CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2017; 77(12): 1312-1319
DOI: 10.1055/s-0043-122279
GebFra Science
Original Article/Originalarbeit
Georg Thieme Verlag KG Stuttgart · New York

Preconception Optimization of Glucose and Insulin Metabolism in Women Wanting to Conceive – High Rate of Spontaneous Conception Prior to Planned Assisted Reproduction

Artikel in mehreren Sprachen: English | deutsch
Sara Fill Malfertheiner
1   Profertilita – Fachklinik für Fruchtbarkeitsmedizin, Regensburg, Germany
2   Klinik für Geburtshilfe und Frauenheilkunde der Universität Regensburg – Krankenhaus Barmherzige Brüder – Klinik St. Hedwig, Regensburg, Germany
,
Dagmar Gutknecht
1   Profertilita – Fachklinik für Fruchtbarkeitsmedizin, Regensburg, Germany
,
Monika Bals-Pratsch
1   Profertilita – Fachklinik für Fruchtbarkeitsmedizin, Regensburg, Germany
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Publikationsverlauf

received 23. Juni 2017
revised 02. November 2017

accepted 03. November 2017

Publikationsdatum:
18. Dezember 2017 (online)

Abstract

Background A hyperglycemic metabolic status with insulin resistance can have a negative effect on fertility and pregnancy outcomes. The aim of this retrospective study was to investigate disorders of glucose and insulin metabolism in women wanting to conceive who conceived spontaneously prior to planned assisted reproduction (ART). Associated risk factors of patients in terms of live births and miscarriages were also analyzed.

Method Out of total study population of 589 pregnancies, the pregnancies of 129 women wishing to have children who conceived spontaneously prior to planned ART were analyzed in more detail. A 75 g OGTT (OGTT: oral glucose tolerance test) was carried out prior to conception and after determination of pregnancy, including glucose measurement and testing of insulin resistance. If anomalies or risk factors for gestational diabetes (GDM) were detected, patients received metformin therapy prior to conception (off-label use). The course and outcome of pregnancies in the defined cohort were recorded.

Results The rate of spontaneous conception before planned ART after treatment for disorders of glucose/insulin metabolism was 21.9% (n = 129/589). 66.7% of the 129 pregnancies resulted in a live birth, 32 patients had a miscarriage. 76.0% of patients were treated with metformin (off-label use) for polycystic ovary syndrome (PCOS), positive risk profile for GDM, or abnormal glucose/insulin metabolism prior to conception. 55.8% of the cohort developed GDM. The insulin requirements of patients with GDM differed significantly depending on their metformin intake. 24.6% of GDM patients receiving metformin treatment developed GDM requiring insulin treatment compared to 53.8% who did not receive metformin medication. The PCOS rate in the study population who had live births was significantly higher (57.0%) than in the group who had miscarriages (31.3%). There were no significant differences with regard to rate of live births and rate of miscarriages with/without metformin treatment and GDM and metformin intake.

Conclusion The high rate of spontaneous conceptions in the cohort of women wishing to conceive emphasizes the importance of optimizing glucose/insulin metabolism prior to conception. The high rate of GDM in a cohort of pregnant women with a history of sterility also emphasizes the importance of expanding diagnostic testing for sterility to include the investigation of glucose metabolism and testing for insulin resistance. It is possible that PCOS patients in particular could benefit from treatment with metformin prior to conception, and this could explain the high rate of live births in this patient cohort.

