogenous FSH levels, as previously suggested for the reimplantation of cryopreserved ovarian tissue (18). The total time in the operating room was 4 hours. There were no intraoperative or postoperative complications. The patient was discharged on the same day. Six months after the procedure, FSH levels decreased and E2 levels increased to premenopausal levels (Fig. 3). In addition, the patient resumed menstruation cycles with relief of vasomotor symptoms 6 months after surgery. Ovulation was confirmed by ultrasonographic demonstration of follicular development to 16 mm on day 12, trilaminar endometrium of 7.58 mm (Fig. 4) and serum E2 of 252 pmol/L and serum P of 9.5 ng/mL at 11 months after surgery. The patient did not want to undergo ovulation induction. She had not conceived by the time of this writing.
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FIGURE 4 (A) Ultrasonography demonstrated a trilaminar endometrial thickness of 7.58 mm, 11 months after transplantation. (B) A 14-mm follicle increased to 16 mm, 3 days before the LH peak and a serum P level of 9.5 ng/mL.
Akar. Laparoscopic ovarian tissue transplantation. Fertil Steril 2011.
CONCLUSION Although ovarian tissue cryopreservation and transplantation are still considered experimental in humans, increasing numbers of pregnancies after this procedure have been reported from different centers around the world. Most of the reported cases of transplantation have used a laparotomy and consisted of suturing cryopreserved pieces of ovarian cortical tissue into small pockets that had been
1120.e7
Akar et al.
created on the remaining ovary and at tunnels beneath the peritoneum (8, 10–15). Laparoscopic transplantation of the ovarian tissue has also been described previously (14, 15). However one of the problems with standard laparoscopy is the lack of fine motor control needed for suture placement. In contrast, robotic assistance allows a higher degree of motion within the patient. Patients have shorter
Laparoscopic ovarian tissue transplantation
Vol. 95, No. 3, March 1, 2011
hospitalization and fewer intraabdominal adhesions, and it can be reliably performed as a minimally invasive alternative. Although we can not entirely confirm that ovulation was from the transplanted thawed tissue, because of the persistence of elevated serum FSH levels and menopausal symptoms for 2 years prior to the transplantation procedure, we can assume that the ovulation was from the transplanted thawed tissue. Our case demonstrates that ovarian transplantation can be successful when ovarian tissue is cryopreserved after low-dose chemotherapy at a relatively advanced reproductive age. The maximal age for ovarian tissue cryopreservation has not been determined yet, but currently most centers limit the patient’s age to the middle thirties (8). The risk of developing premature ovarian failure depends on the age of the patients and chemotherapeutic agents used. Cytotoxic agents with high gonadotoxicity are as cyclophosphamide, chlorambucil, melphalan, busulfan, nitrogen mustard, and procarbazine (17). Although our patient was not an ideal candidate for autotransplantation, because of age and exposure to low-dose, high-risk chemotherapy before ovarian cryopreservation, ovarian function has
been observed with our technique. We could not evaluate the fertility potential accurately in this patient, because the patient elected to have none of the ovulation induction protocols suggested for cancer survivors. This case is the first ovarian tissue autotransplantation to use a robotic-assisted laparoscopic approach. We think that it is ideal to perform the ovarian transplantation with robotics, because of the minimally invasive approach while maintaining excellent freedom of motion within the pelvis for creating ovarian pockets and suturing. Although it is possible for skilled laparoscopic surgeons to do this kind of surgery without robotic assistance, the use of a robot facilitates making pockets and suturing atraumatically in the ovaries, which are located extremely laterally. Robotic-assisted laparoscopy may be a promising and minimally invasive alternative for ovarian tissue transplantation in children and women who are threatened with the loss of ovarian function owing to surgery, chemotherapy, or abdominal–pelvic radiation after the procedure is completed and the patient is found fit to proceed.
REFERENCES 1. Nugent D, Meirow D, Brook PF, Aubard Y, Gosden RG. Transposition in reproductive medicine: previous experience, present knowledge and future prospects. Hum Reprod Update 1997;3:267–80. 2. Gosden RG, Aubard Y. Transplantation of ovarian and testicular tissues (medical intelligence unit). Austin, TX: Landes Bioscience, 1996. 3. Sonmezer M, Oktay K. Fertility preservation in female patients. Hum Reprod Update 2004;10:251–66. 4. Parrott DMV. The fertility of mice with orthotopic ovarian grafts derived from frozen tissue. J Reprod Fertil 1960;1:230–41. 5. Gunasena KT, Villines TM, Critser ES, Critser JK. Live births after autologous transplant of cryopreserved mouse ovaries. Hum Reprod 1997;12:101–6. 6. Candy CJ, Wood MJ, Whittingham DG. Restoration of a normal reproductive life span after grafting of mouse ovaries. Hum Reprod 2000;15:1300–4. 7. Akar M, Oktay K. Restoration of ovarian endocrine function by ovarian transplantation. Trends Endocrinol Metab 2005;16:374–80. 8. Von Wolff M, Donnez J, Hovatta O, Keros V, Maltaris T, Montag M, et al. Cryopreservation and auto transplantation of human ovarian tissue prior
Fertility and Sterility
9.
10.
11.
12.
to cytotoxic therapy-a technique in its infancy but already successful in fertility preservation. Eur J Cancer 2009;45:1547–53. Meirow D, Hardan I, Dor J, et al. Searching for evidence of disease and malignant cell contamination in ovarian tissue stored from hematologic cancer patients. Hum Reprod 2008;23: 1007–13. Sanchez-Serrano M, Crespo J, Mirabet V, Cobo AC, Escriba MJ, Simon C, et al. Twins born after transplantation of human ovarian cortical tissue and oocyte vitrification. Fertil Steril 2010;93:268.e11–3. Meirow D, Levron J, Elder-Geva T, Hardan I, Fridman E, Zalel Y, et al. Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy. New Engl J Med 2005;353:318–21. Donnez J, Dolmans MM, Demylle D, Jadoul P, Pirard C, Squifflet J, et al. Restoration of ovarian function after orthotopic (intraovarin and periovarian) transplantation of cryopreserved ovarian tissue in a woman treated by bone marrow transplantation for sickle cell anaemia: case report. Hum Reprod 2006;21:183–8.
13. Ernst E, Bergholdt S, Stener Jorgensen J, Yding Andersen C. The first woman to give birth to two children following transplantation of frozen/ thawed ovarian tissue. Hum Reprod 2010;25: 1280–1. 14. Oktay K, Aydin BA, Karlikaya G. A technique for laparoscopic transplantation of frozen-banked ovarian tissue. Fertil Steril 2001;75:1212–6. 15. Donnez J, Squifflet J, Van Eyck A-S, Demylle D, Jadoul P, Van Langendonckt A, et al. Restoration of ovarian function after orthotopic (intraovarian and periovarian) transplantation of cryopreserved ovarian tissue: a pilot experience. Reprod Biomed 2008;16:694–704. 16. Oktay K, Karlikaya G, Aydin BA. Ovarian cryopreservation and transplantation: basic aspects. Mol Cell Endocrinol 2000;169:105–8. 17. Oktay K. New horizons in assisted reproductive technologies. Assist Reprod Techniques 1998; 8:51. 18. Donnez J, Martinez-Madrid B, Jadoul P, Van Langendonckt A, Demylle D, Dolmans MM. Ovarian tissue cryopreservation and transplantation: a review. Hum Reprod Update 2006a;12:519–35.
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