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Lutealphaseninsuffizienz bei Kinderwunsch

Diagnostik und Therapieansätze

Luteal phase insufficiency and desire to become pregnant

Diagnostics and treatment approaches

  • Leitthema
  • Published:
Gynäkologische Endokrinologie Aims and scope

Zusammenfassung

Die zweite Zyklushälfte ist charakterisiert durch die Sekretionsleistung des Corpus luteum nach erfolgter Freisetzung der Eizelle bei der Ovulation. Nach Aufbau des Endometriums unter dem Einfluss steigender Östrogenspiegel in der ersten Zyklushälfte bewirkt Progesteron als Schlüsselhormon der zweiten Zyklushälfte die Transformation des Endometriums und ermöglicht so Eintritt und Erhalt einer Schwangerschaft. Eine unzureichende Sekretionsleistung des Corpus luteum oder die unzureichende Transformationswirkung am Endometrium führt zur Lutealphaseninsuffizienz. Klinisch wird darunter ein auffälliges Zyklusmuster mit verkürzter zweiter Zyklushälfte oder verlängerten prämenstruellen (Zwischen‑)Blutungen verstanden. Ergänzende diagnostische Tests in der zweiten Zyklushälfte wie die Progesteronbestimmung im Serum oder eine Endometriumbiopsie sind in der Aussagekraft eingeschränkt. Ursächlich geht der Lutealphaseninsuffizienz typischerweise eine Reifungsstörung des Follikels voraus, die insbesondere bei Kinderwunsch der Patientin auch zuallererst diagnostiziert und therapiert werden sollte. Bei speziellen Fragestellungen wie einer habituellen Abortneigung wird der Nutzen einer zusätzlichen Progesteronsubstitution diskutiert, nach vorausgehender ovarieller Stimulationstherapie im Rahmen assistierter Reproduktionsverfahren ist dieser unstrittig belegt. Eine symptomorientierte Therapie mit Progesteron oder synthetischen Gestagenen in der zweiten Zyklushälfte sollte ansonsten der alleinigen Zyklusregulierung außerhalb des Kinderwunschs vorbehalten sein.

Abstract

The second half of the cycle is characterized by the secretory capacity of the corpus luteum following successful release of the ovum during ovulation. After endometrial proliferation under the influence of rising estrogen levels in the first half of the cycle, progesterone as the key hormone in the second half of the cycle causes endometrial transformation and receptivity for the initiation und maintenance of pregnancy. Luteal phase insufficiency is determined by insufficient secretion by the corpus luteum or insufficient transformation of the endometrium. This appears clinically as an abnormal cycle pattern with a shortened second half of the cycle, prolonged premenstrual bleeding or spotting. A benefit from additional diagnostic tests in the second half of the cycle, such as progesterone measurement in the serum or endometrial biopsy, is doubtful. As luteal phase insufficiency is causally related to a preceding disturbed follicular maturation, this should be diagnosed and primarily treated in subfertility of patients wishing to become pregnant. In patients with recurrent miscarriages adding progesterone or other progestogens may be useful, whereas its value following ovarian stimulation during assisted reproductive procedures is undisputed. Symptom-oriented therapy using progestogens or synthetic gestagens in the second half of the cycle should otherwise be reserved for the purpose of regulating the cycle outside the desire to become pregnant.

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Literatur

  1. Altmae S, Martinez-Conejero JA, Salumets A et al (2010) Endometrial gene expression analysis at the time of embryo implantation in women with unexplained infertility. Mol Hum Reprod 16:178–187

    Article  CAS  PubMed  Google Scholar 

  2. Branch DW, Gibson M, Silver RM (2010) Clinical practice. Recurrent miscarriage. N Engl J Med 363:1740–1747

    Article  CAS  PubMed  Google Scholar 

  3. Brown JB (2011) Types of ovarian activity in women and their significance: the continuum (a reinterpretation of early findings). Hum Reprod Update 17:141–158

