Hum. Reprod. Advance Access originally published online on July 3, 2008
Human Reproduction 2008 23(10):2266-2272; doi:10.1093/humrep/den244
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Two successful pregnancies following autotransplantation of frozen/thawed ovarian tissue
1 Laboratory of Reproductive Biology, Section 5712, University Hospital of Copenhagen, Blegdamsvej 9, Rigshospitalet, DK-2100 Copenhagen, Denmark 2 The Fertility Clinic, University Hospital of Copenhagen, Copenhagen, Denmark 3 Gynaecological Department at The Juliane Marie Centre for Women, Children and Reproduction, University Hospital of Copenhagen, Copenhagen, Denmark 4 Department of Gynaecology and Obstetrics, Aarhus University Hospital, Aarhus, Denmark 5 Reproductive Laboratory, Institute of Anatomy, University of Aarhus, Aarhus, Denmark
6 Correspondence address. Tel: +45-35455822; Fax: +45-35455824; E-mail: yding{at}rh.dk
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Abstract |
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BACKGROUND: Cryopreservation of the ovarian cortex with subsequent autotransplantation has, on an experimental basis, been performed to preserve fertility in women being treated for a malignant disease. The present study reports ovarian activity and pregnancies following autotransplantation of frozen/thawed ovarian tissue.
METHODS: One complete ovary was cryopreserved from each of six patients who were 26–35 years old prior to treatment. Tissue from three of the patients was transported 4–5 h on ice prior to cryopreservation. After a period of 17–32 months, orthotopic autotransplantation was performed replacing 20–60% of the tissue. Two patients received additional heterotopic transplants.
RESULTS: In all cases, the tissue restored menstrual cyclicity 14–20 weeks following transplantation. Four of the six women conceived following assisted reproduction: two women (who had the tissue transported 4–5 h prior to cryopreservation) each, based on the orthotopic transplanted tissue, delivered one healthy child (February 2007 and January 2008); one woman miscarriaged in gestational Week 7; and the other had a positive hCG test but no clinical pregnancy. The remaining two women did not become pregnant.
CONCLUSIONS: Two additional healthy children have been born as a result of the ovarian cryopreservation procedure. In both cases, the ovarian tissue was transported 4–5 h prior to freezing demonstrating that hospitals may offer cryopreservation without having the necessary expertise locally.
Key words: ovary/cryopreservation/autotransplantation/pregnancies/assisted reproduction
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Introduction |
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Girls and women suffering from malignant diseases, such as cancer, that require treatment with irradiation and/or gonadotoxic drugs, may as a consequence lose ovarian function and become infertile. The efficacy of treatment and survival rates for many types of such malignancies have increased over the past decades (McVie, 1999
) and as a consequence, more women will face the risk of premature ovarian failure. With prospects of living beyond cancer, salvage of fertility becomes of priority to both patients and physicians (Lee et al., 2006).
In addition to cryopreservation of oocytes and embryos, cold storage of the ovarian cortical tissue, which harbours the majority of the ovarian pool of follicles, has recently been developed in an attempt to circumvent the long-term ablative effect on reproductive performance by gonadotoxic treatment. When the patients are cured from their malignancy, the thawed tissue can be transplanted to those with treatment imposed ovarian failure, to restore ovarian function and normalize levels of gonadotrophins (Donnez et al., 2004, 2006; Oktay et al., 2004; Schmidt et al., 2005; Demeestere et al., 2006; Rosendahl et al., 2006).
Worldwide, three children have been reported to have been born thus far as a result of autotransplanting frozen/thawed ovarian tissue (Donnez et al., 2004, Meirow et al., 2005; Demeestere et al., 2007). One additional pregnancy has been reported following transplantation of fresh tissue first and subsequently frozen/thawed tissue (Silber et al., 2008). Although the procedure was introduced >10 years ago, experience with autotransplantation of frozen/thawed tissue is still very scarce and only a few cases have been reported, reflecting its experimental nature (Donnez et al., 2006, 2008). Further, a considerable amount of time often elapses after cancer treatment before patients feel prepared for autotransplantation and are considered cured and fit by their physicians. In addition, many hospitals lack the expertise to perform ovarian cryopreservation.
