Serono Ltd, Bedfont Cross, Stanwell Road, Middlesex TW14 8NX, UK e-mail: amir.lass{at}serono.com
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Abstract |
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Key words: cancer/ovarian biopsy/ovarian reserve/primordial follicles
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Introduction |
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Ovarian biopsy as integral part of infertility evaluation |
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Regretfully, the predictive power of all these tests alone or in combination is quite limited. This lack of sufficient and adequate tests to predict the ovarian reserve led our team to suggest a novel method of quantifying the number of small follicles in ovarian biopsies from infertile patients (Lass et al., 1997b). The promising results of negative correlation between a patients age and follicular density and less follicles in unexplained infertility compared with tubal infertility led me to suggest considering ovarian biopsy as a diagnostic tool quite early in infertility investigation (Lass, 2001
).
We were quite aware of major limitations of ovarian biopsy in this context. (i) This is an invasive procedure which, although performed during diagnostic laparoscopy, might cause future adhesions, decrease the ovarian reserve further and lengthen the time of operation under anaesthesia. (ii) Whether the biopsy(ies) is/are a true reflection of the follicular distribution in the ovarian cortex, a factor never investigated until then. Blocks initial histopathological studies did not address this question (Block, 1952). Randomized or blind single biopsy is adequate if follicles are evenly spread in the ovarian cortex (in any case, they are not deeper than 2 mm from the surface; Lass et al., 1997b
) This uncertainty triggered my call for further research to study the natural distribution of primordial follicles in the ovarian cortex and their dynamics through reproductive age up to the menopause (Lass, 2001
). (iii) The quantitative counting of primary follicles does not provide any information about the quality of the oocytes embedded in them.
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Ovarian biopsies for cancer patients |
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The distribution of follicles in the ovarian cortex |
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Recently the challenge to study the natural distribution of primordial follicles in the ovarian cortex and their dynamics through reproductive age up to the menopause has been picked up by a few investigators. Qu et al. (2000) examined ovarian biopsies from 24 patients who underwent infertility evaluation. The distribution of follicles was extremely uneven in ovarian tissue. A large variation in follicle numbers was observed in ovarian tissue samples from patient to patient. Furthermore, even though some tissue samples were originally obtained from the same patient, the number of follicles counted in one sample of ovarian tissue did not match the number found in another tissue sample.
Kohl et al. (2000) compared samples of controlateral ovaries from five women and multiple biopsies from different sites in another two patients, all of them from women having diagnostic laparoscopy for infertility. They found large variation between the ovaries and between the sites of the biopsies.
Poirot et al. (2002) collected ovarian tissue from 31 patients having chemotherapy. They evaluated at least 10 serial sections per patient (range 1015) and found that follicles were not homogeneously distributed within the ovarian cortex.
Recently, Schmidt et al. (2003), in very methodological and laborious research, showed in 21 patients with malignant disease a wide variation in follicular density from 1.1 to 190.6 follicles/mm3 between the patients and again with significant inverse correlation between follicular density and age.
However, the new information from this work is the evaluation of whole ovary in three patients. In each ovary, numerous pieces of cortex were isolated, and the histological evaluation revealed a wide variation in the number of primordial follicles between each fragment of the same ovary. In all four studies, a significant negative correlation between follicular density and age has been established.
Although only three whole ovaries were studied, the combined results of this study and the previous ones mentioned above led the author to the conclusion that the ovarian cortex indeed varies significantly in its follicular content. There is no good explanation for the cause of this variation nor is it clear whether a specific area is more favourable for follicular nesting than another or if it is due to purely random allocation.
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Conclusions |
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Young girls and women who are undergoing ovarian biopsy collection as a fertility preservation measure before chemotherapy in malignant diseases are expected to have normal follicular distribution according to their age. However, every effort should be made to assess the follicular quantity in real time by frozen section and, if impossible or impractical, to attempt multiple biopsies from different sites of the ovaries, to ensure that the frozen pieces of ovarian tissue have a sufficient number of follicles.
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References |
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Submitted on July 16, 2003; resubmitted on September 9, 2003; accepted on November 4, 2003.