Ovarian tissue transplantation: 10 years of experience at the Bologna University

Abstract

Objective: The efficiency of ovarian tissue transplantation (OTT) was established in terms of ovarian function recovery (95% of cases), number of live births (over 200 worldwide to date) and induction of puberty. Unfortunately, the lack of international registries and the fact that many centers have not yet reported their outcomes, lead to poor knowledge of the exact fertility data. The aim of the study is to describe our experience with OTT to restore ovarian function and fertility.

Methods: This study was designed as a single-center, observational, retrospective, cohort study that includes women who underwent OTT between December 2012 and June 2023 at our center. After approval by the oncologist/hematologist, a small fragment of ovarian tissue was thawed and analyzed to detect the presence of micrometastases before OTT. Thawed ovarian tissue was grafted laparoscopically at multiple sites, including the remaining ovary and pelvic side wall (orthotopic transplantation) and/or abdominal wall (heterotopic transplantation). After OTT, ovarian function was monitored by hormonal assay, ultrasound and color Doppler at approximately 4-week intervals.

Results: Between December 2012 and June 2023, 30 women performed OTT. Prior to OTT, immunohistochemical and molecular analyses revealed no micrometastases in all thawed ovarian tissue samples. In our series of 30 women, 20 of women were on premature ovarian insufficiency (POI), and the remaining ten cases still had oligomenorrhea and difficulty getting pregnant. Among the women with POI before OTT and at least 6 months follow-up, recovery of endocrine function was observed in all but one woman who underwent orthotopic transplantation (13 of 14 cases), in one out of two women who underwent both orthotopic and heterotopic transplantation (1 of 2 cases) and in all women who underwent heterotopic transplantation (4 of 4 cases). Women who underwent OTT to enhance fertility had no alterations in menstrual cycle and hormonal levels. In total, ten pregnancies were obtained in 25 women, resulting in four live births, two ongoing pregnancies and four spontaneous abortions.

Conclusion: Our data can help patients and physicians in their discussions and decisions about the need and possibilities of preserving fertility.

Keywords: cancer; fertility preservation; live births; longevity; orthotopic and heterotopic transplantation; ovarian tissue cryopreservation; pregnancies; restoration of endocrine function.

Figure 1

Pre-operative period flow chart. Follicle-stimulating Hormone (FSH), luteinizing hormone (LH), 17-hydroxyprogestrone (17-OHP), dehydroepiandrosterone sulfate (DEAH-S), thyrotropin (TSH), Anti-Mullerian Hormone (AMH), Hepatitis B surface antigen (HBs Ag), hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum (TPHA), human immunodeficiency virus (HIV), dual-energy-xray-absorptiometry (DEXA), positron emission tomography (PET), total-body computed tomography (Total body, CT).

Figure 2

Surgical techniques of orthotopic transplantation of cryopreserved ovarian tissue. (A, B) A longitudinal incision was made on the surface of ovaries and a pocket was developed in the ovarian parenchyma by blunt dissection. Cortical strips were sutured into the ovarian pocket and the same sutures were used to close the ovary. (A) Transplanted right ovary (3 samples with following sizes 1.5 cm × 4 mm × 1 mm); (B) Transplanted left ovary (2 samples with following sizes 1.2 cm × 3 mm × 1 mm). (C) An incision was made on the surface of the peritoneum near the ovarian vessels and fimbria. Cortical strips were inserted into the pocket and a 4-0 Vicryl suture were used to close the peritoneal pocket (2 samples with following sizes 1 cm × 4 mm × 1 mm).

Figure 3

Surgical techniques of heterotopic transplantation of cryopreserved ovarian tissue. Cortical strips (sample size: 1 cm × 4 mm × 1 mm) were placed in subcutaneous pockets created above the fascia muscularis in the suprapubic area and closed with a 4-0 Vicryl suture.

Figure 4

Patient’s specific immunohistochemical and molecular analyses performed on a small fragment of ovarian tissue to detect the presence of micrometastases. CAM-5.2: Cytokeratin; WT1: Wilms tumor-suppressor gene-1; Gab1: GRB2-associated-binding protein 1; Yap1: yes-associated protein 1; CK: creatinchinasi; TG: Thyroglobulin; TTF1: Thyroid transcription factor-1; PCR: Polymerase chain reaction.

Figure 5

Women who request OTT between December 2012 and June 2023 at our center.