Elsevier

The Lancet

Volume 364, Issue 9443, 16–22 October 2004, Pages 1405-1410
The Lancet

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Livebirth after orthotopic transplantation of cryopreserved ovarian tissue

https://doi.org/10.1016/S0140-6736(04)17222-XGet rights and content

Summary

Background

The lifesaving treatment endured by cancer patients leads, in many women, to early menopause and subsequent infertility. In clinical situations for which chemotherapy needs to be started, ovarian tissue cryopreservation looks to be a promising option to restore fertility. In 1997, biopsy samples of ovarian cortex were taken from a woman with stage IV Hodgkin's lymphoma and cryopreserved before chemotherapy was initiated. After her cancer treatment, the patient had premature ovarian failure.

Methods

In 2003, after freeze-thawing, orthotopic autotransplantation of ovarian cortical tissue was done by laparoscopy.

Findings

5 months after reimplantation, basal body temperature, menstrual cycles, vaginal ultrasonography, and hormone concentrations indicated recovery of regular ovulatory cycles. Laparoscopy at 5 months confirmed the ultrasonographic data and showed the presence of a follicle at the site of reimplantation, clearly situated outside the ovaries, both of which appeared atrophic. From 5 to 9 months, the patient had menstrual bleeding and development of a follicle or corpus luteum with every cycle. 11 months after reimplantation, human chorionic gonadotrophin concentrations and vaginal echography confirmed a viable intrauterine pregnancy, which has resulted in a livebirth.

Interpretation

We have described a livebirth after orthotopic autotransplantation of cryopreserved ovarian tissue. Our findings suggest that cryopreservation of ovarian tissue should be offered to all young women diagnosed with cancer.

Published online September 24, 2004 http://image.thelancet.com/extras/04art9230web.pdf

Introduction

Treatment of childhood malignant disease is becoming increasingly effective. Aggressive chemotherapy and radiotherapy, and bone-marrow transplantation, can cure more than 90% of girls and young women affected by such disorders. However, the ovaries are very sensitive to cytotoxic treatment, especially to alkylating agents and ionising radiation, generally resulting in loss of both endocrine and reproductive function.1 Moreover, uterine irradiation at a young age reduces adult uterine volume.2

By 2010, about one in 250 people in the adult population will be childhood cancer survivors.3 Several potential options are available to preserve fertility in patients facing premature ovarian failure, including immature and mature oocyte cryopreservation, and embryo cryopreservation.4, 5 For patients who need immediate chemotherapy cryopreservation of ovarian tissue is a possible alternative.4, 6, 7 The aim of this strategy is to reimplant ovarian tissue into the pelvic cavity (orthotopic site) or a heterotopic site like the forearm once treatment is completed and the patient is disease-free.4, 8, 9, 10, 11, 12

Oktay and colleagues have reported laparoscopic transplantation of frozen-thawed ovarian tissue to the pelvic side wall,8 forearm,9 and beneath the skin of the abdomen. A four-cell embryo was obtained from 20 oocytes retrieved from tissue transplanted to the abdomen, but no pregnancy happened after transfer.13 Radford and colleagues12 reported a patient with a history of Hodgkin's disease treated by chemotherapy, in whom ovarian tissue had been biopsied and cryopreserved 4 years after chemotherapy and later reimplanted. In this case, histological section of ovarian cortical tissue revealed only a few primordial follicles because of the previous chemotherapy. After reimplantation, the patient had only one menstrual period. In 2004, a livebirth after a fresh ovarian tissue transplant in a primate was reported.14

In 1995, the Catholic University of Louvain ethics committee approved a protocol to assess the safety and efficacy of cryopreservation of ovarian tissue in women treated with high doses of chemotherapy, which could induce ovarian failure. So far, 146 patients have undergone cryopreservation of ovarian tissue in our department before starting chemotherapy and two patients have undergone reimplantation (one in August, 2004).

Here, we describe the outcome of orthotopic autotransplantation of cryopreserved ovarian tissue in a patient from whom tissue was obtained and frozen before chemotherapy was initiated for Hodgkin's lymphoma.

Section snippets

Patient

In 1997, a 25-year-old woman presented with clinical stage IV Hodgkin's lymphoma. Ovarian tissue cryopreservation was undertaken before chemotherapy. We obtained written informed consent. By laparoscopy, we took five biopsy samples—about 12–15 mm long and 5 mm wide—from the left ovary. Removal of the whole ovary was not an option because one can never completely exclude recovery of ovarian function after chemotherapy. Indeed, premature ovarian failure after chemotherapy is dependent on age,

Results

Vital fluorescent staining confirmed survival of all primordial follicles after freeze thawing. By contrast, no primordial follicles were noted in serial sections of the four biopsy samples taken from either of the atrophic ovaries at the second or third laparoscopy. Follicular density was between 4 and 5 follicles per μL.

After the first transplantation, LH and FSH concentrations fell again (figure 2). Vaginal echography then confirmed the presence of a corpus luteum on the left ovary. LH and

Discussion

We report a livebirth after successful orthotopic transplantation of cryopreserved ovarian tissue in a woman with stage IVab Hodgkin's lymphoma.

Unfortunately, in most female cancer patients, aggressive chemotherapy and radiotherapy leads to ovarian failure. Restoration of ovarian function after chemotherapy or radiotherapy has two main goals: to improve quality of life and restore reproductive function. For patients who need immediate chemotherapy, ovarian tissue cryopreservation, undertaken

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