    Article  CAS  PubMed  Google Scholar 

  4. Chinta P, Rebekah G, Kunjummen AT et al (2020) Revisiting the role of serum progesterone as a test of ovulation in eumenorrheic subfertile women: a prospective diagnostic accuracy study. Fertil Steril 114(6):1315–1321. https://doi.org/10.1016/j.fertnstert.2020.06.030

    Article  CAS  PubMed  Google Scholar 

  5. Coomarasamy A, Williams H, Truchanowicz E et al (2015) A randomized trial of progesterone in women with recurrent miscarriages. N Engl J Med 373:2141–2148

    Article  CAS  PubMed  Google Scholar 

  6. Coutifaris C, Myers ER, Guzick DS et al (2004) Histological dating of timed endometrial biopsy tissue is not related to fertility status. Fertil Steril 82:1264–1272

    Article  PubMed  Google Scholar 

  7. Crosignani PG, Rubin BL (2000) Optimal use of infertility diagnostic tests and treatments. The ESHRE Capri workshop group. Hum Reprod 15:723–732

    Article  CAS  PubMed  Google Scholar 

  8. Csapo AI, Pulkkinen MO, Ruttner B et al (1972) The significance of the human corpus luteum in pregnancy maintenance. I. Preliminary studies. Am J Obstet Gynecol 112:1061–1067

    Article  CAS  PubMed  Google Scholar 

  9. Davis OK, Berkeley AS, Naus GJ et al (1989) The incidence of luteal phase defect in normal, fertile women, determined by serial endometrial biopsies. Fertil Steril 51:582–586

    Article  CAS  PubMed  Google Scholar 

  10. De Souza MJ, Toombs RJ, Scheid JL et al (2010) High prevalence of subtle and severe menstrual disturbances in exercising women: confirmation using daily hormone measures. Hum Reprod 25:491–503

    Article  CAS  PubMed  Google Scholar 

  11. Devilbiss EA, Stanford JB, Mumford SL et al (2020) Sporadic anovulation is not an important determinant of becoming pregnant and time to pregnancy among eumenorrheic women: a simulation study. Paediatr Perinat Epidemiol. https://doi.org/10.1111/ppe.12692

    Article  PubMed  Google Scholar 

  12. Devoto L, Kohen P, Munoz A et al (2009) Human corpus luteum physiology and the luteal-phase dysfunction associated with ovarian stimulation. Reprod Biomed Online 18(2):19–24

    Article  PubMed  Google Scholar 

  13. Diaz-Gimeno P, Horcajadas JA, Martinez-Conejero JA et al (2011) A genomic diagnostic tool for human endometrial receptivity based on the transcriptomic signature. Fertil Steril 95:50–60

    Article  CAS  PubMed  Google Scholar 

  14. Ellinwood WE, Norman RL, Spies HG (1984) Changing frequency of pulsatile luteinizing hormone and progesterone secretion during the luteal phase of the menstrual cycle of rhesus monkeys. Biol Reprod 31:714–722

    Article  CAS  PubMed  Google Scholar 

  15. Haas DM, Ramsey PS (2013) Progestogen for preventing miscarriage. Cochrane Database Syst Rev 10:CD3511

    Google Scholar 

  16. Jarvela IY, Ruokonen A, Tekay A (2008) Effect of rising hCG levels on the human corpus luteum during early pregnancy. Hum Reprod 23:2775–2781

    Article  PubMed  Google Scholar 

  17. Jones GE (1949) Some newer aspects of the management of infertility. J Am Med Assoc 141:1123–1129

    Article  CAS  PubMed  Google Scholar 

  18. Jordan J, Craig K, Clifton DK et al (1994) Luteal phase defect: the sensitivity and specificity of diagnostic methods in common clinical use. Fertil Steril 62:54–62

    Article  CAS  PubMed  Google Scholar 

  19. Malcolm CE, Cumming DC (2003) Does anovulation exist in eumenorrheic women? Obstet Gynecol 102:317–318

    PubMed  Google Scholar 

  20. Murray MJ, Meyer WR, Zaino RJ et al (2004) A critical analysis of the accuracy, reproducibility, and clinical utility of histologic endometrial dating in fertile women. Fertil Steril 81:1333–1343

