Pp1217-jarg-487526.tex

Journal of Assisted Reproduction and Genetics Journal of Assisted Reproduction and Genetics, Vol. 21, No. 3, March 2004 ( C 2004) Pregnancy and Delivery After Stimulation with rFSH
of a Galatosemia Patient Suffering Hypergonadotropic
Hypogonadism: Case Report
Yves Menezo, JR,1,3 Maryse Lescaille,1 Bernard Nicollet,1 and Edouard J. Servy2
Submitted July 30, 2003; accepted February 27, 2004 Purpose : To determine if hypergonadotropic hypogonadism related to galactosemia could be
linked to anomaly of the circulating FSH. A 26-year ONL
1-phosphate uridyltransferase) had a premature ovarian failure with amenorrhea since the
age of 19. The circulating level for FSH was 83 and 34 mU/mL for LH.
Methods : After treatment with a hormonal substitution cycle including estradiol and proges-
terone, the patient underwent stimulations with recombinant FSH. The first cycle, one 16-mm
diameter follicle and the second cycle one follicle of 17.5 mm of diameter were obtained at
the time of ovulation induction.
Results : The patient conceived and delivered a female baby weighting 3.38 kg after the second
stimulation protocol.
Conclusions : The impact of galactosemia on the ovary seems rather related to the absence
of recognition of circulating FSH by its receptor and not to a toxic alteration of the ovary by
itself as it is currently reported. The rFSH treatment following hormonal substitution cycles
allows to overcome infertility problems.
KEY WORDS: Galactosemia; hypergonadotropic hypogonadism; ovarian stimulation; rFSH.
INTRODUCTION
progesterone are used to assist pubertal changes andto prevent sequelae of early postmenauposal state PROOFREADING
(6,7). In human gonadotropins, carbohydrate struc- lated to the deficiency of one of three different en- ture is related to bioactivity (8,9). More precisely, the zymes in the metabolism of galactose: galactokinase follitropin beta chain shows N-acetyllactosamine re- (GALK), galactoso-1-phosphate uridyltransferase peats. On this basis, we postulated that an aberrant (GALT), the FOR
biologically inactive form of FSH, preventing a nor- epimerase (GALE). It has been generally admitted mal ligand-receptor binding and a proper recognition that galactose and its metabolites could be toxic to the of the circulating FSH was produced.
ovary (1-2). This generally leads to more or less se-vere hypergonadotropic hypogonadism. Women withgalactosemia have a high incidence of ovarian failures CASE REPORT
and childbearing is rather rare (3,4), even if spon-taneous in some cases (5). Exogenous estrogen and VB a 26-year-old Caucasian patient had regular menses up to 19 years of age. She was carrying theGALT-type galactosemia and was submitted to hor- 1 IRH/Laboratoire Marcel Merieux, Bron, France.
monal substitutive treatment including estradiol and 2 The Servy Institute, Augusta, Georgia.
3 To whom correspondence should be addressed; e-mail: ymenezo@ progesterone. She came for ART counselling after having stopped her hormonal substitution treatment 1058-0468/04/0300-0089/0 C 2004 Plenum Publishing Corporation Journal of Assisted Reproduction and Genetics Menezo, Lescaille, Nicollet, and Servy
for 6 months. Her biological parameters were: a cir- the receptor. The generally admitted direct toxic ef- culating FSH at 83 and LH was 34 IU/L, Estra- fect on the ovary, (1-7) does not fit with our observa- diol 14 pg/mL. Her TSH was within normal range: tion. Galactosemia negatively modulates the biologi- 1.6 mU/L. We advised the couple to undergo ovarian cal activity of FSH (10), more than probably through stimulations with rFSH. Husband sperm is of good a modification of the sugar moeity. Circulating FSH quality (114 millions/mL, 5 mL, 85% living cells, 2/3 is recognized by the radioimmunoassay but not by high quality motility, 33% abnormal forms according the receptor. We are currently investigating the struc- to WHO criteria). We chose rFSH as it allows a "pure" tural modifications of her FSH. In conclusion, the use of rFSH treatment offers new hopes for galactosemia The patient was stimulated twice. She was submit- patients, submitted to premature ovarian failure, to ted first to an artificial cycle treatment (hormone re- placement therapy) including Estradiol (2 tablets ofEstradiol 17 beta: Provames 2 mg) followed by dy-drogesterone (Duphaston 20-mg intravaginally) dur- REFERENCES
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the absence of recognition of the circulating FSH by Journal of Assisted Reproduction and Genetics, Vol. 21, No. 3, March 2004

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