The present paper documents that autotransplantation of frozen/thawed ovarian tissue in combination with assisted reproduction may prove a valid method of fertility preservation.
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Materials and Methods |
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Cryopreservation of ovarian tissue
In Denmark, recovery of ovarian tissue for cryopreservation and autotransplantation of frozen/thawed tissue takes place in three centres, whereas the actual cryopreservation procedure itself is centralized to just one laboratory. The procedure has been approved by the Minister of Health and by the ethical committee of Copenhagen and Frederiksberg (J/KF/01/170/99). All patients had one entire ovary removed laparoscopically, except patient E who had her left ovary removed in 1992 due to a benign cyst and therefore only had one third of the remaining ovary removed for cryopreservation. The cortex was isolated, cut into fragments of 5 x 5 x (1–2) mm and cryopreserved as previously described (Schmidt et al., 2003b
). Out of 252 women having ovarian tissue cryopreserved, a total of six women have so far requested autotransplantation. The number of fragments cryopreserved from each of these patients A, B, C, D, E and F was 34, 29, 20, 20, 13 and 19, respectively. In addition, one small biopsy of the cortex was taken for histological evaluation.
Transportation of ovarian prior to cryopreservation
Patients D, E and F had the ovarian tissue transported on ice 4–5 h prior to cryopreservation (Schmidt et al., 2003a). Prior to transportation, the ovary was cut into two halves, rinsed for blood cells in PBS and, using sterile forceps, transferred into a 50 ml sterile tube containing 
20 ml ice-cold IVF medium. The tube was placed in an aluminium container with an aluminium-covered lid in order to protect the tissue from damaging effects of the irradiation used to screen packages before airfreight. The package contained enough ice to maintain low temperatures during the transport. Our usual procedure for cryopreservation of ovarian tissue was followed when the tissue arrived at the cryopreservation unit.
Autotransplantation
The gonadotoxic treatment given to each woman is given in Table I. Following chemotherapy, the remaining ovary showed no activity in any of the patients. All were amenorrhoeic and had experienced typical menopausal symptoms including hot flushes and consistent menopausal levels of FSH (37–135 IU/l at transplantation). All patients requested autotransplantation in order to become pregnant and after individual counselling and approval from the patients' oncologist or haematologist, transplantation was performed 17–32 months after cryopreservation (Table II). Patient A had given birth once prior to chemotherapy, whereas the other patients were nulliparous. Transplantation was performed as a combined laparoscopy/mini-laparotomy to subcortical pockets of the remaining follicle depleted ovary in all patients. The ovary was mobilized laparoscopically and made available through a 50 mm abdominal incision. Longitudinal incisions in the ovarian cortex created two pockets, one on each side of the ovary (Fig. 1). The fragments were aligned next to one another in the pockets. A small biopsy of the host ovary was taken to evaluate the presence of residual follicles. Patients B and C received additional autotransplantation to two subperitoneal pockets during the operation, in order to evaluate whether these sites supported follicular development better than the ovary. One was situated between the symphysis and the umbilicus on the anterior abdominal wall and the other on the lateral pelvic wall above the internal iliac artery, both available for transabdominal oocyte aspiration. The subperitoneal pockets were prepared laparoscopically in the parietal peritoneum and each harboured two to four tissue fragments. The tissue fragments were positioned with the cortical side facing the abdominal cavity. The fragments adhered to the pockets without individual fixation and the pockets were closed with staples and/or self-resorbing sutures.
