Serum anti-Mullerian hormon seviyesi ve antral follikül sayısının stimule edilmemiş menstruel siklustaki değişiminin saptanması

Abstract

Amaç: Çalışmada düzenli menstruel siklusu olan sağlıklı hastalarda, doğal siklusta serum anti-Mullerian hormon değerlerinin ve antral follikül sayımının, intra-menstruel değişiminin saptanması amaçlanmıştır. Gereç ve Yöntemler: Çalışmaya menstruel siklusu düzenli olan, sistemik hastalık ve geçirilmiş over cerrahi öyküsü olmayan, son iki ay içinde hormonal kontraseptif preparat kullanmamış olan 50 sağlıklı kadın dahil edilmiştir. Serum anti-Mullerian hormon seviyeleri ve antral follikül sayısı stimüle edilmemiş aynı siklus içerisinde erken folliküler faz, geç folliküler faz ve luteal fazda olmak üzere üç kez değerlendirilmiştir. Yaş gruplarına göre serum anti-Mullerian hormon seviyelerinin karşılaştırılması amacıyla da hastalar genç (<35 yaş) ve ileri yaş (35 yaş) olmak üzere iki gruba ayrılmıştır. Bulgular: Hastaların yaş ortalaması 30.8, vücut kitle indeksi ortalaması 23.4 kg/m2 ve ortalama siklus uzunluğu 28.5 gün olarak bulunmuştur. Aynı menstruel siklusta erken folliküler faz, geç folliküler faz ve luteal faz olmak üzere üç kez değerlendirilen serum anti-Mullerian hormon seviyesi ortalaması 2.66 ng/dl ve ortalama antral follikül sayısı 17.4 olarak saptanmıştır. En yüksek serum anti-Mullerian hormon seviyesi ve antral follikül sayısı geç folliküler fazda bulunmuştur ve bu fark antral follikül sayısında olmasa da serum anti-Mullerian hormon seviyesi karşılaştırmasında istatistiksel olarak anlamlı bulunmuştur. (p=0.307, p= 0.044). Serum anti-Mullerian hormon variabilitesi genç grupta, ileri yaş gruba kıyasla daha fazla olarak saptanmış olup istatistiksel olarak anlamlı bulunmuştur. (0.241 vs 0.132, p=0.011) Sonuç: Serum anti-Mullerian hormon seviyeleri menstruel siklus içinde dalgalanmalar göstermekte olup, en yüksek serum anti-Mullerian hormon seviyesi geç folliküler fazda saptanmıştır. Antral follikül sayımı menstruel siklus boyunca sabit kalmıştır.

Keywords

• Anti-Mullerian hormon
• menstruel siklus
• over rezervi
• antral follikül sayısı
• intra-siklik variabilite

Variability of serum anti-Mullerian hormone level and antral follicle count in an unstimulated menstrual cycle

Abstract

Aim: To evaluate the variability of anti-Mullerian hormone (AMH) and antral follicle count (AFC) in an unstimulated menstrual cycle. Materials and Method: The study was designed on 50 women who had regular menstrual cycles and did not have any systemic disease or previous ovarian surgery. Serum AMH levels and antral follicle counts of all participants were evaluated three times in the same menstrual cycle in the early and late follicular phase and luteal phase. To evaluate the intracyclic AMH fluctuation according to age, participants were divided into two groups; younger (<35 years) and older (35 years old). Results: The mean age of the participants was 30.8, the mean BMI was 23.4 kg/m2, and the mean menstrual cycle duration was 28.5 days. Mean AMH values evaluated at three different times in the menstrual cycle, early follicular, late follicular, and luteal phase, were 2.66 ng/dl and mean AFC 17.4. The highest mean AMH level and AFC were detected in the late follicular phase and this was statistically significant for AMH level but not for AFC (p= 0.044, p=0.307, respectively). The intracyclic fluctuation of AMH was greater in the younger patient group. The coefficient of variation was 0.241 in the younger patient group, and 0.132 in the older patient group. (p=0.011) Conclusion: Serum AMH levels fluctuate throughout the menstrual cycle and the highest serum AMH level was detected in the late follicular phase. AFC remained stable throughout the cycle.

