Ovarian Tissue Transplantation: A Comprehensive Guide for Patients

Table of Contents

• Introduction: Preserving Fertility Against the Clock
• How the Research Was Conducted
• Patient Profiles: Who Undergoes This Procedure
• Transplantation Methods and Success Rates
• Spontaneous Conception vs. IVF Outcomes
• The Significant Impact of Pelvic Radiation
• How Chemotherapy Affects Success Rates
• Safety: Very Low Risk of Cancer Returning
• What This Means for Patients
• Study Limitations and Future Research
• Patient Recommendations and Considerations
• Source Information

Introduction: Preserving Fertility Against the Clock

For women facing cancer treatments that threaten their fertility, ovarian tissue cryopreservation (freezing) and transplantation offers a powerful option to potentially have children later. This technique involves removing and freezing ovarian tissue before chemotherapy or radiation, then reimplanting it after treatment when the patient is ready to conceive.

While over 7,800 women have undergone ovarian tissue freezing across these five European centers, actual transplantation experience remains more limited. This review combines data from 285 women who underwent ovarian tissue transplantation, providing the most comprehensive picture to date of what patients can realistically expect from this emerging technology.

The research focuses on several critical patient concerns: which surgical techniques work best, success rates for natural conception versus IVF, how previous chemotherapy affects outcomes, the significant impact of pelvic radiation, and most importantly—the very low risk of cancer returning through transplanted tissue.

How the Research Was Conducted

Researchers from five leading European fertility centers collaborated to pool their extensive experience with ovarian tissue transplantation. The centers included teams from Denmark (62 patients), Spain (53 patients), Belgium (29 patients), France (53 patients), and the FertiPROTEKT network across Germany, Switzerland and Austria (88 patients).

The study analyzed all available data on patient characteristics, freezing and transplantation procedures, and most importantly—pregnancy and live birth outcomes. The researchers conducted a thorough literature review of all peer-reviewed publications on ovarian tissue transplantation to ensure their findings reflected the current state of knowledge in this field.

This collaborative approach allowed for analysis of a significantly larger patient group than any single center could provide, giving more reliable statistics about success rates, complications, and factors that influence outcomes. The team examined detailed information about each patient's cancer type, treatment history, age at freezing, age at transplantation, and subsequent fertility outcomes.

Patient Profiles: Who Undergoes This Procedure

The 285 women in this study represented a diverse group of patients seeking to preserve their fertility against various medical threats. The vast majority (88.7%) had malignant diseases, while 11.3% had non-malignant conditions that still threatened their fertility.

Among cancer patients, the most common diagnoses were:

• Hematologic cancers (37.2% of malignant cases): Hodgkin's lymphoma (24.6%), non-Hodgkin's lymphoma (11.2%), and leukemia (1.4%)
• Breast cancer (33.3% of malignant cases)
• Various other cancers including digestive tract cancers, cervical cancer, borderline ovarian tumors, and Ewing sarcoma

For non-malignant conditions, the most common were hemoglobinopathies (3.1% of all patients), autoimmune diseases (3.1%), and aplastic anemia (1.7%). The average age was 29.3 years at the time of tissue freezing and 34.6 years at the time of first transplantation.

Most patients (81.2%) had already experienced premature ovarian insufficiency (early menopause) before transplantation, while 18.8% still had irregular periods but showed evidence of infertility—often after failed IVF attempts. Fifty-nine patients underwent a second transplantation and 7 had a third procedure, indicating that multiple attempts are sometimes necessary.

Transplantation Methods and Success Rates

Researchers compared different surgical approaches for reimplanting frozen ovarian tissue. The overwhelming majority (97.5%) of patients received orthotopic transplantation—returning tissue to the pelvic area where ovaries normally reside. Only 5 patients received only heterotopic transplantation (outside the pelvic cavity, such as in the forearm or abdominal wall), while 3 patients received both types.