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Autotransplantation
Between 20 and 60% of the cryopreserved tissue was transplanted (Table II). Three patients requested a second transplantation. Patient C received a second transplantation 26 months after the first because the original transplanted tissue had ceased to function; levels of FSH increased (>50 IU/l) and the patient again experienced menopausal symptoms. Patient D had the remaining tissue transplanted 14 months after the first operation. She still experienced normal menstrual cycles, but in order to augment the follicular pool and possibly her chances of pregnancy, she requested the remaining tissue. Patient F had the remaining frozen tissue grafted 9 months after the first transplantation, as FSH had increased to post-menopausal levels 2 months earlier and follicular development had ceased.
Time to return of ovarian activity
Return of ovarian activity was followed on regular intervals and included ultrasound examination and measurements of estradiol, FSH and luteinizing hormone (LH). All patients experienced resumption of ovarian activity following transplantation. Menopausal symptoms became less prominent after 8–10 weeks and the first menstruation appeared after 14–25 weeks (median 20 weeks). Ultrasound verification of follicular development occurred between 8 and 21 weeks (Table II). Concentrations of estradiol rose above the assay detection limit (<0.04 nmol/l) after 7 weeks and paralleled the decrease in FSH levels, which reached 20 IU/l at around 20 weeks following transplantation (Fig. 2). In patient A and D, the concentration of FSH thereafter fluctuated and was occasionally observed to be above 20 IU/l.
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Assisted reproduction
Due to the unknown lifespan and quality of the grafts, all patients were offered assisted reproduction to increase chances of conception. Initially, patients received conventional controlled ovarian stimulation using exogenous FSH stimulation following either standard long agonist or standard antagonist protocols. Contrary to normal women, only a few pre-ovulatory follicles developed in response to controlled ovarian stimulation in these patients. In reality, only two out of 25 cycles in which 13 included administration of high doses of gonadotrophins (
150 IU recombinant FSH per day starting on cycle Day 1) resulted in the development of more than two pre-ovulatory follicles. Subsequently, follicular development was supported by the administration of only 75 IU FSH per day from Day 2–4 of the menstrual cycle followed by antagonist administration when the leading follicle reached 14 mm in diameter. Irrespective of the number of pre-ovulatory follicles that developed, ovulation was induced when the leading follicle had a diameter of at least 17 mm using 10 000 IU hCG. Progesterone was given as luteal phase support. In total, 18 mature metaphase-II oocytes and 7 suboptimal oocytes were retrieved. Overall, fertilization occurred in 13 oocytes (72%), resulting in 11 embryo transfers (61%). The overall results of assisted reproduction are given in Table III.
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Patient A: Three treatment cycles resulted in retrieval of two mature oocytes; one failed to fertilize and one resulted in embryo transfer of one 3-cell embryo that did not implant. Thereafter, the patient discontinued treatment as the couple separated.
Patient B: Pre-ovulatory follicles developed at all three sites of transplantation. Oocyte retrieval from the three follicles that developed in the graft situated in the abdominal wall resulted in two mature oocytes, one of which was fertilized and resulted in a positive pregnancy test as previously reported (Schmidt et al. 2005). A pre-ovulatory follicle in the graft situated on the pelvic wall resulted in retrieval of a suboptimal oocyte that failed to fertilize. This couple have very busy jobs and requested assisted reproduction only when it would fit into their schedules.
Patient C: Follicular structures developed in the transplant located in the abdominal wall, but no pre-ovulatory follicle development was observed. A total of seven cycles resulted in aspiration of five mature oocytes plus three suboptimal oocytes from the host ovary. One embryo in each of two cycles were replaced and as a result of the last embryo transfer, the woman conceived. The clinical pregnancy did, however, not develop beyond Week 7. Fetal tissue was unfortunately not collected for caryotyping. She is now again attempting to conceive.