    Article  PubMed  Google Scholar 

  21. Nawroth F, Ludwig M (2008) What can we expect if we measure hormones in eumenorrhoeic infertile patients? Reprod Biomed Online 16:621–626

    Article  CAS  PubMed  Google Scholar 

  22. Neumann K, Depenbusch M, Schultze-Mosgau A et al (2020) Characterization of early pregnancy placental progesterone production by use of dydrogesterone in programmed frozen-thawed embryo transfer cycles. Reprod Biomed Online 40:743–751

    Article  CAS  PubMed  Google Scholar 

  23. Niswender GD, Juengel JL, Silva PJ et al (2000) Mechanisms controlling the function and life span of the corpus luteum. Physiol Rev 80:1–29

    Article  CAS  PubMed  Google Scholar 

  24. Noyes RW, Hertig AT, Rock J (1950) Dating the endometrial biopsy. Fertil Steril 1:3–9

    Article  Google Scholar 

  25. Practice Committee of the American Society for Reproductive Medicine (2015) Current clinical irrelevance of luteal phase deficiency: a committee opinion. Fertil Steril 103:e27–32

    Google Scholar 

  26. Saccone G, Schoen C, Franasiak JM et al (2017) Supplementation with progestogens in the first trimester of pregnancy to prevent miscarriage in women with unexplained recurrent miscarriage: a systematic review and meta-analysis of randomized, controlled trials. Fertil Steril 107:430–438.e3

    Article  CAS  PubMed  Google Scholar 

  27. Simon C, Gomez C, Cabanillas S et al (2020) A 5‑year multicentre randomized controlled trial comparing personalized, frozen and fresh blastocyst transfer in IVF. Reprod Biomed Online 41:402–415

    Article  CAS  PubMed  Google Scholar 

  28. Sonntag B (2016) Zyklusstörungen. Gynäkologe 49:357–372

    Article  CAS  Google Scholar 

  29. Sonntag B (2020) Beurteilung und Therapie der Lutealphase. In: Diedrich K, Ludwig M, Griesinger G (Hrsg) Reproduktionsmedizin. Springer, Berlin, Heidelberg, S 71–78

    Chapter  Google Scholar 

  30. Sonntag B, Ludwig M (2012) An integrated view on the luteal phase: diagnosis and treatment in subfertility. Clin Endocrinol (Oxf) 77:500–507

    Article  Google Scholar 

  31. Soules MR, Mclachlan RI, Ek M et al (1989) Luteal phase deficiency: characterization of reproductive hormones over the menstrual cycle. J Clin Endocrinol Metab 69:804–812

    Article  CAS  PubMed  Google Scholar 

  32. Stephenson MD, Mcqueen D, Winter M et al (2017) Luteal start vaginal micronized progesterone improves pregnancy success in women with recurrent pregnancy loss. Fertil Steril 107:684–690.e2

    Article  CAS  PubMed  Google Scholar 

  33. Szekeres-Bartho J, Balasch J (2008) Progestagen therapy for recurrent miscarriage. Hum Reprod Update 14:27–35

    Article  PubMed  Google Scholar 

  34. Toth B, Rösner S, Thöne C et al (2010) Lutealphaseninsuffizienz. Schwächelt der Gelbkörper wirklich? J Gynäkol Endokrinol 8:105–111

    Article  Google Scholar 

  35. Usadi RS, Groll JM, Lessey BA et al (2008) Endometrial development and function in experimentally induced luteal phase deficiency. J Clin Endocrinol Metab 93:4058–4064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Young SL, Savaris RF, Lessey BA et al (2017) Effect of randomized serum progesterone concentration on secretory endometrial histologic development and gene expression. Hum Reprod 32:1903–1914

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Barbara Sonntag.

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G. Griesinger, Lübeck

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Sonntag, B. Lutealphaseninsuffizienz bei Kinderwunsch. Gynäkologische Endokrinologie 19, 99–104 (2021). https://doi.org/10.1007/s10304-020-00367-2

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  • DOI: https://doi.org/10.1007/s10304-020-00367-2

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