Among orthotopic procedures, the specific techniques included:

• 16.7% grafted to the exposed medulla of decorticated ovaries
• 62.7% grafted to a newly created peritoneal window
• 20.4% grafted to both the ovarian medulla and peritoneal window

The live birth rates were remarkably similar across these orthotopic approaches: 30.5% with transplantation to the ovary, 34.8% to the peritoneum, and 34% with the combined technique. Critically, no successful pregnancies resulted from heterotopic grafts, clearly establishing that returning tissue to the pelvic area produces superior results.

Overall, 26% of the 285 women successfully gave birth to one or more healthy babies—resulting in 95 newborns total. Eight women gave birth to more than one child through this procedure. The success rate was slightly higher in women who still had some ovarian function before transplantation (30.6%) compared to those who had complete premature ovarian insufficiency (25.4%), but this difference wasn't statistically significant.

Spontaneous Conception vs. IVF Outcomes

The study revealed striking differences between natural conception and IVF outcomes following ovarian tissue transplantation. The conception rate was similar (40% natural vs. 36% IVF), but live birth rates were higher with natural conception (30% vs. 21%) while miscarriage rates were lower (10% vs. 18%).

Women who successfully became pregnant were significantly younger at the time of tissue freezing—average 26.9 years compared to 29.8 years for those who didn't achieve pregnancy. This age difference was particularly pronounced in the IVF group, where the upper age limit for successful childbirth was 33 years at freezing.

The IVF results revealed several challenges:

• Only 50% of IVF patients actually underwent embryo transfer despite multiple stimulation attempts
• 31% of follicles were empty (contained no oocyte) during retrieval
• Only 32% of retrieved oocytes developed into viable embryos
• 37% of pregnancies ended in miscarriage among those who achieved embryo transfer

These numbers reflect the dramatically reduced ovarian reserve that women have after transplantation. Even under ideal conditions, patients might only have 5-8% of their original ovarian tissue function restored. This explains why these women are considered "poor responders" to fertility treatments from the outset.

The Significant Impact of Pelvic Radiation

Pelvic radiation dramatically affects transplantation success rates. Among the 36 women (12.6% of the study group) who received pelvic radiation before transplantation, success varied considerably based on radiation dose and cancer type.

Women with anal or cervical cancer (15 patients) who typically receive high-dose radiation had no successful live births. Those with colorectal cancer (8 patients) who receive reduced radiation doses had a 12.5% success rate. Patients with systemic diseases like lymphoma or leukemia who received total body irradiation (with lower pelvic doses) had the best outcomes at 50% success.

The reasons for reduced success after high-dose radiation include:

• Fibrosis (scarring) of pelvic tissues reducing blood supply to transplants
• Potential damage to the uterus affecting its ability to support pregnancy
• General tissue damage throughout the pelvic region

Research shows that radiation doses above 2.5 Gy to the pelvis/abdomen increase risks of preterm birth and low birth weight infants. Doses above 5 Gy to the uterus create significantly higher risks—6.8 times more likely to have low birth weight babies and 3.5 times more likely to deliver prematurely.

How Chemotherapy Affects Success Rates

Unlike radiation, chemotherapy before tissue freezing does not necessarily impair transplantation success, depending on the specific drugs used and total dosage received. The study found that chemotherapy administered before tissue freezing didn't prevent successful pregnancies afterward.

Certain chemotherapy drugs are more damaging to ovaries than others. Alkylating agents, particularly cyclophosphamide, cause the most damage to resting follicles in a dose-dependent manner. This means higher cumulative doses cause more ovarian damage, but the tissue that survives freezing and transplantation can still function effectively.

The research emphasizes that success depends on careful patient selection. The ideal candidates are women under 35 years (when ovarian reserve is still relatively high), those with at least a 50% risk of premature ovarian insufficiency from their treatment, and patients with a realistic chance of 5-year survival from their underlying condition.

