Cryopreservation of Ovarian Tissue: Reimplantation Rate and Effects on Ovarian Function

February 14, 2025 updated by: IRCCS Azienda Ospedaliero-Universitaria di Bologna

Cryopreservation Of Ovarian Tissue: Assessment Of Reimplantation Rate And Effects On Ovarian Function

The prevalence of POI in the general population is about 1%. In recent years, the incidence of iatrogenic POI in cancer women is increasing: 4% of patients of fertile age are diagnosed with neoplasms and gonadal treatments that can sterilize them, such as chemotherapy and radiotherapy. Preserving fertility is a key objective for many cancer patients.

Before gonadotoxic treatments, patients in the post-pubertal age with future desire for pregnancy may opt for two main methods of preservation of fertility (FP): egg cryopreservation (OC) after ovarian stimulation and cryopreservation of ovarian tissue (OTC). An important limitation of the latter technique is the reduced number of patients who return to use the cryopreserved material, leading to a negative impact on the evaluation of the effectiveness of the procedure. The best way to maximise the effectiveness of the procedure in clinical and economic terms would be to increase the number of patients who continue the cryopreservation path by completing it with subsequent reimplantation. It would also be useful to improve the follow-up of these patients by evaluating their ovarian function over time, before and after the removal and reimplantation, through the study of bone metabolism, cardiovascular risk and psychological function in these women.

Study Overview

Status

Recruiting

Conditions

Cryopreservation

Detailed Description

Premature ovarian failure (POI) is a clinical syndrome defined by the loss of ovarian activity before age 40. POI is characterized by amenorrhea or oligomenorrhea with elevated gonadotropins, low estradiol and serious consequences on fertility. The prevalence of POI in the general population is about 1%. In recent years, the incidence of iatrogenic POI in cancer women is increasing: 4% of patients of fertile age are diagnosed with neoplasms and gonadal treatments that can sterilize them, such as chemotherapy and radiotherapy. Preserving fertility is a key objective for many cancer patients. The American Society of Clinical Oncology (ASCO) says that healthcare professionals who care for cancer patients should address infertility as soon as possible before starting treatment. In addition, the demand for fertility preservation for non-oncology diseases as well as personal reasons has increased significantly, and meeting this demand is a major challenge.

In these cases, OTC, a technique which has emerged from its experimental phase, now safe and with an increasing number of successes, is considered as the unique option for FP. Also, unlike OC, OTC allows the induction of puberty in prepubertal patients, restoration of ovarian hormonal function for 3-7 years, until the graft is active, and may be renewed by subsequent reimplantation of orthotopic or heterotropic tissue.

An important limitation of this technique is the reduced number of patients who return to use the cryopreserved material, which has a negative impact on the evaluation of the effectiveness of the procedure. Several causes in the period between ovarian sampling and transplantation may justify this low rate, including: i) loss of desire for pregnancy; ii) recurrence of cancer; iii) death of the patient; iv) financial reasons; ) fear of cancer recurrence due to contamination of ovarian sampling; vi) occurrence of spontaneous pregnancies; vii) absence of current partner.

The best way to maximise the effectiveness of the procedure in clinical and economic terms would be to increase the number of patients who continue the cryopreservation path by completing it with subsequent reimplantation. It would also be useful to improve the follow-up of these patients by evaluating their ovarian function over time, before and after the removal and reimplantation, through the study of bone metabolism, cardiovascular risk and psychological function in these women.

Study Type

Observational

Enrollment (Estimated)

400

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Renato Seracchioli, MD
Phone Number: +390512143944
Email: renato.seracchioli@aosp.bo.it

Study Contact Backup

Name: Rossella Vicenti
Email: rossella.vicenti@unibo.it

Study Locations

Italy
- - Bologna, Italy, 40138
    - Recruiting
    - IRCCS Azienda Ospedaliero-Universitaria di Bologna
    - Principal Investigator:
      
      Renato Seracchioli, MD
    - Contact:
      
      Renato Seracchioli, MD
      
      Phone Number: +390512143944
      
      Email: renato.seracchioli@aosp.bo.it
    - Contact:
      
      Rossella Vicenti
      
      Email: rossella.vicenti@unibo.it

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Child
Adult

Accepts Healthy Volunteers

Sampling Method

Non-Probability Sample

Study Population

Women aged between 13 and 55 years old suffering from oncological pathologies that require gonadotoxic treatments and who undergo prior to these treatments a collection of ovarian tissue for cryopreservation and possible subsequent orthotopic or heterotropic reimplantation in order to restore ovarian function and fertility

Description

Inclusion Criteria:

Age: 13-55 years
Suffering from diseases that require gonadotropic treatments
Have been subjected to sampling and cryopreservation of ovarian tissue at the Operative Unit of Gynecology and Pathophysiology of Human Reproduction of the Sant'Orsola Polyclinic in Bologna
Informed Consent Acquisition

Exclusion Criteria:

- Oncological pathology still active or relapse

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Causes and factors that influence the low rate of reimplantation of ovarian tissue Time Frame: At least 5 years after surgery at first follow-up	Investigate the causes and factors that influence the low rate of reimplantation of ovarian tissue after the phase of collection and cryopreservation	At least 5 years after surgery at first follow-up
Early ovarian failure Time Frame: At least 5 years after surgery at first follow-up	Effects of early ovarian failure in this category of women, particularly in terms of bone metabolism (through Bone densitometry with a dual-energy x-ray absorptiometry, DEXA, Z-score. BMD:> -2.0 normal; ≤ -2.0:osteoporosi	At least 5 years after surgery at first follow-up
Early ovarian failure Time Frame: At least 5 years after surgery at first follow-up	Effects of early ovarian failure in this category of women, particularly in terms of cardiovascular risk (through ACC/AHA Cardiovascular Risk Calculator, %: <5%: low risk; 5-7.4%: Borderline risk; 7.5-19.9%: intermediate risk; ≥20%: high risk)	At least 5 years after surgery at first follow-up
Early ovarian failure Time Frame: At least 5 years after surgery at first follow-up	Effects of early ovarian failure in this category of women, particularly in terms of psychological function (through Short Form36 HealthSurvey (SF-36), score: 0-100	At least 5 years after surgery at first follow-up
Early ovarian failure Time Frame: At least 5 years after surgery at first follow-up	Effects of early ovarian failure in this category of women, particularly in terms of Middlesex Hospital Questionnaire (MHQ), score: <23: normal; >= 23: abnormal	At least 5 years after surgery at first follow-up
Early ovarian failure Time Frame: At least 5 years after surgery at first follow-up	Effects of early ovarian failure in this category of women, particularly in terms of psychological function through Beck's Depression Inventory, score: 0-63	At least 5 years after surgery at first follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Investigators

Principal Investigator: Renato Seracchioli, MD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 12, 2021

Primary Completion (Estimated)

December 31, 2030

Study Completion (Estimated)

December 30, 2031

Study Registration Dates

First Submitted

November 28, 2024

First Submitted That Met QC Criteria

February 14, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)