In Vitro Fertilization(IVF) for Gilbert Syndrome Associated with ßeta-Thalassemia, A Case Report

  • Dragos Albu UMF Carol Davila, Dionisie Lupu street no 37, Bucharest 20021, Romania
  • Alice Albu UMF Carol Davila, Dionisie Lupu street no 37, Bucharest 20021, Romania
  • Roxana Bohiltea UMF Carol Davila, Dionisie Lupu street no 37, Bucharest 20021, Romania
Keywords: in vitro fertilization, syndrome Gilbert, ß thalassemia, aromatase inhibitors

Abstract

The Gilbert syndrome is a familial tip of a benign condition characterized by a high level of unconjugated bilirubin without hemolysis or liver disease. In this syndrome, there is a mutation of the UGT1A1 gene on the long arm (q) of chromosome 2, which synthesize the enzyme uridine diphosphate-glucuronosyltransferase-1A1 (UGT1A1), that conjugate bilirubin. Hepatic glucuronidation activity is diminished by 30%. The association between Gilbert syndrome and in vitro fertilization (IVF) is not yet presented in the literature. A 34-year-old nulliparous woman presented to our clinic for primary infertility. Antimullerian hormone level was normal: 3.5 ng/ml. Her partner sperm analysis showed severe oligoasthenoteratozoospermia: 5milion/ml concentration, 25 % progressive motility, 3% standard form. She was known for Gilbert syndrome and ßeta thalassemia. She decided to go for in vitro fertilization (IVF) with ICSI (intracytoplasmic sperm injection). We used a short antagonist protocol with letrozole 2.5mg twice a day and 150 UI menotropins to avoid estradiol rising, which could determine, in her case, the level of serum bilirubin to increase. We collected fourteen oocytes; twelve of them were in metaphase II, nine fertilized by ICSI, and we obtained three good blastocyst 4aa, 4ab, and 4ba (according to Gardner-Schoolcraft criteria). We transferred one blastocyst, and ß HCG was negative on day eleven after embryo transfer. Next month, we transferred on a natural cycle one blastocyst: 4ab after thawing. Ultrasound confirmed a single pregnancy with a heartbeat. In this Gilbert syndrome, to avoid estradiol rising, we used aromatase inhibitors in conjunction with gonadotropins for IVF ovarian stimulation.

References

Karl-Heinz Wagner, Ryan G. Shiels, Claudia Anna Lang, Nazlisadat Seyed Khoei & Andrew C. Bulmer . Diagnostic criteria and contributors to Gilbert’s syndrome, Critical Reviews in Clinical Laboratory Sciences, 55:2,129-139, DOI: 10.1080/10408363.2018.1428526

Mohan M, P LS, Reddy PV. Pregnancy with gilbert syndrome - a case report. J Clin Diagn Res. 2014 Jun;8(6):OD01-2. doi: 10.7860/JCDR/2014/9327.4426. Epub 2014 Jun 20. PMID: 25121033; PMCID: PMC4129268.

Piter J. Bosma, The Genetic Basis of the Reduced Expression of Bilirubin UDP-Glucuronosyltransferase1 in Gilbert's Syndrome N Engl J Med 1995; 333:1171-1175

DOI: 10.1056/NEJM199511023331802

Paull Radu, Jacob Atsmon, Gilbert’s syndrome-clinical and pharmacological implication. IMAJ 2001; 3; August; 593-598

Fretzayas, A., Moustaki, M., Liapi, O. et al. Gilbert syndrome. Eur J Pediatr (2012) 171: 11. https://doi.org/10.1007/s00431-011-1641-0

Galanello, R. , Perseu, L. , Melis, M. A., Cipollina, L. , Barella, S. , Giagu, N. , Turco, M. P., Maccioni, O. and Cao, A. (1997), Hyperbilirubinaemia in heterozygous β‐thalassaemia is related to co‐inherited Gilbert's syndrome. British Journal of Haematology, 99: 433-436. doi:10.1046/j.1365-2141.1997.3703182

Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011 Jun;26(6):1270-83. doi: 10.1093/humrep/der037. Epub 2011 Apr 18. PMID: 21502182.

G M Hirschfield, Gilbert’s syndrome: an overview for clinical biochemists. (2006). Annals of Clinical Biochemistry, 43(5), 340-343

Thoguluva Chandrasekar V, John S. Gilbert Syndrome. [Updated 2021 Sep 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470200/

Kamal S, Abdelhakam S, Ghoraba D, Massoud Y, Aziz KA, Hassan H, Hafez T, Abdel Sallam A. The frequency, clinical course, and health related quality of life in adults with Gilbert's syndrome: a longitudinal study. BMC Gastroenterol. 2019 Feb 4;19(1):22. doi: 10.1186/s12876-019-0931-2. PMID: 30717703; PMCID: PMC6360704.

Saki F, Hemmati F, Haghighat M. Prevalence of Gilbert syndrome in parents of neonates with pathologic indirect hyperbilirubinemia. Ann Saudi Med. 2011 Mar-Apr;31(2):140-4. doi: 10.4103/0256-4947.77498. PMID: 21403409; PMCID: PMC3102472.

Published
2021-10-30
Section
Articles