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Authors’ Response: Ovarian Function in an Adult Woman with McCune-Albright Syndrome

Division of Reproductive Medicine, Department of Obstetrics and Gynecology, Erasmus Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands

Address correspondence to: Joop S. E. Laven, Ph.D., Division of Reproductive Medicine, Department of Obstetrics and Gynecology, Erasmus Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. E-mail: . laven{at}gyna.azr.nl

To the editor:

We thank Dr. Blumenfeld for his interest in our study and are grateful for the opportunity to respond to the important points raised in his letter.

With respect to the alternative approach of follicle aspiration and subsequent in vitro maturation as proposed by Blumenfeld, we would stress the following. In addition to the development of multiple preovulatory follicles, resulting from augmented FSH receptor signaling, premature luteinization is also to be anticipated in this patient due to increased LH receptor signal transduction. This latter phenomenon is comparable to a premature rise in serum LH as observed during initial protocols for ovarian hyperstimulation for in vitro fertilization (IVF) without GnRH agonist co-treatment. Protocols that exclude agonist treatment are associated with reduced IVF pregnancy rates due to premature luteinization of granulosa cells (1). Moreover, oocyte quality may be compromised by premature exposure to high LH levels, resulting in a reduced capacity for fertilization (either in vivo or in vitro) and the generation of viable embryos. We, therefore, believe that oocytes retrieved from these follicles are not suitable for in vitro maturation and subsequent IVF or intracytoplasmatic sperm injection. Because no firm clinical data are available, this or any other contention remains speculative.

We do share Blumenfeld’s concerns regarding unilateral ovariectomy in a young woman. It may be hypothesized that the healthy unaffected ovary can be differentiated from the affected ovary by GnRH analog suppresion of endogenous gonadotropin release. In case one ovary is rendered quiescent by such a treatment, removal of the ovary with continued activity might be the only way to restore normal fertility in these patients.

Finally, we agree with Blumenfeld that surrogacy, although not available in every country and particularly not for this indication, constitutes a potential treatment option in these rare patients. Despite mosaicism, also present in the uterus, endometrial receptivity in this patient may be restored (either partially or completely) after normalization of the steroid endocrine profile by removal of the abnormal ovary. Further evidence to support the concept of normal uterine function comes from reports concerning spontaneous pregnancies in McCune-Albright patients (2, 3).

Received November 28, 2001.

References

1. Devroey P 1999 Different treatment protocols for different indications. In: Shoham Z, Howles C, Jacobs HS, eds. Female infertility therapy. London: Martin Dunitz Ltd.; 215–220
2. Lee PA, Van Dop C, Migeon CJ 1986 McCune-Albright syndrome. Long-term follow-up. JAMA 256:2980–2984[Abstract/Free Full Text]
3. Malchoff CD, Reardon G, MacGillivray DC, Yamase H, Rogol AD, Malchoff DM 1994 An unusual presentation of McCune-Albright syndrome confirmed by an activating mutation of the Gs -subunit from a bone lesion. J Clin Endocrinol Metab 78:803–806[Abstract]

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