Britt van Erven1, Gerard T Berry2, David Cassiman3, Geraldine Connolly4, Maria Forga5, Matthias Gautschi6, Cynthia S Gubbels7, Carla E M Hollak8, Mirian C Janssen9, Ina Knerr10, Philippe Labrune11, Janneke G Langendonk12, Katrin Õunap13, Abel Thijs14, Rein Vos15, Saskia B Wortmann16, M Estela Rubio-Gozalbo17. 1. Department of Pediatrics and Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, the Netherlands. 2. Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts. 3. Department of Gastroenterology-Hepatology, Metabolic Center, University Hospitals Leuven, Leuven, Belgium. 4. Rotunda Hospital and Temple Street Children's University Hospital, Dublin, Ireland. 5. Endocrinology and Nutrition Department, Hospital Clinic, Barcelona, Spain. 6. University Children's Hospital, Pediatric Endocrinology, Diabetes, and Metabolism, and Institute of Clinical Chemistry, Inselspital, University of Bern, Bern, Switzerland. 7. Division of Genetics and Genomics, Boston Children's Hospital/Harvard Medical School/Broad Institute of Massachusetts Institute of Technology and Harvard, Boston, Massachusetts. 8. Division of Endocrinology and Metabolism, Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands. 9. Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands. 10. National Centre for Inherited Metabolic Disorders, Temple Street Children's University Hospital, Dublin, Ireland. 11. Hôpital Antoine Béclère, Centre de Référence Maladies Héréditaires du Métabolisme Hépatique, Hôpitaux Universitaires Paris Sud, Clamart, France. 12. Center for Lysosomal and Metabolic Diseases, Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands. 13. Department of Clinical Genetics, United Laboratories, Tartu University Hospital, and Department of Pediatrics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia. 14. Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands. 15. Department of Methodology and Statistics, School for Public Health and Primary Care, Maastricht University, Maastricht, the Netherlands. 16. Children's Hospital, Salzburger Landeskliniken and Paracelsus Medical University, Salzburg, Austria. 17. Department of Pediatrics and Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, the Netherlands. Electronic address: estela.rubio@mumc.nl.
Abstract
OBJECTIVE: To study pregnancy chance in adult women with classic galactosemia and primary ovarian insufficiency. Despite dietary treatment, >90% of women with classic galactosemia develop primary ovarian insufficiency, resulting in impaired fertility. For many years, chance of spontaneous conception has not been considered, leading to counseling for infertility. But an increasing number of reports on pregnancies in this group questions whether current counseling approaches are correct. DESIGN: Multicenter retrospective observational study. SETTING: Metabolic centers. PATIENT(S): Adult women (aged >18 y) with confirmed classic galactosemia and primary ovarian insufficiency were included. INTERVENTION(S): Participants and medical records were consulted to obtain study data in a standardized manner with the use of a questionnaire. MAIN OUTCOME MEASURE(S): Conception opportunities, time to pregnancy, pregnancy outcome, hormone replacement therapy use, fertility counseling, and the participants' vision of fertility were evaluated. Potential predictive factors for increased pregnancy chance were explored. RESULT(S): Eighty-five women with classic galactosemia and primary ovarian insufficiency participated. Twenty-one women actively attempted to conceive or did not take adequate contraceptive precautions. Of these 21 women, nine became pregnant spontaneously (42.9%). This was higher than reported in primary ovarian insufficiency due to other causes (5%-10%). After a period of 12 months, a cumulative proportion of 27.8% of couples had conceived, which increased to 48.4% after 24 months and 61.3% after 27 months. Predictive factors could not be identified. A considerable miscarriage rate of 30% was observed (6 of 20 pregnancies). Although a substantial proportion of women expressed a child-wish (n = 28/53; 52.8%), the vast majority of participants (n = 43/57; 75.4%) considered conceiving to be highly unlikely, owing to negative counseling in the past. CONCLUSION(S): The pregnancy rate in women with classic galactosemia and primary ovarian insufficiency was higher than for women with primary ovarian insufficiency of any cause. This shifting paradigm carries significant implications for fertility counseling and potential application of fertility preservation techniques.
OBJECTIVE: To study pregnancy chance in adult women with classic galactosemia and primary ovarian insufficiency. Despite dietary treatment, >90% of women with classic galactosemia develop primary ovarian insufficiency, resulting in impaired fertility. For many years, chance of spontaneous conception has not been considered, leading to counseling for infertility. But an increasing number of reports on pregnancies in this group questions whether current counseling approaches are correct. DESIGN: Multicenter retrospective observational study. SETTING: Metabolic centers. PATIENT(S): Adult women (aged >18 y) with confirmed classic galactosemia and primary ovarian insufficiency were included. INTERVENTION(S): Participants and medical records were consulted to obtain study data in a standardized manner with the use of a questionnaire. MAIN OUTCOME MEASURE(S): Conception opportunities, time to pregnancy, pregnancy outcome, hormone replacement therapy use, fertility counseling, and the participants' vision of fertility were evaluated. Potential predictive factors for increased pregnancy chance were explored. RESULT(S): Eighty-five women with classic galactosemia and primary ovarian insufficiency participated. Twenty-one women actively attempted to conceive or did not take adequate contraceptive precautions. Of these 21 women, nine became pregnant spontaneously (42.9%). This was higher than reported in primary ovarian insufficiency due to other causes (5%-10%). After a period of 12 months, a cumulative proportion of 27.8% of couples had conceived, which increased to 48.4% after 24 months and 61.3% after 27 months. Predictive factors could not be identified. A considerable miscarriage rate of 30% was observed (6 of 20 pregnancies). Although a substantial proportion of women expressed a child-wish (n = 28/53; 52.8%), the vast majority of participants (n = 43/57; 75.4%) considered conceiving to be highly unlikely, owing to negative counseling in the past. CONCLUSION(S): The pregnancy rate in women with classic galactosemia and primary ovarian insufficiency was higher than for women with primary ovarian insufficiency of any cause. This shifting paradigm carries significant implications for fertility counseling and potential application of fertility preservation techniques.
Authors: M Haskovic; W J Poot; R J T van Golde; S H Benneheij; E Oussoren; G M W R de Wert; A Krumeich; M Estela Rubio-Gozalbo Journal: J Inherit Metab Dis Date: 2018-04-18 Impact factor: 4.982
Authors: M E Rubio-Gozalbo; M Haskovic; A M Bosch; B Burnyte; A I Coelho; D Cassiman; M L Couce; C Dawson; D Demirbas; T Derks; F Eyskens; M T Forga; S Grunewald; J Häberle; M Hochuli; A Hubert; H H Huidekoper; P Janeiro; J Kotzka; I Knerr; P Labrune; Y E Landau; J G Langendonk; D Möslinger; D Müller-Wieland; E Murphy; K Õunap; D Ramadza; I A Rivera; S Scholl-Buergi; K M Stepien; A Thijs; C Tran; R Vara; G Visser; R Vos; M de Vries; S E Waisbren; M M Welsink-Karssies; S B Wortmann; M Gautschi; E P Treacy; G T Berry Journal: Orphanet J Rare Dis Date: 2019-04-27 Impact factor: 4.123
Authors: Magd A Kotb; Lobna Mansour; Christine William Shaker Basanti; Wael El Garf; Ghada I Z Ali; Sally T Mostafa El Sorogy; Inas E M Kamel; Naglaa M Kamal Journal: J Adv Res Date: 2018-02-23 Impact factor: 10.479