Skip to main content
SpringerLink
Log in

Hyperandrogenemia and ovarian reserve in patients with Mayer–Rokitansky–Küster–Hauser syndrome type 1 and 2: potential influences on ovarian stimulation

  • Gynecologic Endocrinology and Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

This study aimed to analyze the hormone profiles, to detect the rate of hyperandrogenemia and to investigate the potential effect of Mayer–Rokitansky–Küster–Hauser syndrome (MRKHS) on ovarian reserve, as reflected by the serum Anti-Mullerian hormone (AMH) levels. Clinical implications were analyzed by including our own experiences with three patients after ovarian stimulation in preparation for uterus transplantation.

Methods

Serum samples of 100 patients with MRKHS (50 patients with MRKHS type 1 and 50 with type 2) were analyzed and compared to 50 individually age-matched healthy controls. Blood samples for hormone analyses were collected routinely during the clinical visit.

Results

The mean age was 20.0 years for MRKHS type 1, MRKHS type 2 and healthy controls. Compared to healthy controls, there was no significant difference in AMH values in the MRKH patients. As shown in previous studies, the proportion of hyperandrogenemia without clinical symptoms was significantly higher in MRKHS type 1 (52%; p < 0.001) and type 2 (56%; p < 0.001) patients when compared to age-matched controls. In preparation for uterus transplantation, three patients were stimulated with FSH/hMG for mean 14.2 days and the mean number of aspirated oocytes was 13.2 (3–22), while 8.3 (2–10) oocytes could be fertilized and cryopreserved. The mean fertilization rate was 51.2% (30–67%).

Conclusion

The rate of hyperandrogenemia was significantly higher in MRKH patients compared to healthy age-matched controls. Though, ovarian reserve (AMH level) was not reduced compared to controls. Future studies are needed to identify optimal ovarian stimulation protocols as well as to implement a systematic multicenter reporting system.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Aittomaki K, Eroila H, Kajanoja P (2001) A population-based study of the incidence of Mullerian aplasia in Finland. Fertil Steril 76:624–625

    Article  CAS  PubMed  Google Scholar 

  2. Anonymous (2016) Deutsches IVF Register (DIR), Jahrbuch 2015. modif. Reprint from J Reproduktionsmed Endokrinol 13

  3. Balen A (2004) The pathophysiology of polycystic ovary syndrome: trying to understand PCOS and its endocrinology. Best Pract Res Clin Obstet Gynaecol 18:685–706

    Article  PubMed  Google Scholar 

  4. Bernardini L, Gimelli S, Gervasini C et al (2009) Recurrent microdeletion at 17q12 as a cause of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome: two case reports. Orphanet J Rare Dis 4:25

    Article  PubMed  PubMed Central  Google Scholar 

  5. Biason-Lauber A, De Filippo G, Konrad D et al (2007) WNT4 deficiency–a clinical phenotype distinct from the classic Mayer-Rokitansky-Kuster-Hauser syndrome: a case report. Hum Reprod 22:224–229

    Article  CAS  PubMed  Google Scholar 

  6. Biason-Lauber A, Konrad D, Navratil F et al (2004) A WNT4 mutation associated with Mullerian-duct regression and virilization in a 46, XX woman. N Engl J Med 351:792–798

    Article  CAS  PubMed  Google Scholar 

  7. Brannstrom M, Bokstrom H, Dahm-Kahler P et al (2016) One uterus bridging three generations: first live birth after mother-to-daughter uterus transplantation. Fertil Steril 106:261–266

    Article  PubMed  Google Scholar 

  8. Brannstrom M, Johannesson L, Bokstrom H et al (2015) Livebirth after uterus transplantation. Lancet 385:607–616

    Article  PubMed  Google Scholar 

  9. Brannstrom M, Johannesson L, Bokstrom H et al (2015) Livebirth after uterus transplantation. Lancet 385:607–616

    Article  PubMed  Google Scholar 

  10. Brucker SY, Gegusch M, Zubke W et al (2008) Neovagina creation in vaginal agenesis: development of a new laparoscopic Vecchietti-based procedure and optimized instruments in a prospective comparative interventional study in 101 patients. Fertil Steril 90:1940–1952

    Article  PubMed  Google Scholar 

  11. Carranza-Lira S, Forbin K, Martinez-Chequer JC (1999) Rokitansky syndrome and MURCS association—clinical features and basis for diagnosis. Int J Fertil Womens Med 44:250–255

    CAS  PubMed  Google Scholar 

  12. Chen MJ, Wei SY, Yang WS et al (2015) Concurrent exome-targeted next-generation sequencing and single nucleotide polymorphism array to identify the causative genetic aberrations of isolated Mayer-Rokitansky-Kuster-Hauser syndrome. Hum Reprod 30:1732–1742

    Article  CAS  PubMed  Google Scholar 

  13. Cicinelli E, Einer-Jensen N, Cignarelli M et al (2004) Preferential transfer of endogenous ovarian steroid hormones to the uterus during both the follicular and luteal phases. Hum Reprod 19:2001–2004

