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The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 8 4978
Copyright © 2005 by The Endocrine Society

Letter to the Editor

Letter re: FSH Receptor Polymorphisms and Iatrogenic Ovarian Hyperstimulation

Catarina Brasil d’Alva, Paulo Serafini, Eduardo Motta, Ana Claudia Latronico and Berenice Bilharinho Mendonca

Unidade de Endocrinologia do Desenvolvimento (C.B.d., A.C.L., B.B.M.), Laboratório de Hormônios e Genética Molecular LIM/42, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo; and Huntington Centro de Medicina Reprodutiva (P.S., E.M.), 05403-900 São Paulo, Brasil

Address correspondence to: Berenice B. Mendonca, Hospital das Clínicas, Laboratório de Hormônios e Genética Molecular LIM/42, Av. Dr. Enéas de Carvalho Aguiar, 155, 2° andar, Bloco 6, CEP 05403–900, São Paulo-SP, Brasil. E-mail: cbdalva{at}terra.com.br; beremen{at}usp.br.

To the editor:

We read the manuscript by Daelemans et al. (1), which demonstrated that the S680 allele of FSH receptor (FSHR) cannot predict the development of iatrogenic ovarian hyperstimulation syndrome (OHSS) in European patients, although the N680 allele can be a predictor of the severity of symptoms.

We recently analyzed the same FSHR polymorphism in 29 unrelated Brazilian women with OHSS after ovarian stimulation for in vitro fertilization (IVF) and in 50 fertile women. Thirteen patients had moderate OHSS, whereas 16 had severe OHSS. We found no differences regarding allele and genotype frequencies (P = 0.97 and P = 0.58, respectively) for S680N polymorphism between patients and controls (2).

Because Brazilian and European patients with OHSS were classified according to the same severity criteria and were submitted to similar ovarian stimulation protocols, we combined the results of Daelemans’ study (1) and ours (3). The studied group consisted of 66 women with iatrogenic OHSS (11 mild, 26 moderate, 29 severe), 130 European Caucasian females without OHSS after IVF, and 149 European and Brazilian females from the general population. The allele and genotype frequencies were analyzed through {chi}2 tests and revealed no differences either between OHSS patients and the general population or between OHSS patients and IVF controls (Table 1Go). These findings, therefore, confirm that the FSHR genotype cannot predict iatrogenic OHSS.


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  		TABLE 1. Allele and genotype frequencies for codon 680 of FSHR in OHSS patients, Brazilian and European general female population, and IVF controls

 
However, the comparison of allele frequencies among mild, moderate, and severe OHSS revealed a statistically significant difference due to a deficiency of the N680 allele in the mild OHSS group (P = 0.042) compared with the S680 allele (Haberman’s test). To perform an odds ratio analysis, we agglutinated the OHSS moderate and severe classes into a single one. The analysis of the 2x2 contingency table thus rearranged showed a statistically significant difference (P = 0.024), once again due to a deficiency of the N680 allele in the mild group and an odds ratio of 3.08 (95% confidence interval, 1.12–8.47) that might indicate that the N680 is associated with moderate and severe forms. No statistically significant difference was found in genotype distribution among mildly, moderately, and severely affected patients (Table 1Go).

In conclusion, analyzing a larger number of patients, we confirm that FSHR genotypes cannot predict the iatrogenic OHSS. On the other hand, these data indicate that the N680 allele can predict the severity of symptoms. Therefore, the N680 allele of FSHR is important in gonadotropin pharmacogenetics and should be screened in patients before ovarian stimulation treatments to avoid potential life-threatening complications.

Received March 23, 2005.

References

  1. Daelemans C, Smits G, 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]
  2. d’Alva CB, Serafini P, Motta E, Kohek MBF, Latronico AC, Mendonca BB 2005 Absence of follicle-stimulating hormone receptor activating mutations in women with iatrogenic ovarian hyperstimulation syndrome. Fertil Steril 83:1695–1699[CrossRef][Medline]
  3. Golan A, Ron-el R, Herman A, Soffer Y, Weinraub Z, Caspi E 1989 Ovarian hyperstimulation syndrome: an update review. Obstet Gynecol Surv 44:430–440[Medline]




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