Hum. Reprod. Advance Access originally published online on January 29, 2004
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Human Reproduction, Vol. 19, No. 3, 470-471,
March 2004
© 2004 European Society of Human Reproduction and Embryology
Assessment of ovarian reserve. Is there still a role for ovarian biopsy?
First do no harm!
1 Virginia Center for Reproductive Medicine, Reston, VA and 2 George Washington University, Washington, DC, 3 Reproductive Medicine Associates of New Jersey, Morristown, NJ, USA
To whom correspondence should be addressed at: 11150 Sunset Hills Road, Suite 100, Reston, VA 20190, USA. E-mail: RScott{at}rmanj.com
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Abstract |
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 Top Abstract IntroductionThe pattern of follicular...ConclusionReferences |
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Multiple endocrine, ultrasound-based and dynamic tests have been proposed for the assessment of ovarian reserve. Lately, ovarian biopsy has been proposed as a more representative functional test of ovarian reserve, and has been recommended as an early step in the investigation of infertility. Central to this hypothesis is the idea that a random biopsy of the ovarian cortex is reflective of the actual ovarian follicular pool. Recent studies have shown a wide variation in the number and distribution of ovarian follicles even from the same ovary and in the same patient. Coupled with the invasiveness of performing the biopsy and the risk of adhesion formation, we believe that there should not be a role for ovarian biopsy in ovarian reserve testing.
Key words: ovarian biopsy/ovarian reserve testing
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Introduction |
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TopAbstractIntroductionThe pattern of follicular...ConclusionReferences |
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Since the early days of infertility testing, investigations have centred on a predictive test for ovarian reserve. Multiple dynamic and endocrine tests, such as basal FSH and estradiol, FSH/LH ratio, clomiphene citrate challenge test (CCCT), inhibin-B levels, anti-Müllerian hormone levels, GnRH agonist stimulation test (GAST) and exogenous FSH ovarian reserve test (EFORT), have been proposed (Scott and Hofmann, 1995
; Sharara et al., 1998; Van Rooij et al., 2002; Kwee et al., 2003). Other non-invasive tests include ovarian volume, antral follicle count and Doppler ovarian stromal blood flow (Lass et al., 1997a; Tomas et al., 1997; Sharara and McClamrock, 1999; Engmann et al., 1999; Frattarelli et al., 2000). Recently, Lass proposed to evaluate the ovarian follicular pool directly by obtaining an ovarian biopsy to check the follicle count (Lass et al., 1997b; Lass, 2001). Central to this hypothesis is the homogeneous distribution of these follicles in the ovarian cortex. However, Lass wrote that the main limitation of this hypothesis was that the follicular density within the biopsy specimen may not accurately represent the density of follicles in the whole ovary, and he called for active investigation into ovarian follicular distribution among different women and in the same ovarian cortical sample (Lass, 2001). Recent reports confirmed Lass’ doubts and shed new and important information on the follicular distribution in the human ovary. |
The pattern of follicular distribution |
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TopAbstractIntroductionThe pattern of follicular...ConclusionReferences |
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Lass et al. (1997b
) evaluated 60 infertile women who underwent an ovarian biopsy by laparoscopy or laparotomy and found a significant inverse correlation between age and the number of follicles. Qu et al. (2000) heeded Lass’ call to investigate the follicular distribution further, and were the first to report on the follicular morphology and distribution from 24 women (age 21–41 years) undergoing an infertility investigation. The authors evaluated the morphology and distribution of primordial, primary and secondary follicles in both fresh and cryopreserved ovarian samples. They were surprised to find that the follicular distribution was extremely uneven, along with a large variation in follicular numbers from patient to patient, and from sample to sample from the same ovary (Qu et al., 2000). They also noted a decline in the follicular pool with age, confirming Lass’ findings (Lass et al., 1997b). Kohl et al. (2000) confirmed the above results in 37 ovarian biopsy samples from 29 women, showing a wide variation in follicular number even from biopsies from the same ovary, and between the left and right ovaries in five patients.
The recent interest in ovarian tissue cryopreservation for cancer patients has opened the doors for the further investigation of the follicular distribution in the ovarian cortex in young women interested in ovarian cryopreservation before or after chemotherapy. Poirot et al. (2002) collected ovarian tissue from 31 women (seven had half an ovary and 24 had a whole ovary removed), 19 of whom had between three and six courses of chemotherapy (13 had low doses of alkylating agents). They showed that the follicular distribution was again non-homogeneously distributed within the ovarian cortex and that the follicular pool declined with age. It was of interest that the investigators could not find a deleterious effect of prior chemotherapy on the mean follicular concentration (Poirot et al., 2002).
Most recently, Schmidt et al. (2003) consented 21 women with cancer (six of whom received prior chemotherapy) to have one or both ovaries cryopreserved; 17 had one ovary removed and four had ovarian biopsies. In addition, three of the 21 had both ovaries removed. For the first time, these investigators studied the follicular distribution in the whole ovarian cortex instead of a ‘representative’ section. Confirming prior results, the investigators showed a significant inverse relationship between age and follicular density. Among the three women who had both ovaries removed, there was a huge variation in the number of primordial follicles between each fragment of the same ovary of several orders of magnitude. In one example, two follicles were found in one fragment and >2000 in another fragment from the same ovary. It was of interest that in all three ovaries, the primordial follicles tended to lie in clusters in the ovarian fragments rather than being evenly distributed throughout the tissue (Schmidt et al., 2003).
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Conclusion |
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TopAbstractIntroductionThe pattern of follicular...ConclusionReferences |
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There is good evidence currently that the follicular distribution in the ovarian cortex is extremely heterogeneous, which implies that an ovarian biopsy sample is not representative of the actual follicular pool, and therefore this invasive (and potentially harmful) test is unlikely to add any new information to the ovarian reserve tests currently in practice. While recent investigations point to the use of the antral follicle count as the most predictive test of ovarian reserve (Frattarelli et al., 2000
; Bancsi et al., 2002), and a likely true reflection of the actual follicular pool (Morris et al., 2002; Scheffer et al., 2003), continued investigation in this critical area is warranted. |
References |
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