Return Of Ovarian Function Research Articles

Ovarian tissue cryopreservation for fertility preservation before hematopoietic stem cell transplantation in patients with sickle cell disease: safety, ovarian function follow-up, and results of ovarian tissue transplantation.

To describe the experience of performing ovarian tissue cryopreservation (OTC) before hematopoietic stem cell transplantation (HSCT), among girls/women with severe sickle cell disease (SCD)(SS or S/β0-thalassemia) who are, besides the usual surgical risk, at risk of SCD-related complications during the fertility preservation procedure for improving their counseling and management. This retrospective study included 75 patients (girls/women) with SCD who have had OTC before myeloablative conditioning regimen (MAC) for HSCT. Characteristics of patients and data on OTC, ovarian status follow-up, and results of ovarian tissue transplantation (OTT) were collected in medical records. At OTC, the median (IQR 25-75; range) age of the patients was 9.6 (6.9-14.1; 3.6-28.3) years, 56/75 were prepubertal, and no SCD or surgery-related complications occurred. The median follow-up post-HSCT was > 9years. At the last follow-up, among prepubertal patients at HSCT, 26/56 were ≥ 15years old and presented with a premature ovarian insufficiency (POI), except 2, including the patient who had received an OTT to induce puberty. Eight were 13-15years old and presented for POI. The remaining 22 patients were under 13. Among the 19 patients who were menarche at HSCT, 2 died 6months post-HSCT and we do not have ovarian function follow-up for the other 2 patients. All the remaining patients (n = 15) had POI. Five patients had OTT. All had a return of ovarian function. One patient gave birth to a healthy baby. OTC is a safe fertility preservation technique and could be offered before MAC independent of the patient's age.

O-294 In-vitro maturation of oocytes from ovary tissue and ovarian longevity

Abstract Study question Is it possible to accomplish simple and robust in-vitro maturation (IVM) of oocytes from human ovarian tissue using principles of in vitro gametogenesis? Summary answer Many mature oocytes can be obtained from ovary tissue with simple media and no need for ovarian stimulation. What is known already IVM from ovarian tissue has been difficult in the past. To mature primordial follicles in vitro has become possible in mice utilizing eight ‘core genes’. It has not yet been performed in humans, and will be complicated. However, culturing germinal vesicle oocytes that have already become meiotically competent by in-vivo IVD and IVG would not be expected to be difficult. In addition, it is far easier to obtain many germinal vesicle oocytes with cortical dissection rather than with a needle. Study design, size, duration After the ovarian cortex has been dissected from the medulla and divided into slices for cryopreservation, the ‘spent’ medium in which the dissection took place was examined for free, loose cumulus complexes, and cultured for 24 to 48 hours. A variety of different culture media and gonadotrophin concentrations were employed, based on previously published data from in vitro gametogenesis in mice. Participants/materials, setting, methods A total of 119 female patients between age 2 and 35 years old underwent ovary cryopreservation (as well as in-vitro maturation of oocytes and IVM in the last 13 individuals) over a 24 year period. Up to 22 years later, 17 returned to have their ovary tissue thawed and transplanted back. Main results and the role of chance Every woman had return of ovarian function 5 months after transplant, similar to previous observations. As observed before, AMH concentration rose as FSH fell 4 months later. The grafts continued to work up to 8 years. Of the 17, 13 (76%) became pregnant with intercourse at least once, resulting in 19 healthy live births, including six live births from three women who had leukemia. Of the harvested germinal vesicle oocytes, 35% developed with simple culture media into mature metaphase II oocytes. Maturation of germinal vesicle to MII oocytes was detected between 24 and 48 h of exposure to the HCG-containing media. For most participants, the number of mature oocytes was what would be obtained from ovarian stimulation. Surprisingly, the success of IVM was not related to the specific media or to the concentration of gonadotrophin in the media. A variety of media and concentrations were intentionally used in light of now-established mechanisms of in-vitro oogenesis, to see if this understanding could be used for a simplification of IVM. Limitations, reasons for caution This is an early pilot study only, but the results are strikingly consistent with our extensive work with IVG in mice. Wider implications of the findings This study and the results of in-vitro gametogenesis reveal the limited role of the ovulatory cycle and ovarian stimulation in oocyte development other than for the oocyte to exit the ovary. The normal ovulation cycle is not needed for meiotic competence. Ovarian stimulation is only required for easy oocyte retrieval. Trial registration number Not applicable

