Fertility Preservation by Ovarian and Oocyte Cryopreservation (HFPP)

Study That Establishes the Potential of Fertility Preservation in Young Female Patients by Oocyte in Vitro Maturation and Cryopreservation and Ovarian Cortex Cryopreservation and Transplantation

Success rates of cancer treatment have increased significantly resulting in many girls and young women who are treated now and will be cancer survivors. Nevertheless, cancer treatment may result in long term side effects. Damage to the ovaries may result in serious difficulty to become pregnant in the future. The risk of this happening depends, among others upon patient's age, disease and type of treatment she undergoes. Medical research is continuously looking into ways to preserve female fertility by using less toxic protocols. Yet, keeping your eggs outside the body during treatment is an interesting option which as is routine for boys preserving sperm before cancer treatment. This research attempts to freeze eggs either in the ovarian tissue or individually.

Study Overview

• Status: Unknown
• Conditions: Female Patients Aged 5-35 Prior to Systemic Chemotherapy; With Significant Risk of Ovarian Toxicity
• Intervention / Treatment: Procedure: ovarian transplantation

Detailed Description

Advances in early detection and increasing success of chemotherapy have made cancer therapy a curable disease. In children and adolescents with cancer, cure rates approach 75%. These cure rates are achieved in great part due to the use of intensive chemotherapy, and in some cases, radiation. The use of these treatment modalities is associated with significant toxicity, including the potential for gonadal damage and subsequent reduced fertility. Aggressive chemotherapy is, however, usually gonadotoxic and results in infertility in many pediatric patients. Ovarian damage is drug and dose dependant and increases with patient age at treatment. Increasing numbers of young cancer survivors are therefore experiencing infertility related to their past cancer treatment. Having children thus becomes an important issue for young cancer patients.

Cryopreservation of sperm is an effective method that is offered to pre- and post-adolescent males. Female gametes were however, not readily amenable to cryopreservation though the use of vitrification recently resulted in improved results. Nevertheless, this method is not applicable for young girls as it requires prolonged induction of ovulation and vaginal sonography to complete aspiration of oocytes. Similarly, In vitro fertilization (IVF) may be offered only to patients beyond adolescence. Ovulation induction requires a few weeks delay in the initiation of cancer treatment.

Since ovarian stimulation is generally not a feasible option for young girls and adolescents, strategies for preserving fertility in these patients usually include ovarian cryopreservation, an experimental technology with some success in animal studies, recently resulting in few deliveries following human transplantations. Although the technique remains investigational, it is being increasingly offered to women undergoing cancer treatment. In prepubertal girls ovarian cryopreservation is the only option for potentially preserving ovarian function. As we and others have shown, it is probable that methods of ovarian transplantation with vascular anastomosis will be applied in the future.

We have recently recommended that following individual consultation by a multi-disciplinary team, all female pediatric cancer patients and their families should be counseled regarding side effects of chemotherapy and be offered ovarian preservation.

The methodology of ovarian cortex preservation, pioneered by Gosden is currently routine in many centers in a few countries. Nevertheless, it is realized that the future use of this cryopreserved ovarian cortex may be limited due to cellular injury during cryopreservation and due to the tissue ischemic damage following transplantation.

Furthermore, cryobanking of ovarian cortex preserves only the smallest (primordial and primary) follicles, since all preovulatory antral follicles, which contain GV stage oocytes will not survive the procedure. We thus currently propose to all patients undergoing ovarian cryopreservation to perform integrated oocyte aspiration from antral follicles of the tissue, followed by in vitro maturation (IVM) and oocyte cryopreservation as an additional fertility-preserving method. The aim of this study was to analyze oocyte detection and IVM success rates in young girls and adolescents using this combined method.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Assaf Ben Meir, MD; Phone Number: 97226776424; Email: assafb@hadassah.org.il

Study Locations

• Israel
  • Jerusalem, Israel, 91128
    • Recruiting
    • Hadassah University Hospital
    • Contact: Assaf Ben Meir, MD; Phone Number: 97226776424; Email: assafb@hadassah.org.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• patients before chemotherapy with significant risk to future fertility

Exclusion Criteria:

• high operative risk

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: OCCT; Patients referred to ovarian cryopreservation.	Procedure: ovarian transplantation; Patients will undergo laparoscopic oophorectomy, aspiration of oocytes and maturation followed by cryopreservation. In case of ovarian failure and approval by treating physicians, restoration of fertility will be attempted by thawing of oocytes or by transplantation of ovarian cortex to induce ovulation and obtain oocytes for fertilization and embryo transfer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
risks involved in laparoscopic oophorectomy	10 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Ability to restore fertility by ovarian cortex transplantation	10 years

Collaborators and Investigators

• Sponsor: Hadassah Medical Organization
• Investigators: Principal Investigator: Ariel Revel, MD, Hadassah University Hospital

Publications and helpful links

General Publications

• Revel A, Koler M, Simon A, Lewin A, Laufer N, Safran A. Oocyte collection during cryopreservation of the ovarian cortex. Fertil Steril. 2003 May;79(5):1237-9. doi: 10.1016/s0015-0282(02)04963-4. No abstract available.

Study record dates

Study Major Dates

• Study Start: January 1, 2000
• Study Completion (Anticipated): January 1, 2010

Study Registration Dates

• First Submitted: December 19, 2007
• First Submitted That Met QC Criteria: December 19, 2007
• First Posted (Estimate): December 21, 2007

Study Record Updates

• Last Update Posted (Estimate): December 21, 2007
• Last Update Submitted That Met QC Criteria: December 19, 2007
• Last Verified: January 1, 2002

More Information

Terms related to this study

• Keywords: chemotherapy, female, fertility preservation, gonadotoxicity; oophorectomy, in vitro maturation, ovarian cryopreservation,; oocyte cryopreservation, ovarian transplantation
• Other Study ID Numbers: 2819; 29-18/1/08