Safety: Very Low Risk of Cancer Returning

One of the most important findings for patients is the very low risk of cancer recurrence due to reimplanting frozen tissue. According to current data, the risk appears minimal, which should provide significant reassurance to women considering this procedure.

This safety record is particularly remarkable given that 37.2% of patients had hematologic cancers (like leukemia and lymphoma), which theoretically could have cancer cells present in ovarian tissue. The rigorous screening and safety protocols developed by these leading centers have effectively minimized this risk.

The excellent safety profile makes ovarian tissue transplantation a viable option even for patients with blood cancers, who previously might have been excluded from fertility preservation approaches that involve reimplanting tissue.

What This Means for Patients

This large collaborative study provides several important insights for patients considering fertility preservation:

First, ovarian tissue transplantation has moved from experimental to established practice in leading European centers, with predictable success rates. The 26% overall live birth rate represents a substantial achievement for women who would otherwise have no chance of biological children.

Second, the procedure successfully restores ovarian function in nearly all women, with endocrine function resuming typically within 4-5 months after transplantation. This means natural menstrual cycles resume, providing both fertility potential and natural hormone production.

Third, spontaneous conception produces better outcomes than IVF, suggesting that patients should allow time for natural conception before immediately pursuing fertility treatments. The body's natural selection processes appear better at identifying viable eggs than current IVF protocols in these patients.

Finally, the procedure is remarkably safe regarding cancer recurrence risk, making it appropriate for even patients with blood cancers who might have microscopic cancer cells in their tissue.

Study Limitations and Future Research

While this study represents the largest pooled experience with ovarian tissue transplantation, several limitations should be acknowledged. The data come from five advanced European centers with extensive experience, so results might not generalize to all medical facilities.

The study also represents early experience with this technology. As techniques improve, success rates will likely increase beyond the current 26% live birth rate. The field is rapidly evolving, with ongoing research focusing on improving follicle survival during freezing and transplantation.

Additionally, long-term data on children born from transplanted tissue remains limited, though no abnormalities have been reported to date among the 95 babies born in this study group. Continued follow-up of these children is important.

Future research needs to address the poor IVF outcomes in these patients. Possible solutions include different stimulation protocols, better timing of retrieval, and improved support for the corpus luteum (which produces progesterone to sustain pregnancy).

Patient Recommendations and Considerations

Based on this comprehensive review, patients considering ovarian tissue transplantation should:

1. Freeze tissue as young as possible—success rates decline significantly after age 35, with little chance of success if frozen after age 40
2. Consider the impact of pelvic radiation—if high-dose pelvic radiation is planned, success rates are dramatically reduced, though not impossible
3. Attempt natural conception first—spontaneous pregnancy yields better outcomes than IVF in these patients
4. Understand the likely need for multiple cycles—many patients require more than one transplantation attempt to achieve success
5. Choose experienced centers—success rates vary considerably by center experience with these techniques

Patients should also recognize that while the procedure restores fertility, it doesn't extend the natural reproductive lifespan. Women who freeze tissue at 30 will effectively have the ovarian reserve of a 30-year-old when they transplant, but they'll still face age-related pregnancy complications if they wait until their late 30s or 40s to attempt conception.

Source Information

Original Article Title: Transplantation of cryopreserved ovarian tissue in a series of 285 women: a review of five leading European centers

Authors: Marie-Madeleine Dolmans, Michael von Wolff, Catherine Poirot, Cesar Diaz-Garcia, Luciana Cacciottola, Nicolas Boissel, Jana Liebenthron, Antonio Pellicer, Jacques Donnez, Claus Yding Andersen

Publication: Fertility and Sterility, Volume 115, Issue 5, May 2021, Pages 1102-1115

Note: This patient-friendly article is based on peer-reviewed research originally published in Fertility and Sterility, the official journal of the American Society for Reproductive Medicine. The information has been comprehensively translated for patient education while preserving all scientific findings, data, and conclusions from the original research.