In-vitro maturation and transplantation of cryopreserved ovary tissue: understanding ovarian longevity

Research questionIs it possible to use experience gained from 24 years of frozen ovarian transplantation, and from recent experience with in-vitro gametogenesis to accomplish simple and robust in-vitro maturation (IVM) of oocytes from human ovarian tissue? DesignA total of 119 female patients between age 2 and 35 years old underwent ovary cryopreservation (as well as in-vitro maturation of oocytes and IVM in the last 13 individuals) over a 24-year period. Up to 22 years later, 17 returned to have their ovary tissue thawed and transplanted back. ResultsEvery woman had a return of ovarian function 5 months after transplant, similar to previous observations. As observed before, anti-Müllerian hormone (AMH) concentration rose as FSH fell 4 months later. The grafts continued to work up to 8 years. Of the 17, 13 (76%) became pregnant with intercourse at least once, resulting in 19 healthy live births, including six live births from three women who had had leukaemia. Of the harvested germinal vesicle oocytes, 35% developed with simple culture media into mature metaphase II oocytes. ConclusionsThe authors concluded the following. First, ovary tissue cryopreservation is a robust method for preserving fertility even for women with leukaemia, without a need to delay cancer treatment. Second, many mature oocytes can often be obtained from ovary tissue with simple media and no need for ovarian stimulation. Third, ovarian stimulation only be necessary for removing the oocyte from the ovary, which can also be accomplished by simple dissection at the time of ovary freezing. Finally, pressure and just eight ‘core genes’ control primordial follicle recruitment and development.

Conception after chemotherapy: post-chemotherapy method of conception and pregnancy outcomes in breast cancer patients.

As the paradigm shifts towards improving cancer survivorship, an important concern for reproductive-aged women diagnosed with cancer is how their disease and its treatment will affect their future fertility. We sought to characterize pregnancy attempts and outcomes in breast cancer patients following chemotherapy. We conducted a prospective cohort study of women diagnosed with breast cancer seen between 2010 and 2019. A questionnaire was administered following cancer treatment with questions regarding oncologic and reproductive history and attempts and method of conception. Of 181 participants, 46 (25.4%) attempted to conceive following chemotherapy. Thirty-five patients (76.1%) had return of ovarian function. Of those, 34 patients (mean age 32.8 years) first attempted to conceive by intercourse, and 22 (64.7%) became pregnant, resulting in 17 live births. Of the remaining 12 who did not successfully conceive through intercourse, eight went on to try other methods, resulting in five additional pregnancies and one live birth. Twelve patients (mean age 34.6 years) proceeded directly to ART; of those, eight (66.7%) became pregnant, resulting in six live births. In breast cancer patients with return of ovarian function after chemotherapy, half were able to conceive by intercourse alone. In order to maximize reproductive potential in patients who have return of ovarian function, providers should offer natural conception as a reasonable option prior to the use of cryopreserved tissue. For those who did not attempt to conceive on their own, the use of pre-treatment cryopreserved eggs or embryos had a high likelihood of success.

Cryopreservation and transplantation of ovarian tissue: results from one center in the USA

PurposeTo report the results of cryopreserved ovary tissue transplantation for leukemia and other cancers, in a single US center.MethodsOne hundred eight females between age 6 and (median age 24) 35 were referred for possible ovary tissue cryopreservation over a 20-year period, with either slow freeze or vitrification. Thus far 13 patients returned up to 18 years later to have their tissue transplanted back.ResultsAll 13 patients had return of ovarian function 5 months post transplant with regular menstrual cycling. AMH rose to very high levels as the FSH declined to normal. Four months later, the AMH again declined to very low levels. Nonetheless, the grafts remained functional for up to 5 years or longer. Ten of the 13 (77%) became spontaneously pregnant at least once, resulting in 13 healthy babies. A total of 24 healthy babies have been born 11 from fresh transplanted ovarian tissue and 13 from cryopreserved transplanted ovarian tissue.Conclusions(1) Ovary tissue cryopreservation is a robust method for preserving a woman’s fertility. (2) Cortical tissue pressure may be a key regulator of primordial follicle arrest, recruitment, and ovarian longevity. (3) This is the only such series yet reported in the USA.