Patient D: After the tissue had restored ovarian function, the patient received administration of gonadotrophins in several cycles in order to augment development of pre-ovulatory follicles. Transfer of embryos was performed four times without implantation. After that and although the first transplant was still functional, the patient requested the remainder of her tissue transplanted in order to augment the follicular pool and possibly improve chances of conceiving. The patient experienced uterine adenomyosis, which after 2 months pituitary down-regulation with a GnRH agonist was removed during an operation 7 months after the second autotransplantation using the transverse H incision technique (Fujishita et al., 2004). The patient underwent one treatment cycle with assisted reproduction after the operation for adenomyosis, which resulted in retrieval of one mature oocyte and transfer of one 4-cell embryo that subsequently implanted. Following a normal uneventful pregnancy, she developed a slight pre-eclampsia close to term and delivered by Cesarean section. She gave birth to a healthy boy weighing 2600 g and 50 cm long in gestational Week 37 in January 2008.
Patient E: In her second menstrual cycle after the tissue had regained function, she received 150 IU rec-FSH (Puregon, Organon, Skovlunde, Denmark) per day starting on Day 1 and continued to the day of ovulation induction, which was induced by 10 000 hCG (Organon). Two oocytes were recovered and one 3-cell embryo was replaced. Subsequently, the patient conceived and experienced a normal uneventful pregnancy. A healthy girl weighing 3204 g and 52 cm long normal was delivered in gestational Week 39 in February 2007.
Patient F: Although the patient at the time of ovarian cryopreservation was almost 36 years of age, she still experienced regular menstrual cycles. However, there were no follicles observed in the cortex biopsy taken for histological evaluation in connection with the procedure. Despite the likelihood of a severely diminished ovarian follicle pool, it was decided, upon the patients request, to proceed with autotransplantation. The limited number of follicles in the transplants was reflected in the functional lifespan of the tissue, which lasted only 7 months during which one unsuccessful oocyte retrieval attempt was made.
Functional lifespan of the transplants
Table II shows the functional lifespan of the transplants as of January 2008. Except for patient F who was almost 36 years of age at the time of cryopreservation, all transplanted patients had ovarian activity for years following the transplantation. There is no obvious relation between longevity and age at cryopreservation and the amount of tissue transplanted. In several cases, the tissue is still active and the total functional lifespan remains to be determined. A biopsy of the in situ ovary at transplantation of patients B, C, E and F did not contain follicles, whereas the biopsies from patient A and D contained a few. Preliminary data for patients A, B and C has previously been published (Schmidt et al., 2005).
The two patients who had heterotropic grafts experienced pre-ovulatory follicular development independently of the transplantation site and equally often follicular development took place in the heterotropic transplanted tissue. The longevity of grafts did not seem to differ between the three implantation sites.
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With two additional childbirths following autotransplantation of frozen/thawed ovarian tissue, this study demonstrates that cryopreservation of ovarian cortical tissue in combination with assisted reproduction seems to be a useful way of preserving fertility in women facing gonadotoxic treatment. Following autotransplantation, none of the patients experienced relapse and ovarian function was restored in each case. The reproductive outcome for the six women reported here resulted in the birth of two healthy children, one woman achieving an unsuccessful clinical pregnancy, and one experienced a positive pregnancy test. It was explainable why the two remaining patients did not conceive: one separated from her partner and did not want to become pregnant after having had one unsuccessful embryo replacement. The ovarian reserve of the last patient was probably too low (she was almost 36 years of age at the time of cryopreservation) and only a few pre-ovulatory follicles developed upon transplantation. In total, 11 embryo replacements resulted in four positive pregnancy tests and the birth of two children. Collectively, these results demonstrate that frozen/thawed tissue sustains follicular development and results in reproductive outcome comparable to that obtained in conventional programmes of assisted reproduction when considering the use of frozen/thawed embryos.
Furthermore and equally important, the present study demonstrates the ability to transport ovarian tissue 4–5 h on ice prior to cryopreservation. Indeed, the two children born were a result of such transported tissue. This shows that the procedure may be offered also to those women, who today receive gonadotoxic treatment in hospitals without the necessary local expertise to perform ovarian cryopreservation. Allowing a transport time of 4–5 h will permit many hospitals to retrieve the ovarian tissue and forward it to a central cryopreserving unit. Therefore, the present results justify that increased numbers of young women at risk of entering treatment induced ovarian failure are offered the possibility of fertility preservation.