Keywords

• Anti-Mullerian hormone
• menstrual cycle
• ovarian reserve
• antral follicle count
• intra-cycle variability

References

1. Reference 1. Sauer MV. Reproduction at an advanced maternal age and maternal health. 2015;103(5):1136-43. doi: 10.1016/j.fertnstert.2015.03.004.
2. Reference 2. Dolmans MM, Donnez J. Fertility preservation in women for medical and social reasons: Oocytes vs ovarian tissue. Best Pract Res Clin Obstet Gynaecol. 2021;70:63–80. doi: 10.1016/J.BPOBGYN.2020.06.011. Cited: in: PMID: 32800711.
3. Reference 3. Korte E, Schilling R, Balcerek M, Byrne J, DIrksen U, Herrmann G, et al. Fertility-Related Wishes and Concerns of Adolescent Cancer Patients and Their Parents. https://home.liebertpub.com/jayao. 2020;9(1):55–62. doi: 10.1089/JAYAO.2019.0064. Cited: in: PMID: 31621493.
4. Reference 4. Loh JS, Maheshwari A. Anti-Müllerian hormone—is it a crystal ball for predicting ovarian ageing? Hum Reprod. 2011;26(11):2925–2932. doi: 10.1093/HUMREP/DER271. Cited: in: PMID: 21849297.
5. Reference 5. Fleming R, Seifer DB, Frattarelli JL, Ruman J. Assessing ovarian response: antral follicle count versus anti-Müllerian hormone. Reprod Biomed Online. 2015;31(4):486-96. doi: 10.1016/j.rbmo.2015.06.015.
6. Reference 6. Sighinolfi G, Grisendi V, La Marca A. How to personalize ovarian stimulation in clinical practice. J Turk-Ger Gynecol Assoc. 2017;18(3):148-153. doi: 10.4274/jtgga.2017.0058.
7. Reference 7. Cakmak H, Rosen MP. Random-start ovarian stimulation in patients with cancer. Curr Opin Obstet Gynecol. 2015;27(3):215–221. doi: 10.1097/GCO.0000000000000180. Cited: in: PMID: 25919235.
8. Reference 8. Galati G, Serra N, Ciaffaglione M, Pinna M, Reschini M, Pisaturo V, et al. Folliculogenesis in random start protocols for oocytes cryopreservation: quantitative and qualitative aspects. Reprod Sci. 2022; doi: 10.1007/s43032-022-00945-8.