    Article  CAS  PubMed  Google Scholar 

  14. Folch M, Pigem I, Konje JC (2000) Mullerian agenesis: etiology, diagnosis, and management. Obstet Gynecol Surv 55:644–649

    Article  CAS  PubMed  Google Scholar 

  15. Fraser IS, Baird DT, Hobson BM et al (1973) Cyclical ovarian function in women with congenital absence of the uterus and vagina. J Clin Endocrinol Metab 36:634–637

    Article  CAS  PubMed  Google Scholar 

  16. Friedler S, Grin L, Liberti G et al (2016) The reproductive potential of patients with Mayer-Rokitansky-Kuster-Hauser syndrome using gestational surrogacy: a systematic review. Reprod Biomed Online 32:54–61

    Article  PubMed  Google Scholar 

  17. Hall-Craggs MA, Kirkham A, Creighton SM (2013) Renal and urological abnormalities occurring with Mullerian anomalies. J Pediatr Urol 9:27–32

    Article  PubMed  Google Scholar 

  18. Hansen KR, Knowlton NS, Thyer AC et al (2008) A new model of reproductive aging: the decline in ovarian non-growing follicle number from birth to menopause. Hum Reprod 23:699–708

    Article  PubMed  Google Scholar 

  19. Herlin M, Bjorn AM, Rasmussen M et al (2016) Prevalence and patient characteristics of Mayer-Rokitansky-Kuster-Hauser syndrome: a nationwide registry-based study. Hum Reprod 31:2384–2390

    Article  PubMed  Google Scholar 

  20. Jb B (1959) Preliminary observation on urinary oestrogen excretion in certain gynaecological disorders. J Obstet Gynaecol Br Commonw 66:177–211

    Article  Google Scholar 

  21. Kallio S, Puurunen J, Ruokonen A et al (2013) Antimullerian hormone levels decrease in women using combined contraception independently of administration route. Fertil Steril 99:1305–1310

    Article  CAS  PubMed  Google Scholar 

  22. Kim JY, Tfayli H, Michaliszyn SF et al (2017) Anti-Mullerian Hormone in Obese Adolescent Girls With Polycystic Ovary Syndrome. J Adolesc Health 60:333–339

    Article  PubMed  Google Scholar 

  23. Ledig S, Schippert C, Strick R et al (2011) Recurrent aberrations identified by array-CGH in patients with Mayer-Rokitansky-Kuster-Hauser syndrome. Fertil Steril 95:1589–1594

    Article  CAS  PubMed  Google Scholar 

  24. Morcel K, Watrin T, Pasquier L et al (2011) Utero-vaginal aplasia (Mayer-Rokitansky-Kuster-Hauser syndrome) associated with deletions in known DiGeorge or DiGeorge-like loci. Orphanet J Rare Dis 6:9

    Article  PubMed  PubMed Central  Google Scholar 

  25. Nik-Zainal S, Strick R, Storer M et al (2011) High incidence of recurrent copy number variants in patients with isolated and syndromic Mullerian aplasia. J Med Genet 48:197–204

    Article  PubMed  PubMed Central  Google Scholar 

  26. Oppelt P, Renner SP, Kellermann A et al (2006) Clinical aspects of Mayer-Rokitansky-Kuester-Hauser syndrome: recommendations for clinical diagnosis and staging. Hum Reprod 21:792–797

    Article  PubMed  Google Scholar 

  27. Oppelt P, Strissel PL, Kellermann A et al (2005) DNA sequence variations of the entire anti-Mullerian hormone (AMH) gene promoter and AMH protein expression in patients with the Mayer-Rokitanski-Kuster-Hauser syndrome. Hum Reprod 20:149–157

    Article  CAS  PubMed  Google Scholar 

  28. Oppelt PG, Mueller A, Stephan L et al. (2017) Hyperandrogenemia and high prolactin in congenital utero-vaginal aplasia patients. Reproduction

  29. Ozekinci M, Erman Akar M, Senol Y et al (2015) Comparison of markers of ovarian reserve between patients with complete mullerian agenesis and age-matched fertile and infertile controls. Fertil Steril 104:176–179

    Article  PubMed  Google Scholar 

  30. Philibert P, Biason-Lauber A, Gueorguieva I et al (2011) Molecular analysis of WNT4 gene in four adolescent girls with mullerian duct abnormality and hyperandrogenism (atypical Mayer-Rokitansky-Kuster-Hauser syndrome). Fertil Steril 95:2683–2686

    Article  CAS  PubMed  Google Scholar 

  31. Philibert P, Biason-Lauber A, Rouzier R et al (2008) Identification and functional analysis of a new WNT4 gene mutation among 28 adolescent girls with primary amenorrhea and mullerian duct abnormalities: a French collaborative study. J Clin Endocrinol Metab 93:895–900