Assessing recrudescence of photoregressed Siberian hamster ovaries using in vitro whole ovary culture.

In vitro culture has been used to study different aspects of ovarian function; however, this technique has not been applied to study recrudescence, or the return of ovarian function in seasonally breeding species. In Siberian hamsters, exposure to inhibitory photoperiods induces declines in ovarian function, which are restored with photostimulation. Because these changes are mediated by changes in systemic gonadotropin (GT) secretion, we hypothesized that culturing photoregressed ovaries with GT would restore aspects of function and induce expression of key folliculogenic factors. Adult female Siberian hamsters were exposed to either long-day (LD; 16L:8D) or short-day (SD; 8L:16D) photoperiods for 14 weeks to maintain in vivo cyclicity or induce gonadal regression, respectively. Isolated ovaries were then cultured for 10 days with or without GT. Ovarian mass and messenger RNA (mRNA) expression of mitotic marker Pcna were increased in cultured SD ovaries (cSD) ovaries with GT as compared to without GT, with no changes noted among cultured LD (cLD) ovaries. Media estradiol and progesterone concentrations increased in both cLD and cSD ovaries cultured with GT as compared to without GT. No differences in follicle numbers or incidence of apoptosis were noted across groups. In addition, differential mRNA expression of folliculogenic growth factors ( Bmp-4, Ntf-3, Inh-α, Gdf-9, Igf-1, Has-2, and Cox-2) was observed in cSD treated with or without GT. Together, these results suggest that this in vitro model could be a useful tool to (a) study the return of function in photoregressed ovaries, and (b) to identify the specific roles folliculogenic factors play in ovarian recrudescence.

Cryopreservation and transplantation of ovary tissue: results from one center in the united states

To report the first series in the United States of cryopreserved ovary tissue transplantation using slow freeze or vitrification, for leukemia and other cancers. 13 patients over a 10 year period underwent thaw and transplantation of ovarian tissue that had been cryopreserved up to 20 years earlier when they were 20 years of age or younger. A single fertility center in a community hospital in the United states with a single team over 20 years. 108 females between age 6 and 35 were referred for possible ovary tissue cryopreservation over a 20 year period. Before 10 years ago only slow freeze was utilized, and after that only vitrification. Thus far only 13 patients whose tissue was frozen prior to age 35 returned up to 20 years later to have their tissue transplanted back, and have more than 2 years of post-transplant follow-up. No other ancillary treatment was administered. Detailed follow of hormones, menstruation, pregnancies, and live birth. All 13 cases had return of ovarian function 5 months post transplant with regular menstrual cycling. AMH rose to very high levels as the FSH declined to normal. 4 months later the AMH again declined to very low levels. Nonetheless the grafts remained functional for up to 5 years or longer. Ten of the 13 (85%) became spontaneously pregnant at least one, resulting in 13 healthy babies. Ovarian tissue cryopreservation and transplantation in young patients is a robust method of fertility preservation. Cortical tissue pressure may be a key regulator of primordial follicle recruitment and ovarian longevity.