Taken together, cryopreservation of ovarian cortical tissue appears to be a valid method of fertility preservation in girls and young women, demonstrating an efficacy that seems to be similar to that of conventional fertility treatment with frozen/thawed embryos. It can readily be made available to many more women and the results justify a continued research effort in this area.
All patients receiving transplantation regained ovarian function suggesting that the cryopreservation procedure effectively preserved follicular viability. However, the present study is unable to document the fraction of follicles that actually survives the procedure, but patients having tissue frozen before the early-mid thirties experienced >1 year of ovarian function after having only a fraction of cortex from one ovary transplanted. This documents that the present cryopreservation protocol support survival of a substantial number of functional follicles. A fairly constant period of around 20 weeks was required for the development of the first pre-ovulatory follicle, irrespective of age, quantity of tissue replaced or the number of follicles present in the transplant, thereby confirming and extending observations by Donnez et al. (2008). This suggests that follicular growth and development is relatively unaffected by these factors. The transition time from the resting human primordial follicle to the pre-ovulatory stage has been estimated to be almost half a year (Gougeon, 1996). If only the very early stages in follicular development (i.e. primordial and primary follicles) survived cryopreservation, it would be expected that the period required for pre-ovulatory follicular development would last somewhat longer than the 2–3 months as observed in the present study. This suggests that some growing follicles do survive the cryopreservation procedure (i.e. later stages of follicular development) and resume growth after transplantation. This notion is supported by our findings of morphologically normal growing follicles in histological sections of frozen/thawed ovarian tissue (data not shown) and corroborate results of previous studies (Newton et al., 1996; Newton and Illingworth, 2001). However, restoration of ovarian function following transplantation in patients receiving gonadotoxic chemotherapy immediately prior to cryopreservation may take up to 8 months possibly reflecting the presence of only non-growing primordial follicles in the frozen/thawed tissue (Radford et al., 2001; Demeestere et al., 2006; Meirow et al., 2007). Studies using fresh, unfrozen ovarian tissue found a recovery period slightly shorter or similar to that reported here (Sanchez et al., 2007; Silber and Gosden, 2007). Although Patient C and D of the present study received an initial ABVD chemotherapy due to Hodgkin's disease prior to ovarian cryopreservation, the period between the first chemotherapy and retrieval of ovarian tissue prior to the second more severe chemotherapy was almost 2 years. Thus, follicular development was most likely unaffected by the first chemotherapy at the time of cryopreservation, explaining the 20 week period observed for the recovery of ovarian function also in these patients.
The three children previously born as a result of transplanting frozen/thawed ovarian tissue were, like those of the present study, conceived following orthotopic transplantation (Donnez et al., 2004; Meirow et al., 2005; Demeestere et al., 2007). Therefore, the remaining ovary seems to support follicular development in the transplant efficiently and appears favourable when compared with heterotopic transplants. Thereby, observations in the two women reported here confirm previous observations (Oktay et al., 2004). Assisted reproduction was used to optimize chances of pregnancy; the surgical procedure to the ovary and the position of grafts below the existing cortex could potentially interfere with normal ovulation and oocyte release. Also, normal function of the oviduct may subsequently be affected. However, two of the five children conceived following transplantation of fresh ovarian tissue between monozygotic twins occurred spontaneously (Silber and Gosden, 2007) and two of the children conceived following replacement of frozen/thawed tissue were the result of natural conception (Donnez et al., 2004; Demeestere et al., 2007). Thus, the importance of assisted reproduction in connection with transplantation of ovarian tissue remains to be determined.