    Article  CAS  PubMed  Google Scholar 

  32. Rall K, Conzelmann G, Schaffeler N et al (2014) Acne and PCOS are less frequent in women with Mayer-Rokitansky-Kuster-Hauser syndrome despite a high rate of hyperandrogenemia: a cross-sectional study. Reprod Biol Endocrinol 12:23

    Article  PubMed  PubMed Central  Google Scholar 

  33. Raziel A, Friedler S, Gidoni Y et al (2012) Surrogate in vitro fertilization outcome in typical and atypical forms of Mayer-Rokitansky-Kuster-Hauser syndrome. Hum Reprod 27:126–130

    Article  CAS  PubMed  Google Scholar 

  34. Sandbacka M, Halttunen M, Jokimaa V et al (2011) Evaluation of SHOX copy number variations in patients with Mullerian aplasia. Orphanet J Rare Dis 6:53

    Article  PubMed  PubMed Central  Google Scholar 

  35. Sowers M, Mcconnell D, Gast K et al (2010) Anti-Mullerian hormone and inhibin B variability during normal menstrual cycles. Fertil Steril 94:1482–1486

    Article  CAS  PubMed  Google Scholar 

  36. Strissel PL, Oppelt P, Cupisti S et al (2009) Assessment of pituitary and steroid hormones and members of the TGF-beta superfamily for ovarian function in patients with congenital uterus and vaginal aplasia (MRKH syndrome). Horm Metab Res 41:408–413

    Article  CAS  PubMed  Google Scholar 

  37. Strubbe EH, Willemsen WN, Lemmens JA et al (1993) Mayer-Rokitansky-Kuster-Hauser syndrome: distinction between two forms based on excretory urographic, sonographic, and laparoscopic findings. AJR Am J Roentgenol 160:331–334

    Article  CAS  PubMed  Google Scholar 

  38. Sultan C, Biason-Lauber A, Philibert P (2009) Mayer-Rokitansky-Kuster-Hauser syndrome: recent clinical and genetic findings. Gynecol Endocrinol 25:8–11

    Article  CAS  PubMed  Google Scholar 

  39. Ugur M, Karakaya S, Zorlu G et al (1995) Polycystic ovaries in association with mullerian anomalies. Eur J Obstet Gynecol Reprod Biol 62:57–59

    Article  CAS  PubMed  Google Scholar 

  40. Verma AK, Rajbhar S, Mishra J et al (2016) Anti-mullerian hormone: a marker of ovarian reserve and its association with polycystic ovarian syndrome. J Clin Diagn Res 10:QC10–QC12

    PubMed  PubMed Central  Google Scholar 

  41. Visser JA, De Jong FH, Laven JS et al (2006) Anti-Mullerian hormone: a new marker for ovarian function. Reproduction 131:1–9

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank all patients who participated in this study and Sabine Hofmeister for her help with the biobank. The present data/results were part of the MD thesis work of Ludmila Jurow (L. Jurow, unpublished thesis work). She fully agreed to include the present data.

Funding

There was no funding for this study.

Author information

Authors and Affiliations

  1. Department of Women’s Health, Center for Rare Female Genital Malformations, Women’s University Hospital, Tuebingen University Hospital, Calwerstr. 7, 72076, Tuebingen, Germany

    Melanie Henes, Florin Andrei Taran, Markus Huebner, Sara Yvonne Brucker & Kristin Katharina Rall

  2. Department of Women’s Health, Research Center for Women’s Health, University Tuebingen, Calwerstr. 7, 72076, Tuebingen, Germany

    Ludmila Jurow, Birgitt Schoenfisch, Harald Seeger & Sara Yvonne Brucker

  3. Department of Internal Medicine, Central Laboratory, Tuebingen University Hospital, Otfried-Müller-Str. 10, 72076, Tuebingen, Germany

    Andreas Peter

Authors
  1. Melanie Henes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ludmila Jurow
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andreas Peter
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Birgitt Schoenfisch
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Florin Andrei Taran
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Markus Huebner
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Harald Seeger
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sara Yvonne Brucker
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kristin Katharina Rall
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MH: protocol/project development, data analysis, manuscript writing/editing. KR: protocol/project development, data collection, data analysis, manuscript writing/editing. LJ: data collection, data analysis. AP: hormone analyses. BS: age-matching, data analysis (statistics). FAT: critical revision of manuscript. MH: critical revision of manuscript. HS: archiving of blood samples, critical revision of manuscript. SYB: data collection, critical revision of manuscript.

Corresponding author

Correspondence to Kristin Katharina Rall.

Ethics declarations

Conflict of interest

The authors state that there are no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Henes, M., Jurow, L., Peter, A. et al. Hyperandrogenemia and ovarian reserve in patients with Mayer–Rokitansky–Küster–Hauser syndrome type 1 and 2: potential influences on ovarian stimulation. Arch Gynecol Obstet 297, 513–520 (2018). https://doi.org/10.1007/s00404-017-4596-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-017-4596-1

Keywords

Search

Navigation