Long term results with vitrification compared to slow freeze of ovarian tissue

To determine the best method of freezing, and report overall duration of function and live baby rate, after ovary tissue freeze and transplant for young cancer patients. 13 patients over an eight year period underwent thaw and transplantation of ovarian tissue that had been frozen up to 19 years earlier, with detailed follow-up of hormones, menstruation, pregnancies, and birth. Seven had undergone slow freeze, and 6 had undergone vitrification. All cancer patients varying from age 18 to age 31 who returned with POF to have their frozen ovary tissue transplanted back from 10 years ago to 2 years ago (over an 8 year period) are included in this retrospective cohort study. Their ovary tissue was frozen from 19 years ago to 5 years ago. Slow freeze was used until 10 years ago, after which only vitrification was employed exclusively. We now have long term follow-up of these 13 cases, with monthly evaluation of hormones, cycling, pregnancy, and live birth rate, and we can compare the results of slow freeze cases with those who had undergone vitrification. A total of 90 patients have undergone ovary tissue freeze, but only 13 have returned for the transplant. All patients had return of ovarian function from 4 to 5 months post-op. In all cases the return of function was accompanied by a very sharp rise in AMH for 4 months, with a subsequent decline to low levels. 8 of the 13 are still functioning. Duration of function varied from 561 days to 1,641 days (this graft is still functioning). Five of the 13 are still functioning for over 3 ½ years. There are 9 healthy babies (69%) from 10 pregnancies (76%). Slow freeze resulted in 5 healthy babies out of 7 transplants. Vitrification resulted in 4 healthy babies out of 6 transplants. However slow freeze cases had a shorter duration of function (614 to 1155 days) and 5 of the 7 are no longer functioning, whereas vitrification cases are all still functioning over 3 ½ years (1281 days to 1641 days). Ovary tissue freezing is a robust method for preserving fertility in young cancer patients. Slow freeze yields pregnancy results equivalent to vitrification. However vitrified transplants have a longer duration of function, verifying our in vitro report earlier of higher oocyte survival with vitrification compared to slow freeze.

Association between subclinical hypocalcemia in the first 3 days of lactation and reproductive performance of dairy cows

The objective of this study was to determine the effects of subclinical hypocalcemia on reproductive performance in dairy cows. In a prospective cohort study, 97 cows on 2 dairy farms with automatic milking systems were monitored for subclinical hypocalcemia. Animals were enrolled 7 ± 3 days prior to estimated calving date and three parity groups were defined based on the lactation that the animals were going to start: lactation = 1, lactation = 2, and lactation ≥3. Serum calcium concentration (Ca) was measured in all animals in the first 3 DIM and subclinical hypocalcemia (SCH) was defined as Ca ≤ 8.6 mg/dL; animals that presented a low Ca level during all 3 days were classified as chronic SCH (cSCH). Return to cyclicity during the voluntary waiting period was analyzed based on weekly progesterone concentrations measured in serum. Information on reproductive outcomes (i.e., number of breedings, pregnancy status, days open, etc.), were collected from on-farm software after all study cows had completed their study period. Chronic SCH was present in all parity groups with higher incidence in multiparous animals (20% of parity = 1, 32% of parity = 2; and 46% of parity ≥ 3 animals). The cSCH animals took longer to show active ovaries when compared to eucalcemic and SCH animals. In a multivariable Cox's Proportional Hazard model animals with normal Ca were 1.8 times more likely to return to cyclicity by the end of the voluntary waiting period when compared to cSCH animals. Animals with cSCH also had 0.27 odds of being pregnant at first service compared to eucalcemic cows when analyzed by multivariable logistic regression. Subclinical hypocalcemia had a negative effect on return of ovarian function during the voluntary waiting period and decreased the odds of pregnancy at first service. Those cows with cSCH had an even more pronounced impaired reproductive function than those with one subclinical measurement.

Ovarian Cancer in Children and Adolescents: Treatment and Reproductive Outcomes.

To review ovarian cancer cases in children and adolescents in Siriraj Hospital and assess the prognosis, recurrence of disease, and reproductive outcomes after treatment. A retrospective descriptive study was conducted in ovarian cancer patients 21 years and younger who had been treated at Siriraj Hospital between January 1990 and December 2009. Medical records were reviewed and relevant data were recorded. A total of 48 cases met the criteria; their mean age was 16.4 years. Abdominal distension was the major symptom. 91.6% were germ cell tumors and the remaining cases were sex cord-stromal and epithelial tumors. More than half (25/48 cases) presented with stage I disease. The most common used chemotherapy regimen for germ cell tumors was BEP (bloemycin, etoposide, cisplatin). Most of patients had favorable outcomes; 46/48 cases had complete remission and retained their good health at the time of the review. We had only one recurrent case and one dead case. Ten of contacted patients had married and 3 of them had successful full-term pregnancies. Ovarian malignancy in children and adolescents is a rare disease. The authors reported 48 cases in 20 year-period of work. Most of them have favorable outcomes. Return of ovarian function and fertility are the topics of interest.

