{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T15:33:41Z","timestamp":1791992021713,"version":"4.4.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T00:00:00Z","timestamp":1574985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>STUDY QUESTION<\/jats:title>\n                  <jats:p>How do anti-M\u00fcllerian hormone (AMH) serum concentrations and follicle densities (FDs) change with age and disease and what are the implications for fertility preservation?<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>SUMMARY ANSWER<\/jats:title>\n                  <jats:p>AMH concentrations and FD do not correlate in young women, and AMH but not FD is reduced in some diseases, limiting the value of AMH as a predictive parameter of ovarian tissue transplantation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                  <jats:p>AMH is widely used as a parameter to estimate the ovarian reserve. However, the reliability of AMH to predict total number of follicles and the FD is questionable. Women with lymphoma and leukaemia have been shown to have reduced AMH concentrations, but it is unknown if the FD is also reduced. In fertility preservation it is essential to estimate the correct total number of follicles and the FD, as ovarian tissue should only be cryopreserved if ovarian reserve is high. Furthermore, the amount of tissue to be transplanted should be based on the estimation of the real FD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                  <jats:p>This retrospective observational study included 830 women (mean\u2009\u00b1\u2009SD age, 28.2\u2009\u00b1\u20096.81\u00a0years; range, 4\u201343\u00a0years) with malignant (n\u00a0=\u2009806) and benign (n\u00a0=\u200924) diseases who cryopreserved tissue in a single centre as part of a national fertility preservation programme. Females with ovarian surgery or known predispositions for a reduced ovarian reserve were excluded. AMH concentrations and FD were evaluated from March 2011 to September 2016.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                  <jats:p>AMH concentrations were analysed before gonadotoxic therapies. Standardized biopsies, obtained from different areas of ovarian cortex, were collected. FD was analysed after tissue digestion and calcein staining and was expressed as average number of primordial and primary follicles count per 3\u00a0mm biopsy and per cubic millimeter tissue. AMH concentrations and FD were analysed in relation to age and diagnosis group. Both parameters were age adjusted, and associations between the different diagnosis groups and AMH versus FD were assessed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                  <jats:p>Mean\u2009\u00b1\u2009SD AMH concentration was 3.1\u2009\u00b1\u20092.81\u00a0g\/ml, mean FD per 3\u00a0mm biopsy was 137\u2009\u00b1\u2009173.9 and 19.4\u2009\u00b1\u200924.60 per mm3. Maximum AMH concentrations were found in children and teenagers at the age of 6\u201310\u00a0years (5.71\u00a0ng\/ml) and in adults at the age of 21\u201325\u00a0years (3.33\u00a0ng\/ml). FD was highest in young children up to an age of 15\u00a0years and decreased with increasing age. AMH and FD were not correlated in women \u226420\u00a0years and weakly to moderately correlated in women 21\u201340\u00a0years (r\u00a0=\u20090.24\u20130.39). Age-adjusted correlations between AMH and FD were demonstrated in several diagnosis groups such as breast cancer, leukaemia, sarcoma, gastrointestinal cancer and gynaecological cancer but not in the groups exhibiting Hodgkin\u2019s and non-Hodgkin\u2019s lymphoma, cerebral cancer, other types of malignancies and other types of benign diseases. Further statistical analysis supported the finding that, in some diagnosis groups such as Hodgkin\u2019s lymphoma and in gynaecological cancer, AMH concentrations but not FDs are reduced, questioning the prognostic accuracy of AMH for the FD in these diseases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                  <jats:p>Even though biopsies were taken from different sites, heterogenous distribution of follicles might have had some effect on the accuracy of the analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WIDER IMPLICATION OF THE FINDINGS<\/jats:title>\n                  <jats:p>AMH should be used with care to estimate the total ovarian reserve and FD of cancer patients in young women in some diseases. Therefore, calculating the amount of ovarian tissue to be transplanted based solely on AMH might be inaccurate whereas FD might be a better parameter.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                  <jats:p>The study did not receive any exterior funding.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/humrep\/dez215","type":"journal-article","created":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T12:12:21Z","timestamp":1574943141000},"page":"2513-2522","source":"Crossref","is-referenced-by-count":47,"title":["Serum anti-M\u00fcllerian hormone concentration and follicle density throughout reproductive life and in different diseases\u2014implications in fertility preservation"],"prefix":"10.1093","volume":"34","author":[{"given":"J","family":"Liebenthron","sequence":"first","affiliation":[{"name":"UniCareD, University Cryobank for Assisted Reproductive Medicine and Fertility Protection at UniKiD D\u00fcsseldorf, University Hospital D\u00fcsseldorf, Moorenstr. 5, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Reinsberg","sequence":"first","affiliation":[{"name":"Department of Gynaecological Endocrinology and Reproductive Medicine, University Clinic Bonn, Sigmund-Freud-Str. 25, 53125 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"van der Ven","sequence":"first","affiliation":[{"name":"Ambulatory Healthcare Centre for Gynaecological Endocrinology and Reproductive Medicine Bonn (MVZ f\u00fcr Frauenheilkunde und IvF-Medizin Bonn GbR), Godesberger Allee 64, 53175 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Saenger","sequence":"first","affiliation":[{"name":"Department of Gynaecological Endocrinology and Reproductive Medicine, University Clinic Bonn, Sigmund-Freud-Str. 25, 53125 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J-S","family":"Kruessel","sequence":"first","affiliation":[{"name":"UniCareD, University Cryobank for Assisted Reproductive Medicine and Fertility Protection at UniKiD D\u00fcsseldorf, University Hospital D\u00fcsseldorf, Moorenstr. 5, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"von Wolff","sequence":"first","affiliation":[{"name":"University Women\u2019s Hospital, Division of Gynaecological Endocrinology and Reproductive Medicine, Friedb\u00fchlstrasse 19, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,11,29]]},"reference":[{"key":"2020032810045921700_ref1","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1007\/s10815-014-0239-7","article-title":"Efficacy of ovarian tissue cryopreservation in a major European center","volume":"31","author":"Bastings","year":"2014","journal-title":"J Assist Reprod Genet"},{"key":"2020032810045921700_ref2","first-page":"1","article-title":"Concept paper on the technique of cryopreservation, removal and transplantation of ovarian tissue for fertility preservation. GebFra science review","volume":"78","author":"Beckmann","year":"2018","journal-title":"Geburtsh Frauenheilk"},{"key":"2020032810045921700_ref3","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1093\/humupd\/dml034","article-title":"A systematic review of tests predicting ovarian reserve and IVF outcome","volume":"12","author":"Broekmans","year":"2006","journal-title":"Hum Reprod Update"},{"key":"2020032810045921700_ref4","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1210\/jc.2011-3180","article-title":"Anti-M\u00fcllerian hormone is a marker of gonadotoxicity in pre- and postpubertal girls treated for cancer: a prospective study","volume":"97","author":"Brougham","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"2020032810045921700_ref5","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1097\/GCO.0b013e3283384911","article-title":"The role of anti-M\u00fcllerian hormone assessment in assisted reproductive technology outcome","volume":"22","author":"Broer","year":"2010","journal-title":"Curr Opin Obstet Gynecol"},{"key":"2020032810045921700_ref6","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1210\/jc.2010-2776","article-title":"Anti-mullerian hormone predicts menopause: a long-term follow-up study in normoovulatory women","volume":"96","author":"Broer","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"2020032810045921700_ref7","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.fertnstert.2013.04.024","article-title":"Prediction of an excessive response in in vitro fertilization from patient characteristics and ovarian reserve tests and comparison in subgroups: an individual patient data meta-analysis","volume":"100","author":"Broer","year":"2013","journal-title":"Fertil Steril"},{"key":"2020032810045921700_ref8","doi-asserted-by":"crossref","first-page":"583","DOI":"10.2214\/ajr.160.3.8430559","article-title":"Normal ovaries in neonates and infants: a sonographic study of 77 patients 1 day to 24 months old","volume":"160","author":"Cohen","year":"1993","journal-title":"Am J Roentgenol"},{"key":"2020032810045921700_ref9","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1210\/jc.2012-4228","article-title":"The relationship between anti-M\u00fcllerian hormone in women receiving fertility assessments and age at menopause in subfertile women: evidence from large population studies","volume":"98","author":"D\u00f3lleman","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"2020032810045921700_ref10","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1016\/j.fertnstert.2016.09.001","article-title":"Effect of first line cancer treatment on the ovarian reserve and follicular density in girls under the age of 18 years","volume":"106","author":"El Issaoui","year":"2016","journal-title":"Fertil Steril"},{"key":"2020032810045921700_ref11","volume-title":"Atlas of Ultrasound Measurements","author":"Goldberg","year":"2006"},{"key":"2020032810045921700_ref12","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1093\/humrep\/dem081","article-title":"The number of small antral follicles (2-6 mm) determines the outcome of endocrine ovarian reserve tests in a subfertile population","volume":"22","author":"Haadsma","year":"2007","journal-title":"Hum Reprod"},{"key":"2020032810045921700_ref13","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.fertnstert.2010.04.006","article-title":"Correlation