Atabekoğlu, Cem Somer

Baltacı, Volkan

Sönmezer, Murat

Özmen, Batuhan

Fertility and Sterility

English

Ufuk Universitesi Akademik Acikerisim Sistemi

LETTER TO THE EDITORDo patients with heterozygote mutations in GALT genehave increased risk for impaired reproductive functions?To the Editor:We read with great interest the case report by Gubbels et al.(1) indicating a pregnancy despite undetectable antimullerianhormone levels in a patient with classical galactosemia. Asimilar 22-year-old patient with compound heterozygotemutation for GALT gene (Duarte type) K285 N/N314D (2)presented to our clinic with a history of two blighted ova,a spontaneous pregnancy resulted in delivery and subsequentdeath of a galactosemic infant. The couple suffered from in-fertility for 3 years at admission to our infertility center. Oninitial evaluation day 3, FSH was 6.2 IU/mL, E2 was 20 pg/mL, and antral follicle count (AFC) was 8. Her husband,who had asthenozoospermia, had a heterozygous Q188Rmutation of GALT gene. The couple previously underwentinsemination cycles three times and one intracytoplasmicsperm injection (ICSI) cycle before admission to our unit.In that first ICSI cycle, a suboptimal ovarian response, withfour M2 and five immature oocytes, occurred after controlledovarian stimulation (COS) with 225 IU rFSH. notably, noneof the oocytes fertilized. In the subsequent cycle, preimplan-tation genetic diagnosis was scheduled owing to the previousgalactosemic infant delivery, recurrent pregnancy loss, andtotal fertilization failure (TFF). In the second ICSI cycle, atour clinic, five immature and three M2 oocytes were retrievedafter COS with 225 IU rFSH, and TFF occurred again. Withan aim to decrease the toxic effects of the high galactose onthe gonads, a galactose-free diet was recommended to thecouple for 4 months. In the third ICSI cycle, five M2 alongwith three immature oocytes were retrieved after COH with150 IU rFSH and 75 IU hMG. After combined use of piezoelectrical stimulation and ICSI, one grade B and two gradeC embryos could be generated. Despite poor quality, allembryos underwent blastomere biopsy, but none of theseembryos were found normal for GALT gene.It is still unclear whether infertility, ovarian failure, ordiminished ovarian reserve and subsequent poor obstetricoutcome are associated with nonclassical galactosemia.Patients with low erythrocyte GALT activity had a 14-foldincreased risk of menopause compared with those withnormal GALT activity. Cramer et al. (3) also describedsignificantly higher serum FSH levels in patients heterozy-0015-0282/09/$36.00Copyright ª2009 Americangous for the Q188R mutation or the Duarte variant. Con-versely, no increased risk for premature ovarian failure,infertility, or spontaneous pregnancy loss was noted inwomen with a galactosemic child (4). Moreover, Mlinaret al. purported that the 50% decrease in GALT activity inQ188R or K285 N heterozygotes or the 25% decrease inGALT activity in Duarte heterozygotes does not compromiseovarian function (5). In our case, a notable spectrum beganwith poor obstetric outcome, continued with infertility andinadequate ovarian response to stimulation, and manifestedas TFF or poor-quality embryos despite a galactose-freediet, all of which might have been related to impaired ovarianfunction. Even though the genetic composition of the malepartner may have contributed to the spectrum of poor repro-ductive outcome in our case, and despite no clear connectiondemonstrated, it cannot simply be ruled out that there is notany association between premature ovarian failure or dimin-ished ovarian reserve and mutations in GALT gene.Murat Sonmezer, M.D.Batuhan €Ozmen, M.D.Cem Somer Atabekoglu, M.D.Ankara University, Department of Obstetrics andGynecology, IVF Unit, Ankara, TurkeyVolkan Baltaci, M.D.Ufuk University, Department of Human Genetics, Ankara,TurkeyJune 7, 2009REFERENCES1. Gubbels CS, Kuppens SM, Bakker JA, Konings CJ, Wodzig KW, de Sain-van der Velden MG, et al. Pregnancy in classic galactosemia despite un-detectable antim€ullerian hormone. Fertil Steril 2009;91:1293.2. Elsas LJ, Dembure PP, Langley S, Paulk EM, Hjelm LN, Fridovich-Keil J.A common mutation associated with the Duarte galactosemia allele. Am JHum Genet 1994;54:1030–6.3. Cramer DW, Barbieri RL, Xu H, Reichardt JK. Determinants of basal fol-licle-stimulating hormone levels in premenopausal women. J Clin Endo-crinol Metab 1994;79:1105–9.4. Sayle AE, Cooper GS, Savitz DA. Menstrual and reproductive history ofmothers of galactosemic children. Fertil Steril 1996;65:534–8.5. Mlinar B, Gersak K, Karas N, Zitnik IP, Battelino T, Lukac-Bajalo J.Galactose-1-phosphate uridyl transferase gene mutations in women withpremature ovarian failure. Fertil Steril 2005;84:253–5.doi:10.1016/j.fertnstert.2009.06.051Fertility and Sterility Vol. 92, No. 4, October 2009 e43Society for Reproductive Medicine, Published by Elsevier Inc.

Do patients with heterozygote mutations in GALT gene have increased risk for impaired reproductive functions?

http://acikerisim.ufuk.edu.tr/xmlui/bitstream/20.500.14065/1781/1/10-%20Do%20patients%20with%20heterozygote%20mutations%20in%20GALT%20gene%20have%20increased%20risk%20for%20impaired%20reproductive%20functions.pdf

Do patients with heterozygote mutations in GALT gene have increased risk for impaired reproductive functions?

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