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Authors’ Response: FSH Receptor Polymorphism and Iatrogenic Ovarian Hyperstimulation

Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (C.D., G.S., V.D.M., S.C., G.V.), and Laboratory of Research on Human Reproduction (Y.E., A.D.), Faculté de Médecine, Université Libre de Bruxelles; Fertility Clinic (Y.E., A.D.) and Medical Genetics Department (G.S., G.V.), Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium

Address correspondence to: Anne Delbaere, M.D., Clinique de Fertilité, Hôpital Erasme, 808, Route de Lennik, B-1070 Brussels, Belgium. E-mail: adelbaer{at}ulb.ac.be.

To the editor:

We appreciated the letter by d’Alva et al. (1) concerning our article about FSH receptor (FSHr) polymorphisms and iatrogenic ovarian hyperstimulation syndrome (OHSS) (2). In this letter, they combine their data (n = 29) with ours (n = 37) to analyze a larger series of OHSS. The analysis of the combined data corroborates our previous conclusions that the FSHr genotype cannot predict OHSS but that the N⁶⁸⁰ allele could predict the severity of OHSS symptoms. However, in contrast with our previous findings, the authors do not show any difference regarding allele and genotype frequencies for S⁶⁸⁰N polymorphism between OHSS patients and a general female control population. We observed indeed a significant difference in the S⁶⁸⁰N polymorphism between the in vitro fertilization (IVF) population (IVF control group or OHSS group) and a Caucasian control group with an enrichment in the S⁶⁸⁰ allele in the IVF population (2). This could be related to the inclusion of patients presenting ovulatory disorders in the IVF population (2, 3, 4).

Importantly, we are afraid that the statistical analysis of the authors is not accurate for this point: in our hands, the analysis of the combined data still shows a significant difference in the distribution of the S⁶⁸⁰N alleles of the FSHr between the OHSS patients and the general population (P = 0.046 by ² test) confirming our previous conclusions. Regarding the frequencies of the genotype at position 680, the difference between the OHSS patients and the general population did not reach statistical significance (P = 0.135). Allele and genotype frequencies for S⁶⁸⁰N polymorphism were similar in OHSS patients and IVF controls (P = 1), as previously reported (2).

Furthermore, the interpretation of the combined data should be viewed with caution. Firstly, populations have a different ethnic origin, and the distribution of the allelic variants of the FSHr can vary among different populations (5). Moreover, d’Alva et al. (1) add only moderate and severe forms of OHSS, whereas in our series, mild forms had the highest enrichment in the S⁶⁸⁰ allele (2).

Before definitive conclusions can be drawn on the association of the FSHr S⁶⁸⁰N polymorphism and OHSS, it is necessary to analyze a larger series of patients presenting mild, moderate, and severe forms of the syndrome, which will probably only be obtained through a multicentric study. Therefore, we think that there is insufficient evidence today to justify a systematic screening of the N⁶⁸⁰ allele of the FSHr for all patients before ovarian stimulation for IVF.

Received April 19, 2005.

References

1. d’Alva CB, Serafini P, Motta E, Latronico AC, Mendonca BB 2005 Letter re: FSH receptor polymorphisms and iatrogenic ovarian hyperstimulation. J Clin Endocrinol Metab 90:4978 (Letter)[Free Full Text]
2. Daelemans C, Smits G, De Maertelaer V, Costagliola S, Englert Y, Vassart G, Delbaere A 2004 Prediction of severity of symptoms in iatrogenic ovarian hyperstimulation syndrome by follicle-stimulating hormone receptor Ser⁶⁸⁰Asn polymorphism. J Clin Endocrinol Metab 89:6310–6315[Abstract/Free Full Text]
3. Sudo S, Kudo M, Wada S, Sato O, Hsueh AJ, Fujimoto S 2002 Genetic and functional analyses of polymorphisms in the human FSH receptor gene. Mol Hum Reprod 8:893–899[Abstract/Free Full Text]
4. Laven JS, Mulders AG, Suryandari DA, Gromoll J, Nieschlag E, Fauser BC, Simoni M 2003 Follicle-stimulating hormone receptor polymorphisms in women with normogonadotropic anovulatory infertility. Fertil Steril 80:986–992[CrossRef][Medline]
5. Simoni M, Nieschlag E, Gromoll J 2002 Isoforms and single nucleotide polymorphisms of the FSH receptor gene: implications for human reproduction. Hum Reprod Update 8:413–421[Abstract/Free Full Text]

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				C. Daelemans, G. Smits, V. De Maertelaer, S. Costagliola, Y. Englert, G. Vassart, and A. Delbaere Authors' Response: FSH Receptor Polymorphism and Iatrogenic Ovarian Hyperstimulation J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4978 - 4979. [Full Text] [PDF]

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