Relationship between subclinical hypocalcemia and negative energy balance on the return of ovarian function during the voluntary waiting period of dairy cows

Early resumption of ovarian activity has been reported to be an important factor for the reproductive success of dairy cows because of improved uterine health and fertility. However, early lactation is characterized by a period of negative energy balance (NEB) and mobilization of fat reserves, which is highly associated with a longer postpartum anovulatory period. Moreover, the initiation of milk production and excessive utilization of calcium may lead to a subclinical hypocalcemic status that has been linked to deficient fatty acid metabolism in early lactation. Additionally, subclinical hypocalcemia (SCHP) can result in decreased progesterone (P4) and corpus luteum (CL) functionality, which further decreases reproductive performance in high-producing dairy cows. The objective of this study was to determine the influence of SCHP and NEB during the first 2 weeks in milk on the ovarian activity during the voluntary waiting period of dairy cows in herds with automatic milking systems (AMS).

Ovarian cysts are associated with return of ovarian function in female cancer survivors

Ovarian cysts are common and often benign in young women. In young women with cancer, evaluation of ovarian cysts is complicated by heighted concern for malignancy and lack of data on the natural history of cysts during cancer therapy. This study sought to describe the incidence and clinical significance of ovarian cysts in young women undergoing chemotherapy.

Ovary transplantation results: fresh vs frozen

OBJECTIVE: Ovarian tissue cryobanking to preserve fertility has been performed worldwide for over a decade, but until recently there was no way to assess the efficacy of this strategy for achieving healthy babies. A series of cases of premature ovarian failure (POF) at one center using the same microsurgical techniques for both fresh and frozen transplants, provided this opportunity. DESIGN: Consecutive series of women with premature ovarian failure (POF) who underwent either fresh (9), or frozen (3) ovarian transplantation. MATERIALS AND METHODS: Ten women with ovarian failure were recipients of 12 ovarian tissue transplants, 9 fresh and 3 frozen. In two patients, the reason for ovarian failure was cancer chemotherapy and radiation, and in eight patients the premature ovarian failure was idiopathic. RESULTS: There have been 14 pregnancies in these 10 women resulting in 11 healthy babies. Nine babies resulted from fresh ovary transplants, and two were from the 3 frozen transplants. All 11 children are normal and healthy. Two of the 11 healthy babies were in women who had received pelvic radiation as part of a bone marrow transplant. Duration of function of the grafts varied from only two years (where the donor ovary had a prior low antral follicle count) to over five years. All recipients of ovarian grafts, whether fresh or frozen, resumed menstrual cycling and ovulation within 4.5 months of transplantation and serum FSH returned to normal levels at that time. There was no apparent difference in return of ovarian function between the nine fresh and the three frozen grafts. CONCLUSION: Ovary transplantation with cortical grafts, whether fresh or frozen, appears to give robust results with most patients having healthy babies and all having resumption of ovulation. The long duration of function of most of the fresh grafts suggest there may be less damage from ischemia time than might have been previously thought.

Effects of Oral Contraception on Ovarian Histology

Follicutar development continues during contraceptive therapy but growth of the follicles failed to progress. Ovarian histology from wedge excision of the ovaries was studied in 43 users of the oral contraceptive pill — 31 during medication and 12 after medication. The result indicate that a prompt return of ovarian function and normalisation of ovarian histology occurs even after long-term use of the combined oral contraceptives.

