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The Role of Folliculo-Luteal Insufficiency in the Emergence of Random Chromosomal Abnormalities

  • György Siklósi
Chapter
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Abstract

It is a proven fact that about 50 % of pregnancy losses are caused by randomly occurring, mainly numerical chromosomal abnormalities (CA) that emerge during oogenesis (sometimes during spermiogenesis). Based on this, the normalisation of folliculo-luteal function (FLF) and placentation – if this did not influence the emergence of CAs – would be able to decrease the prevalence of miscarriage by half at most, while the actual miscarriage rate is only a fraction of this number.

In recurrent miscarriage, the normalisation of FLF decreased the occurrence of miscarriage by an order of magnitude compared to the untreated control group (39.4 and 4.5 %). Even if CAs were the cause of every abortion with physiological FLF, the incidence of CAs decreased to one-quarter of the expected 19.7 % (50 %). In case of unexplained infertility (UI), the prevalence of miscarriage was 41.2 % in untreated patients and 3.2 % with physiological FLF, which is less than one-sixth of the expected 20.6 %.

This decline is even more dramatic in patients over 35 years of age, where CAs are the most common cause of abortion. In recurrent miscarriage patients with an age of ≥35 years, the miscarriage rate was 54.5 % in the untreated group and 4.7 % with physiological FLF. Miscarriage rates in the untreated and physiological group of ≥35 years with UI were 65.2 and 6.9 % (Chaps. 5 and 6).

In patients with habitual abortion, the occurrence of miscarriage was 97 % (70/72) with confirmed FLF insufficiency and 4.5 % (28/627) with physiological FLF. Our results regarding UI were similar: pregnancy loss occurred in 96 % (47/49) with insufficient FLF and in 3.2 % (27/835) with physiological FLF.

These findings can only be interpreted if we assume that the normalisation of folliculogenesis dramatically decreases the emergence of random, mainly numerical CAs.

Keywords

Granulosa Cell Pregnancy Loss Meiotic Division Mitotic Division Miscarriage Rate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Al-Inany H, Azab H, El-Khayat W, Nada A, El-Khattan E, Abou-Setta AM. The effectiveness of clomiphene citrate in LH surge suppression in women undergoing IUI: a randomized controlled trial. Fertil Steril. 2010;94(6):2167–71.CrossRefPubMedGoogle Scholar
  2. Ayabe T, Tetsu T, Tsutsami O, Mitsuhashi N, Momoeda M, Taketani Y. Impaired follicular growth and abnormal luteinizing hormone surge in luteal phase defect. Fertil Steril. 1994;81:652–6.CrossRefGoogle Scholar
  3. Beall S, Brenner C, Segars J. Oocyte maturation failure: a syndrome of bad eggs. Fertil Steril. 2010;94:2507–13.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Branch DW, Gibson M, Silver RM. Recurrent miscarriage. N Engl J Med. 2010;363:1740–7.CrossRefPubMedGoogle Scholar
  5. Channing CP, Hillensjo T, Schaerf FW. Hormonal control of oocyte meiosis, ovulation and luteinization in mammals. Clin Endocrinol Metab. 1978;7(3):601–24.CrossRefPubMedGoogle Scholar
  6. Desjardins MK, Stephenson MD. “Information-rich” reproductive outcomes in carriers of a structural chromosome rearrangement ascertained on the basis of recurrent pregnancy loss. Fertil Steril. 2012;97(4):894–903.CrossRefPubMedGoogle Scholar
  7. Handyside AH. Molecular origin of female meiotic aneuploidies. Biochim Biophys Acta. 2012;1822:1913–20.CrossRefPubMedGoogle Scholar
  8. Heikinheimo O, Gibbons WE. The molecular mechanisms of oocyte maturation and early embryonic development are unveiling new insights into reproductive medicine. Mol Hum Reprod. 1998;4:745–56.CrossRefPubMedGoogle Scholar
  9. Kochhar PK, Ghosh P. Reproductive outcome of couples with recurrent miscarriage and balanced chromosomal abnormalities. J Obstet Gynaecol Res. 2013;39(1):113–20.CrossRefPubMedGoogle Scholar
  10. Mantikou E, Wong KM, Repping S, Mastenbroek S. Molecular origin of mitotic aneuploidies in preimplantation embryos. Biochim Biophys Acta. 2012;1822(12):1921–30.CrossRefPubMedGoogle Scholar
  11. Marquard K, Westphal LM, Milki AA, Lathi RB. Etiology of recurrent pregnancy loss in women over the age of 35 years. Fertil Steril. 2010;94:1473–7.CrossRefPubMedGoogle Scholar
  12. Mihm M, Gangooly S, Muttukrishna S. The normal menstrual cycle in women. Anim Reprod Sci. 2011;124(3–4):229–36.CrossRefPubMedGoogle Scholar
  13. Pohler KG, Geary TW, Atkins JA, Perry GA, Jinks EM, Smith MF. Follicular determinants of pregnancy establishment and maintenance. Cell Tissue Res. 2012;349:649–64.CrossRefPubMedGoogle Scholar
  14. Rai R, Regan L. Recurrent miscarriage. Lancet. 2006;368:601–11.CrossRefPubMedGoogle Scholar
  15. Sánchez F, Smitz J. Molecular control of oogenesis. Biochim Biophys Acta. 2012;1822:1896–912.CrossRefPubMedGoogle Scholar
  16. Tang AW, Quenby S. Recent thoughts on management and prevention of recurrent early pregnancy loss. Curr Opin Obstet Gynecol. 2010;22:446–51.CrossRefPubMedGoogle Scholar
  17. Tempest HG, Ko E, Rademaker A, Chan P, Robaire B, Martin RH. Intra-individual and inter-individual variations in sperm aneuploidy frequencies in normal men. Fertil Steril. 2009;91(1):185–92.CrossRefPubMedGoogle Scholar
  18. Tempest HG. Meiotic recombination errors, the origin of sperm aneuploidy and clinical recommendations. Syst Biol Reprod Med. 2011;57(1–2):93–101.CrossRefPubMedGoogle Scholar
  19. Templado C, Uroz L, Estop A. New insights on the origin and relevance of aneuploidy in human spermatozoa. Mol Hum Reprod. 2013;19(10):634–43.CrossRefPubMedGoogle Scholar
  20. Templado C, Vidal F, Estop A. Aneuploidy in human spermatozoa. Cytogenet Genome Res. 2011;133(2–4):91–9.CrossRefPubMedGoogle Scholar
  21. van den Berg MM, van Maarle MC, van Wely M, Goddijn M. Genetics of early miscarriage. Biochim Biophys Acta. 2012;1822:1951–9.CrossRefPubMedGoogle Scholar
  22. Zhao P, Qiao J, Huang S, et al. Gonadotropin-induced paracrine regulation of human oocyte maturation by BDNF and GDNF secreted by granulosa cells. Hum Reprod. 2011;26:695–702.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • György Siklósi
    • 1
  1. 1.Semmelweis University Second Department of Obstetrics and GynecologyBudapestHungary

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