Using the remaining ovary to host ovarian grafts eliminates precise knowledge of whether the follicle originates from the grafts or from the remaining ovary harbouring dormant follicles that potentially get activated by the surgical procedure. It is well known that women who receive chemotherapy may become menopausal for some years with elevated levels of FSH and then spontaneously regain ovarian activity again. In the present study, most of the patients received transplantation around 2 years after cryopreservation of the tissue and it cannot be excluded that some of the women spontaneously would have regained ovarian function after some time without the transplantation procedure being performed, although all the endocrine markers supported a post-menopausal state. However, primordial follicles were observed in the biopsy taken at transplantation from two patients in the present study, who both had been without menstrual activity for a considerable period of time. In Patient A, a few follicles were observed in the biopsy of the remaining ovary taken at transplantation. This woman experienced ovarian function for >3.5 years after having grafted only 20% of the cryopreserved tissue of one ovary. This may reflect that follicles of the host ovary were activated following transplantation and did participate in the maintaining ovarian activity for a relatively long period of 3.5 years. On the other hand, results obtained in Patient C suggest that follicles in the grafts do develop once transplanted. Ovarian function was restored after the first transplantation following a long period of amenorrhoea. Following a functional lifespan of 2 years, menstruations ceased again. Only after new follicles were transplanted with the second transplant, ovarian activity was restored giving strong support to actual follicular development in the grafted tissue. It is thus considered most likely that the two childbirths reported here actually derived from follicles present in the transplants.
An upper age limit for cryopreservation in the mid-thirties, as suggested previously (Donnez et al., 2006), was supported by this study. The patient, who was almost 36 years old at the time of cryopreservation only regained ovarian function for around half a year. However, slightly younger patients experienced years of ovarian function with half, or less, of their tissue transplanted and there is presently too little evidence to establish an upper age limit. At present, more data is required and we advise to make a dynamic assessment of the ovarian age based on the number of antral follicles and the levels of AMH and FSH. If the biological age seems to be lower than the chronological age of a patient in the mid-thirties, she may be offered cryopreservation with the information that her age introduces further risk to the procedure being able to successfully preserve fertility.
In contrast to women with normal ovarian function, administration of FSH in doses of 150 IU per day or more as often used in controlled ovarian stimulation was usually unable to augment the number of pre-ovulatory follicles developing in the ovarian transplants. This probably reflects that the pool of follicles is diminished and the number of growing follicles per cycle is more or less limited to those observed. In connection with assisted reproduction, our current approach is therefore to avoid the use of controlled ovarian stimulation with high doses of FSH, but we do often administer a small FSH dose of 75 IU per day in order to sustain follicular development in combination with an GnRH antagonist to avoid a premature LH surge when the follicle diameter exceeded 14 mm. Collection of oocytes and all IVF procedures were similar to the conventional applied techniques. Oocytes collected from heterotropic sites appear to behave similarly to those of orthotropic sites, although our experience is still limited.
In all cases reported here, the woman herself requested transplantation of ovarian tissue. This request was usually formulated in connection with a follow-up visit at the oncological centre and in each individual case, it was the decision of the treating oncologist or haematologist as to whether the patient was to receive transplantation or asked to wait. The decision was on one side based on the woman's desire, the risk of relapse and whether she was fit enough, and on the other side balanced against the risk of potentially introducing malignant cells via the transplant and the risk of the operation. The risk of transplanting tissue harvested at the time when the patient harboured neoplastic cells was based on available information in the literature, although this information was scarce at the time of transplantation. Although none of the patients experienced relapse as a result of tissue transplantation in this study, evaluation of the tissue prior to transplantation requires further attention including the effect that the tissue preparation procedure and the cryopreservation process itself has on survival of possible neoplastic cells in the transplant.
In conclusion, autotransplantation of frozen/thawed ovarian tissue seems to restore ovarian function with a good efficacy and the tissue does sustain transport of at least 5 h prior to freezing. The lifespan of the grafts is enough to secure sufficient time for the possibility of conceiving and in combination with assisted reproduction, two out of six women have given birth to healthy children as a result of this procedure. The present results encourage further development of the cryopreservation procedure for fertility preservation.