Fresh Ovarian Tissue and Whole Ovary Transplantation

A series of monozygotic (MZ) twin pairs discordant for premature ovarian failure presented an unusual opportunity to study ovarian transplantation. Ten MZ twin pairs requested ovarian transplantation and nine have undergone transplantation with cryopreservation of spare tissue. Eight had a fresh cortical tissue transplant, one of whom received a second frozen-thawed transplant after the first ceased functioning at 3 years. One had a fresh microvascular transplant. All recipients reinitiated ovulatory menstrual cycles and normal day 3 serum follicle-stimulating hormone levels by 77 to 142 days. Seven have already conceived naturally (three twice). Currently, seven healthy infants have been delivered out of 10 pregnancies. The oldest transplant ceased functioning by 3 years, but then she conceived again after a frozen-thawed secondary transplant. There was no apparent difference in return of ovarian function between the nine fresh ovarian grafts and the one frozen graft. Ovarian transplantation appears to restore ovulatory function robustly. Ten pregnancies, leading to seven healthy infants, including one after cryopreservation, bode well for application to fertility preservation.

Resumption of ovarian function 20 years after chemotherapy-induced ovarian failure: a case report

To describe a case of resumption of ovarian function 20 years after chemotherapy-induced ovarian failure. Case report. University teaching hospital. A 33-year-old nulliparous black woman. Progesterone challenge, transvaginal ultrasound (TVS). Estradiol and FSH hormone levels. Confirmation that ovarian function returned in a women who presented with cyclic vaginal bleeding after a 20-year history of amenorrhea secondary to chemotherapy-induced ovarian failure. Return of ovarian function is possible after prolonged periods in women with chemotherapy-induced ovarian failure.

Menopause surveillance recommendations for patients with endocrine responsive breast cancer.

Abstract Abstract #1148 Background: Women aged under 55 receiving breast cancer treatment frequently experience temporary or permanent menopause as a result. Although defining menopause status in these patients is problematic it fundamentally influences subsequent medical management. No definitive data or consensus exists to guide what surveillance is required in these women, particularly with respect to treatment with aromatase inhibitors (AIs) and/or ovarian suppression and for contraceptive advice.The ENHANCE Group, first convened in Australia in 2006, consists of 19 members, comprising Medical Oncologists, Breast Surgeons, Endocrinologists, Gynaecologists and a Consumer Representative. The aim of the Group is to develop practical advice on the management of QoL and adverse event issues associated with hormonal therapy of breast cancer in areas where high-level evidence is insufficient to inform practice. The Group produces recommendations for healthcare professionals and information leaflets for patients. All recommendations are supported with the maximum evidence available together with broad expert opinion.
 Methods:A review of the literature identified information regarding the definition of menopause, tests of menopause status and likelihood of menopause following different adjuvant chemotherapy regimens. Data on the likelihood of return of ovarian function was also identified. In addition, the use and benefit of ovarian function suppression and AIs for treatment of different subpopulations of breast cancer patients was reviewed. Using this review and expert opinion provided by members of the Group, an algorithm for determination of menopausal category was developed. Management recommendations, according to menopausal category were then determined.
 Results:Five distinct menopause categories were identified: Premenopausal, Postmenopausal, Very Low, Low, and Moderate potential for ovarian function recovery. Menopausal status prior to adjuvant chemotherapy, type of adjuvant treatment, age, duration of amenorrhoea, oestradiol and FSH levels and use of tamoxifen determined placement into the categories. The algorithm includes suggested monitoring practice, both clinical and biochemical, for each of the menopause categories and guidance for patients who have had a hysterectomy. The recommendations indicate: (i)contraceptive advice according to age and menopause category; (ii)appropriate use of AIs with suggested monitoring practices; (iii)monitoring suggestions for patients where ovarian function suppression may be appropriate (iv)advice to be provided to patients to assist in monitoring menopausal status. A separate information sheet was developed to inform patients about menopause monitoring.
 Conclusions:Ovarian function can return after a considerable period of amenorrhoea in patients undergoing systemic treatment for breast cancer. Return of ovarian function influences endocrine treatment of breast cancer, but it is often difficult to monitor accurately, and an appropriate schedule has not been investigated. Our work provides evidence-based recommendations (including expert opinion) for best practice in this area. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1148.