 
  • References/Literatur

  • 1 Ombelet W, Cooke I, Dyer S. et al. Infertility and the provision of infertility medical services in developing countries. Hum Reprod Update 2008; 14: 605-621 doi:10.1093/humupd/dmn042
  • 2 Williams T, Mortada R, Porter S. Diagnosis and treatment of polycystic ovary syndrome. Am Fam Physician 2016; 94: 106-113
  • 3 Hart RJ. Physiological aspects of female fertility: role of the environment, modern lifestyle, and genetics. Physiol Rev 2016; 96: 873-909 doi:10.1152/physrev.00023.2015
  • 4 Pasquali R, Patton L, Gambineri A. Obesity and infertility. Curr Opin Endocrinol Diabetes Obes 2007; 14: 482-487 doi:10.1097/MED.0b013e3282f1d6cb
  • 5 Mensink G, Schienkiewitz A, Haftenberger M. et al. Übergewicht und Adipositas in Deutschland. Bundesgesundheitsbl 2013; 56: 786-794 doi:10.1007/s00103-012-1656-3
  • 6 Balasch J, Gratacós E. Delayed childbearing. Curr Opin Obstet Gynecol 2012; 24: 187-193 doi:10.1097/GCO.0b013e3283517908
  • 7 S3-Leitlinie Gestationsdiabetes mellitus (GDM), Diagnostik, Therapie und Nachsorge 2017. Überarbeitungsversion. Online: https://www.deutsche-diabetes-gesellschaft.de/fileadmin/Redakteur/Leitlinien/Leitlinien-zur-Konsultation/GDM-Leitlinie-_gesamttext.pdf last access: 12.09.2017
  • 8 Weiss U, Cervar M, Puerstner P. et al. Hyperglycaemia in vitro alters the proliferation and mitochondrial activity of the choriocarcinoma cell lines BeWo, JAR and JEG-3 as models for human first-trimester trophoblast. Diabetologia 2001; 44: 209-219 doi:10.1007/s001250051601
  • 9 Melchior H, Kurch-Bek D, Mund M. The prevalence of gestational diabetes: a population-based analysis of a nationwide screening program. Dtsch Arztebl Int 2017; 114: 412-418 doi:10.3238/arztebl.2017.0412
  • 10 Zeiher J, Varnaccia G, Jordan S. et al. Was sind die Einflussfaktoren kindlicher Adipositas?. Bundesgesundheitsbl 2016; 59: 1465-1475 doi:10.1007/s00103-016-2441-5
  • 11 Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care 2004; 27: 1487-1495 doi:10.2337/diacare.27.6.1487
  • 12 Rowan JA, Hague WM, Gao W. et al. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med 2008; 358: 2003-2015 doi:10.1056/NEJMoa0707193
  • 13 Poolsup N, Suksomboon N, Amin M. et al. Efficacy and safety of oral antidiabetic drugs in comparison to insulin in treating gestational diabetes mellitus: a meta-analysis. PLoS One 2014; 9: e109985 doi:10.1371/journal.pone.0109985
  • 14 Butalia S, Gutierrez L, Lodha A. et al. Short- and long-term outcomes of metformin compared with insulin alone in pregnancy: a systematic review and meta-analysis. Diabet Med 2017; 34: 27-36 doi:10.1111/dme.13150
  • 15 Niromanesh S, Alavi A, Sharbaf FR. et al. Metformin compared with insulin in the management of gestational diabetes mellitus: A randomized clinical trial. Diabetes Res Clin Pract 2012; 98: 422-429 doi:10.1016/j.diabres.2012.09.031
  • 16 Spaulonci CP, Bernardes LS, Trindade TC. et al. Randomized trial of metformin vs. insulin in the management of gestational diabetes. Am J Obstet Gynecol 2013; 209: 34.e1-34.e7 doi:10.1016/j.ajog.2013.03.022
  • 17 McGrath RT, Glastras SJ, Hocking S. et al. Use of metformin earlier in pregnancy predicts supplemental insulin therapy in women with gestational diabetes. Diabetes Res Clin Pract 2016; 116: 96-99 doi:10.1016/j.diabres.2016.04.051
  • 18 Tan X, Li S, Chang Y. et al. Effect of metformin treatment during pregnancy on women with PCOS: a systematic review and meta-analysis. Clin Invest Med 2016; 39: E120-E131
  • 19 Kentenich H, Jank A. Fortpflanzung im höheren Alter. Gynäkologische Endokrinologie 2016; 14: 105-110 doi:10.1007/s10304-016-0062-6
  • 20 AQUA-Institut. Bundesauswertung zum Erfassungsjahr 2014; 16/1 – Geburtshilfe; Qualitätsindikatoren. 2015 Online: http://www.sqg.de/downloads/Bundesauswertungen/2014/bu_Gesamt_16N1-GEBH_2014.pdf last access: 09.08.2016
  • 21 Hammarberg K, Clarke VE. Reasons for delaying childbearing–a survey of women aged over 35 years seeking assisted reproductive technology. Aust Fam Physician 2005; 34: 187-188 206
  • 22 Sendag F, Terek MC, Itil IM. et al. Maternal and perinatal outcomes in women with gestational diabetes mellitus as compared to nondiabetic controls. J Reprod Med 2001; 46: 1057-1062
  • 23 Michael Weindling A. Offspring of diabetic pregnancy: short-term outcomes. Semin Fetal Neonatal Med 2009; 14: 111-118 doi:10.1016/j.siny.2008.11.007
  • 24 Yogev Y, Langer O. Spontaneous preterm delivery and gestational diabetes: the impact of glycemic control. Arch Gynecol Obstet 2007; 276: 361-365 doi:10.1007/s00404-007-0359-8
  • 25 Dörr HG, Dötsch J. „Small for gestational age“ (SGA) – Risiko für ovarielle Hyperandrogenämie und PCO? Gynäkologische Endokrinologie. 2005; 176-180 doi:10.1007/s10304-005-0119-4
  • 26 Ibáñez L, Potau N, Ferrer A. et al. Anovulation in eumenorrheic, nonobese adolescent girls born small for gestational age: Insulin sensitization induces ovulation, increases lean body mass, and reduces abdominal fat excess, dyslipidemia, and subclinical hyperandrogenism. J Clin Endocrinol Metab 2002; 87: 5702-5705 doi:10.1210/jc.2002-020926
  • 27 Dempsey JC, Sorensen TK, Williams MA. et al. Prospective study of gestational diabetes mellitus risk in relation to maternal recreational physical activity before and during pregnancy. Am J Epidemiol 2004; 159: 663-670
  • 28 Metzger BE, Lowe LP, Dyer AR. et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008; 358: 1991-2002 doi:10.1056/NEJMoa0707943
  • 29 Schmitz S, Groten T, Schleussner E. et al. Gestational diabetes mellitus: an evaluation of gynecologistsʼ knowledge of guidelines and counseling behavior. Arch Gynecol Obstet 2016; 294: 1209-1217 doi:10.1007/s00404-016-4161-3
  • 30 Damm P, Houshmand-Oeregaard A, Kelstrup L. et al. Gestational diabetes mellitus and long-term consequences for mother and offspring: a view from Denmark. Diabetologia 2016; 59: 1396-1399 doi:10.1007/s00125-016-3985-5
  • 31 Hakanen T, Saha MT, Salo MK. et al. Mothers with gestational diabetes are more likely to give birth to children who experience early weight problems. Acta Paediatr 2016; 105: 1166-1172 doi:10.1111/apa.13468