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Financial support from the Danish Cancer Foundation, The Danish Medical Research Council, the Danish Child Cancer Foundation and Hovedstadens Sygehusfællesskab is gratefully acknowledged.
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Demeestere I, Simon P, Buxant F, Robin V, Fernandez SA, Centner J, Englert Y. Ovarian function and spontaneous pregnancy after combined heterotopic and orthotopic cryopreserved ovarian tissue transplantation in a patient previously treated with bone marrow transplantation: case report. Hum Reprod (2006) 21:2010–2016.
Demeestere I, Simon P, Emiliani S, Delbaere A, Englert Y. Fertility preservation: successful transplantation of cryopreserved ovarian tissue in a young patient previously treated for Hodgkin's disease. Oncologist (2007) 12:1437–1442.
Donnez J, Dolmans MM, Demylle D, Jadoul P, Pirard C, Squifflet J, Martinez-Madrid A, van Langendonckt A. Livebirth after orthotopic transplantation of cryopreserved ovarian tissue. Lancet (2004) 364:1405–1410.[CrossRef][Web of Science][Medline]
Donnez J, Martinez-Madrid B, Jadoul P, van LA, Demylle D, Dolmans MM. Ovarian tissue cryopreservation and transplantation: a review. Hum Reprod Update (2006) 12:519–535.
Donnez J, Squifflet J, van Eyck A-S, Demylle D, Jadoul P, Van Langendonckt A, Dolmans A-M. Restoration of ovarian function in orthotopically transplanted cryopreserved ovarian tissue: a pilot experience. RBMOnline (2008) 16:694–704.
Fujishita A, Masuzaki H, Khan KN, Kitajima M, Ishimaru T. Modified reduction surgery for adenomyosis. A preliminary report of the transverse H incision technique. Gynecol Obstet Invest (2004) 57:132–138.[CrossRef][Web of Science][Medline]
Gougeon A. Regulation of ovarian follicular development in primates: facts and hypotheses. Endocr Rev (1996) 17:121–155.
Lee SJ, Schover LR, Partridge AH, Patrizio P, Wallace WH, Hagerty K, Beck LN, Brennan LV, Oktay K. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J Clin Oncol (2006) 24:2917–2931.
McVie JG. Cancer treatment: the last 25 years. Cancer Treat Rev (1999) 25:323–331.[CrossRef][Web of Science][Medline]
Meirow D, Levron J, Eldar-Geva T, Hardan I, Fridman E, Zalel Y, Schiff E, Dor J. Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy. N Engl J Med (2005) 353:318–321.
Meirow D, Levron J, Eldar-Geva T, Hardan I, Fridman E, Yemini Z, et al. Monitoring the ovaries after autotransplantation of cryopreserved ovarian tissue: endocrine studies, in vitro fertilization cycles, and live birth. Fertil Steril (2007) 87:418–422.
Newton H, Illingworth P. In-vitro growth of murine pre-antral follicles after isolation from cryopreserved ovarian tissue. Hum Reprod (2001) 16:423–429.
Newton H, Aubard Y, Rutherford A, Sharma V, Gosden R. Low temperature storage and grafting of human ovarian tissue. Hum Reprod (1996) 11:1487–1491.
Oktay K, Buyuk E, Veeck L, Zaninovic N, Xu K, Takeuchi T, Opsahl M, Rosenwaks Z. Embryo development after heterotopic transplantation of cryopreserved ovarian tissue. Lancet (2004) 363:837–840.[CrossRef][Web of Science][Medline]
Radford JA, Lieberman BA, Brison DR, Smith AR, Critchlow JD, Russell SA, et al. Orthotopic reimplantation of cryopreserved ovarian cortical strips after high-dose chemotherapy for Hodgkin's lymphoma. Lancet (2001) 357:1172–1175.[CrossRef][Web of Science][Medline]
Rosendahl M, Loft A, Byskov AG, Ziebe S, Schmidt KT, Andersen AN, Yding Andersen C. Biochemical pregnancy after fertilization of an oocyte aspirated from a heterotopic autotransplant of cryopreserved ovarian tissue: case report. Hum Reprod (2006) 21:2006–2009.
