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.

PURPOSE: 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/ß0-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. METHODS: 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. RESULTS: 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 > 9 years. At the last follow-up, among prepubertal patients at HSCT, 26/56 were ≥ 15 years old and presented with a premature ovarian insufficiency (POI), except 2, including the patient who had received an OTT to induce puberty. Eight were 13-15 years old and presented for POI. The remaining 22 patients were under 13. Among the 19 patients who were menarche at HSCT, 2 died 6 months 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. CONCLUSION: OTC is a safe fertility preservation technique and could be offered before MAC independent of the patient's age.

Factors associated with the collection of isolated immature oocytes during ovarian tissue cryopreservation.

PURPOSE: To identify patient characteristics associated with successful isolated immature oocyte retrieval (IsO) during ovarian tissue cryopreservation (OTC) and to determine whether they are predictive of the collection of larger numbers of oocytes. METHODS: We retrospectively analyzed all patients undergoing OTC with IsO for fertility preservation over three years of activity at a university hospital. Univariate and multivariate analyses were used to identify the patients with the highest and lowest chances of oocyte recovery, and those with the largest numbers of oocytes. We also analyzed the correlation of IsO with the number of ovarian fragments collected and histological parameters. RESULTS: We analyzed 257 consecutive patients undergoing these procedures, at a median age of 17.1 years [0.3-38.3 years]. Isolated oocytes were obtained from 47.1% of patients, and IsO was more likely in patients with ovulatory cycles (63.0% vs. 38.6%; P≤ .001), without chemotherapy before OTC (61.4% vs. 33.1; P< .001) and with non-malignant diseases other than Turner syndrome (77.5%). Oocyte collection failure rates were highest in patients with Turner syndrome (OR 25.0, 95% CI 3.99-157.0; P< .001) or undergoing chemotherapy with alkylating agents before OTC (OR 37.6, 95% CI 8.36-168.8; P< .001). Prepubescent status (P= .043) and large numbers of ovarian fragments (P< .001) were associated with the retrieval of larger numbers of oocytes. Oocyte recovery was correlated with the presence of follicles in the medulla, but not with follicular density. CONCLUSION: The chances of IsO differ between patients. Identifying patients with the highest chances of success facilitates appropriate resource allocation.

Laparoscopic ovarian tissue harvesting and orthotopic ovarian cortex grafting for fertility preservation: less is more.

OBJECTIVE: To describe our surgical techniques for laparoscopic ovarian tissue harvesting and orthotopic ovarian cortex grafting (LOOCG). DESIGN: This video article uses surgical cases to demonstrate the detailed surgical techniques. Institutional Review Board approval was not required for this video presentation. SETTING: University hospital. PATIENT(S): Patients presenting with indication for fertility preservation by means of ovarian tissue harvesting and orthotopic ovarian cortex grafting (in case of setting up a high risk of gonadotoxicity treatment or patients presenting with a pathology with risk of premature ovarian failure). INTERVENTION(S): Ovarian tissue harvesting: The entire ovary is harvested by placing an EndoGIA stapler to ensure the control of infundibulopelvic ligament and then, after reloading, the section of the mesovarium. LOOCG one-step procedure: A large and superficial incision of the peritoneum is performed to create a peritoneal pocket. The fragments of ovarian cortex are secured with the use of nonresorbable surgical wire (Prolene 5.0) and introduced into the peritoneal pocket. The peritoneum is not closed after placing the graft. MAIN OUTCOME MEASURE(S): Value and feasibility of LOOCG. Restoration of endocrine function and fertility results. RESULT(S): Thirty-four patients were included from November 2011 to October 2017. LOOCG restored ovarian endocrine activity in 88.2% of cases. Ten patients had become pregnant (29.4%), and the same number gave birth to at least one child. CONCLUSION(S): Our surgical approach is simple, safe, and reproducible and seems to be as effective as previously described techniques. It deserves to be proposed to patients eligible for ovarian cortex grafting.

[Fertility and cancer]. / Fertilité et cancer.

Information about chemo and/or radiotherapy gonadotoxicity and about fertility preservation is essential. Sperm cryopreservation has to be systematically offered before gonadotoxic treatments. Efficiency of ovarian function preservation with GnRH agonists is still debated. A controlled ovarian stimulation is necessary before oocyte or embryo cryopreservation. It is only feasible if the treatment is not urgent and if the tumor is not hormone-sensitive. If the treatment is highly gonadotoxic, an ovarian tissue cryopreservation may be appropriate. It is the only fertility preservation technique feasible for prepubertal girls. It is now possible to preserve the fertility of prepubertal boys by cryopreservation of testicular tissue. It is essential to send patients and/or their parents to a specialized fertility preservation center.

Phenotyping and genetic studies of 357 consecutive patients presenting with premature ovarian failure.

OBJECTIVE: Premature ovarian failure (POF) encompasses a heterogeneous spectrum of conditions, with phenotypic variability among patients. The etiology of POF remains unknown in most cases. We performed a global phenotyping of POF women with the aim of better orienting attempts at an etiological diagnosis. DESIGN AND METHODS: We performed a mixed retrospective and prospective study of clinical, biological, histological, morphological, and genetic data relating to 357 consecutive POF patients between 1997 and 2008. The study was conducted at a reproductive endocrinology referral center. RESULTS: Seventy-six percent of the patients presented with normal puberty and secondary amenorrhea. Family history was present in 14% of the patients, clinical and/or biological autoimmunity in 14.3%. Fifty-six women had a fluctuating form of POF. The presence of follicles was suggested at ultrasonography in 50% of the patients, and observed in 29% at histology; the negative predictive value of the presence of follicles at ultrasonography was 77%. Bone mineral density alterations were found in 58% of the women. Eight patients had X chromosomal abnormalities other than Turner's syndrome, eight other patients evidenced FMR1 pre-mutation. Two other patients had autoimmune polyendocrine syndrome type 2 and 1. CONCLUSION: A genetic cause of POF was identified in 25 patients, i.e. 7% of the whole cohort. POF etiology remains most often undiscovered. Novel strategies of POF phenotyping are in such content mandatory to improve the rate of POF patients for whom etiology is identified.

Impact of infertility drugs after treatment of borderline ovarian tumors: results of a retrospective multicenter study.

OBJECTIVE: To evaluate safety and fertility outcome after the use of infertility drugs in patients who were treated conservatively for a borderline ovarian tumor (BOT). DESIGN: A retrospective multicenter study. SETTING: Centers participating in the French National Register on In Vitro Fertilization registry. PATIENT(S): Thirty patients who were treated for BOT who underwent ovarian induction (OI). INTERVENTION(S): Ovarian induction was performed in 25 patients for infertility after conservative surgery and before surgery for recurrent disease in 5 patients with a single ovary (emergency cases). MAIN OUTCOMES MEASURE(S): Fertility and recurrences rates. RESULT(S): The mean number of cycles of OI per patient was 2.6 (range, 1-10 cycles). The median follow-up time after treatment of the BOT was 93 months (range, 26-276 months). After a median follow-up time of 42 months after OI, 4 recurrences were observed (initial management was simple cystectomy in 3 of them). All recurrences were borderline tumors on a remaining ovary that had been treated by surgery alone. All patients are currently disease-free. Thirteen pregnancies were observed (10 pregnancies (40%) in the group of 25 patients who were treated for infertility). CONCLUSION(S): These results suggest that infertility drugs could be used safely in patients who experience infertility after conservative management of an early-stage BOT.