9. Reference 9. Alsbjerg B, Haahr T, Elbaek HO, Laursen R, Povlsen BB, Humaidan P. Dual stimulation using corifollitropin alfa in 54 Bologna criteria poor ovarian responders – a case series. Reprod Biomed Online. 2019;38(5):677–682. doi: 10.1016/J.RBMO.2019.01.007. Cited: in: PMID: 30795977.
10. Reference 10. La Marca A, Malmusi S, Giulini S, Tamaro LF, Orvieto R, Levratti P, et al. Anti-Müllerian hormone plasma levels in spontaneous menstrual cycle and during treatment with FSH to induce ovulation. Hum Reprod. 2004;19(12):2738–2741. doi: 10.1093/humrep/deh508.
11. Reference 11. La Marca A, Stabile G, Carducci Artenisio A, Volpe A. Serum anti-Mullerian hormone throughout the human menstrual cycle. Hum Reprod. 2006;21(12):3103-7. doi: 10.1093/humrep/del291.
12. Reference 12. Hadlow N, Longhurst K, McClements A, Natalwala J, Brown SJ, Matson PL. Variation in antimüllerian hormone concentration during the menstrual cycle may change the clinical classification of the ovarian response. Fertil Steril. 2013;99(6):1791–1797. doi: 10.1016/j.fertnstert.2013.01.132.
13. Reference 13. Wunder DM, Bersinger NA, Yared M, Kretschmer R, Birkhäuser MH. Statistically significant changes of antimüllerian hormone and inhibin levels during the physiologic menstrual cycle in reproductive age women. Fertil Steril. 2008;89(4):927-33 doi: 10.1016/j.fertnstert.2007.04.054.
14. Reference 14. Gorkem U, Kucukler FK, Togrul C, Gungor T. Anti-Müllerian hormone exhibits a great variation in infertile women with different ovarian reserve patterns. Aust N Z J Obstet Gynaecol. 2017;57(4):464–468. doi: 10.1111/AJO.12625. Cited: in: : PMID: 28419409.
15. Reference 15. Gorkem U, Togrul C. Is There a Need to Alter the Timing of Anti-Müllerian Hormone Measurement during the Menstrual Cycle? Geburtshilfe Frauenheilkd. 2019;79(7):731–737. doi: 10.1055/a-0840-3817.
16. Reference 16. Sowers M, McConnell D, Gast K, Zheng H, Nan B, McCarthy JD, Randolph JF. Anti-Müllerian hormone and inhibin B variability during normal menstrual cycles. Fertil Steril. 2010;94(4):1482-1486. doi: 10.1016/j.fertnstert.2009.07.1674.
17. Reference 17. Hehenkamp WJK, Looman CWN, Themmen APN, De Jong FH, Te Velde ER, Broekmans FJM. Anti-Müllerian hormone levels in the spontaneous menstrual cycle do not show substantial fluctuation. J Clin Endocrinol Metab. 2006;91(10):4057-63 doi: 10.1210/jc.2006-0331.
18. Reference 18. Overbeek A, Broekmans FJ, Hehenkamp WJ, Wijdeveld ME, Van Disseldorp J, Van Dulmen-Den Broeder E, et al. Intra-cycle fluctuations of anti-Müllerian hormone in normal women with a regular cycle: a re-analysis. Reprod Biomed Online. 2012;24(6):664–669. doi: 10.1016/J.RBMO.2012.02.023. Cited: in: : PMID: 22503280.
19. Reference 19. La Marca A, Grisendi V, Griesinger G. How much does AMH really vary in normal women? Int J Endocrinol. 2013;2013:959487. doi: 10.1155/2013/959487.
20. Reference 20. Van Disseldorp J, Lambalk CB, Kwee J, Looman CWN, Eijkemans MJC, Fauser BC, et al. Comparison of inter-and intra-cycle variability of anti-Müllerian hormone and antral follicle counts. Hum Reprod. 2010;25(1):221–227. doi: 10.1093/humrep/dep366.
21. Reference 21. Depmann M, van Disseldorp J, Broer SL, Eijkemans MJC, Laven JSE, Visser JA, et al. Fluctuations in anti-Müllerian hormone levels throughout the menstrual cycle parallel fluctuations in the antral follicle count: a cohort study. Acta Obstet Gynecol Scand. 2016;95(7):820–828. doi: 10.1111/aogs.12886.
22. Reference 22. Deb S, Campbell BK, Clewes JS, Pincott‐Allen C, Raine‐Fenning NJ. Intracycle variation in number of antral follicles stratified by size and in endocrine markers of ovarian reserve in women with normal ovulatory menstrual cycles. Ultrasound Obstet Gynecol. 2013;41(2):216–222. doi: 10.1002/uog.11226.
23. Reference 23. Mavrelos D, Al Chami A, Talaulikar V, Burt E, Webber L, Ploubidis G, et al. Variation in antral follicle counts at different times in the menstrual cycle: does it matter? Reprod Biomed Online. 2016;33(2):174–179. doi: 10.1016/j.rbmo.2016.04.012.