Sanchez M, Alama P, Gadea B, Soares SR, Simon C, Pellicer A. Fresh human orthotopic ovarian cortex transplantation: long-term results. Hum Reprod (2007) 22:786–791.
Schmidt KL, Ernst E, Byskov AG, Nyboe AA, Andersen CY. Survival of primordial follicles following prolonged transportation of ovarian tissue prior to cryopreservation. Hum Reprod (2003) a 18:2654–2659.
Schmidt KL, Byskov AG, Nyboe Andersen A, Muller J, Yding Andersen C. Density and distribution of primordial follicles in single pieces of cortex from 21 patients and in individual pieces of cortex from three entire human ovaries. Hum Reprod (2003) b 18:1158–1164.
Schmidt KL, Yding Andersen C, Loft A, Byskov AG, Ernst E, Andersen A N. Follow-up of ovarian function post-chemotherapy following ovarian cryopreservation and transplantation. Hum Reprod (2005) 20:3539–3546.
Silber SJ, Gosden RG. Ovarian transplantation in a series of monozygotic twins discordant for ovarian failure. N Engl J Med (2007) 356:1382–1384.
Silber SJ, Derosa M, Pineda J, Lenahan K, Grenia D, Gorman K, Gosden RG. A series of monozygotic twins discordant for ovarian failure: ovary transplantation (cortical versus microvascular) and cryopreservation. Hum Reprod (2008) 23:1531–1537.
Submitted on February 26, 2008; resubmitted on May 28, 2008; accepted on June 2, 2008.
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W.J. Dondorp and G.M.W.R. De Wert Fertility preservation for healthy women: ethical aspects Hum. Reprod., August 1, 2009; 24(8): 1779 - 1785. [Abstract] [Full Text] [PDF]
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V Isachenko, I Lapidus, E Isachenko, A Krivokharchenko, R Kreienberg, M Woriedh, M Bader, and J M Weiss Human ovarian tissue vitrification versus conventional freezing: morphological, endocrinological, and molecular biological evaluation Reproduction, August 1, 2009; 138(2): 319 - 327. [Abstract] [Full Text] [PDF]
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A. Wallin, M. Ghahremani, P. Dahm-Kahler, and M. Brannstrom Viability and function of the cryopreserved whole ovary: in vitro studies in the sheep Hum. Reprod., July 1, 2009; 24(7): 1684 - 1694. [Abstract] [Full Text] [PDF]
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V. Isachenko, E. Isachenko, and J.M. Weiss Human ovarian tissue: vitrification versus conventional freezing Hum. Reprod., July 1, 2009; 24(7): 1767 - 1768. [Full Text] [PDF]
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V. Fain-Kahn, C. Poirot, C. Uzan, M. Prades, S. Gouy, C. Genestie, P. Duvillard, and P. Morice Feasibility of ovarian cryopreservation in borderline ovarian tumours Hum. Reprod., April 1, 2009; 24(4): 850 - 855. [Abstract] [Full Text] [PDF]
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 J. S. Jeruss and T. K. Woodruff Preservation of Fertility in Patients with Cancer N. Engl. J. Med., February 26, 2009; 360(9): 902 - 911. [Full Text] [PDF]
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 R. Abir, B. Fisch, X.Y. Zhang, C. Felz, G. Kessler-Icekson, H. Krissi, S. Nitke, and A. Ao Keratinocyte growth factor and its receptor in human ovaries from fetuses, girls and women Mol. Hum. Reprod., February 1, 2009; 15(2): 69 - 75. [Abstract] [Full Text] [PDF]
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