A series of monozygotic twins discordant for ovarian failure: ovary transplantation (cortical versus microvascular) and cryopreservation

A series of monozygotic (MZ) twin pairs discordant for premature ovarian failure presented an unusual opportunity to study ovarian transplantation. Ten MZ twin pairs requested ovarian transplantation and eight have undergone transplantation with cryopreservation of spare tissue. Seven had a fresh cortical tissue transplant, one of whom received a second frozen-thawed transplant after the first ceased functioning at three years. One had a fresh microvascular transplant. All recipients reinitiated ovulatory menstrual cycles and normal Day 3 serum FSH levels by 77-142 days. Six have already conceived naturally (one twice). Currently, two healthy babies have been delivered, and another three pregnancies are ongoing. The oldest transplant functioned for 36 months, resulting in one child and one miscarriage. She conceived again after a frozen-thawed secondary transplant. There was no apparent difference in return of ovarian function between the eight fresh ovarian grafts and the one frozen graft. Ovarian transplantation appears to restore ovulatory function robustly. Successful pregnancies, including one after cryopreservation, bode well for application to fertility preservation.

Restoration of long term ovarian function after heterotopic autotransplantation of cryobanked human ovarian tissue: six year clinical experience

Although ovarian cryobanking followed by transplantation appears to be a valuable strategy to preserve fertility, there are many unknowns including long term ovarian function. To assess the long term ovarian function after ovarian transplantation, we analyzed 4 cases of heterotopic autotransplantation of frozen-thawed ovarian tissue during the 6 year period. Prospective clinical study. The study was approved by the institutional review board. Four study patients (three with cervical cancer, one with breast cancer) were identified, and one ovary from each patient was removed and cryopreserved. After cancer treatment, thawed ovarian tissue was transplanted to the space between the rectus muscle and fascia in the abdomen in all 4 patients. A follow-up was lost in one patient because of relapsed disease. Two patients have been followed for 4 years since ovarian transplantation in 2002. The third patient underwent ovarian transplantation in 2005. The restoration and maintenance of ovarian function was monitored by serial blood tests (FSH, LH, E2, Progesterone, Testosterone) and ultrasound. To investigate fertility restoration, three patients underwent IVF cycles. Between 12–20 weeks after transplantation, the return of the ovarian function was evidenced by the elevation of serum estradiol levels and by the decrease of FSH levels (below 15 mIU/ml). However, restored ovarian function lasted only 3–5 months, and 3 patients (except the one with relapsed disease) agreed to undergo second transplantation. The return of ovarian function after the second transplantation was faster in all three patients (between 1–3 months). In contrast to the first transplantation, long term ovarian function (lasting for 9–26 months) was established after the second transplantation. In addition, spontaneous ovulation were evidenced by a sequential hormonal profile and ultrasound. We were able to retrieve 6 oocytes from ovarian grafts in 2 patients between 2003 and 2005. Four MII oocytes were fertilized, developed in vitro for 3 days, and cryopreserved. 1) Long term ovarian function for more than 2 years was established after heterotopic autotransplantation of human ovarian tissue. 2) Follicles developed in the grafts were fertilized and developed up to 6 cell embryos in vitro. 3) When repeated ovarian transplantation is anticipated, transplantation to the hetertopic site can be advantageous, as it is technically easy, non-invasive, and less expensive.

Laparoscopic Medial Oophoropexy Prior to Radiation Therapy in an Adolescent with Hodgkin's Disease

Background Advances in radiation therapy have led to long term survival in young patients with Hodgkin's disease. Oophoropexy may reduce ovarian damage and preserve hormonal production and future fertility. When ovarian ligaments are shortened, incising the serosa parallel to the infundibulopelvic ligaments at laparoscopy permits the completion of a medial oophoropexy. Case An adolescent female underwent a laparoscopic medial oophoropexy prior to radiation therapy for Stage IIIB Hodgkin's disease. Due to shortened ovarian ligaments the ovaries could not be placed behind the uterus without excessive tension. The infundibulopelvic ligaments were sharply dissected off of the lateral pelvic sidewalls eliminating tension on the ligaments and allowing completion of the medial oophoropexy. Twenty-two months after completion of her radiation therapy the patient was normally menstruating and conceived spontaneously. Conclusion Laparoscopic dissection of the infundibulopelvic ligaments allowed for a medial oophoropexy to be performed in an adolescent patient and was associated with return of ovarian function after radiation therapy.