of ovarian reserve tests with histologically determined primordial follicle number","volume":"95","author":"Hansen","year":"2011","journal-title":"Fertil Steril"},{"key":"2020032810045921700_ref14","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ejogrb.2017.04.029","article-title":"Age-independent anti-M\u00fcllerian hormone (AMH) standard deviation scores to estimate ovarian function","volume":"213","author":"Helden","year":"2017","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"2020032810045921700_ref15","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1093\/rheumatology\/kev124","article-title":"Ovarian reserve alterations in premenopausal women with chronic inflammatory rheumatic diseases: impact of rheumatoid arthritis, Beh\u00e7et's disease and spondyloarthritis on anti-M\u00fcllerian hormone levels","volume":"54","author":"Henes","year":"2015","journal-title":"Rheumatology (Oxford)"},{"key":"2020032810045921700_ref16","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1093\/humrep\/dew032","article-title":"Infertile women below the age of 40 have similar anti-M\u00fcllerian hormone levels and antral follicle count compared with women of the same age with no history of infertility","volume":"31","author":"Hvidman","year":"2016","journal-title":"Hum Reprod"},{"key":"2020032810045921700_ref17","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.1093\/humrep\/dev230","article-title":"Outcomes of transplantations of cryopreserved ovarian tissue to 41 women in Denmark","volume":"30","author":"Jensen","year":"2015","journal-title":"Hum Reprod"},{"key":"2020032810045921700_ref18","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1093\/molehr\/gat024","article-title":"Which follicles make the most anti-Mullerian hormone in humans? Evidence for an abrupt decline in AMH production at the time of follicle selection","volume":"19","author":"Jeppesen","year":"2013","journal-title":"Mol Hum Reprod"},{"key":"2020032810045921700_ref19","doi-asserted-by":"crossref","first-page":"e22024","DOI":"10.1371\/journal.pone.0022024","article-title":"A validated model of serum anti-m\u00fcllerian hormone from conception to menopause","volume":"6","author":"Kelsey","year":"2011","journal-title":"PLoS One"},{"key":"2020032810045921700_ref20","doi-asserted-by":"crossref","first-page":"e71465","DOI":"10.1371\/journal.pone.0071465","article-title":"Ovarian volume throughout life: a validated normative model","volume":"8","author":"Kelsey","year":"2013","journal-title":"PLoS One"},{"key":"2020032810045921700_ref21","first-page":"A175","article-title":"Development of a second generation anti-Mullerian hormone (AMH) ELISA","volume":"55","author":"Kumar","year":"2009","journal-title":"Clin Chem"},{"key":"2020032810045921700_ref22","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.fertnstert.2012.04.021","article-title":"Centers of FertiPROTEKT network. Reduced pretreatment ovarian reserve in premenopausal female patients with Hodgkin lymphoma or non-Hodgkin-lymphoma--evaluation by using antim\u00fcllerian hormone and retrieved oocytes","volume":"98","author":"Lawrenz","year":"2012","journal-title":"Fertil Steril"},{"key":"2020032810045921700_ref23","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1177\/0961203311409272","article-title":"Impact of systemic lupus erythematosus on ovarian reserve in premenopausal women: evaluation by using anti-Muellerian hormone","volume":"20","author":"Lawrenz","year":"2011","journal-title":"Lupus"},{"key":"2020032810045921700_ref24","doi-asserted-by":"crossref","first-page":"825","DOI":"10.3346\/jkms.2017.32.5.825","article-title":"Reference values for the revised anti-M\u00fcllerian hormone generation II assay: infertile population-based study","volume":"32","author":"Lee","year":"2017","journal-title":"J Korean Med Sci"},{"key":"2020032810045921700_ref25","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s10815-016-0689-1","article-title":"Female patients with lymphoma demonstrate diminished ovarian reserve even before initiation of chemotherapy when compared with healthy controls and patients with other malignancies","volume":"33","author":"Lekovich","year":"2016","journal-title":"J Assist Reprod Genet"},{"key":"2020032810045921700_ref26","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.rbmo.2019.01.006","article-title":"Overnight ovarian tissue transportation for centralized cryobanking \u2013 a feasible option","volume":"38","author":"Liebenthron","year":"2019","journal-title":"Reprod Biomed Online"},{"key":"2020032810045921700_ref27","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.fertnstert.2013.03.046","article-title":"The impact of culture conditions on early follicle recruitment and growth from human ovarian cortex biopsies in vitro","volume":"100","author":"Liebenthron","year":"2013","journal-title":"Fertil Steril"},{"key":"2020032810045921700_ref28","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.fertnstert.2014.12.114","article-title":"Comparison of antim\u00fcllerian hormone levels and antral follicle count as predictor of ovarian response to controlled ovarian stimulation in good-prognosis patients at individual fertility clinics in two multicenter trials","volume":"103","author":"Nelson","year":"2015","journal-title":"Fertil Steril"},{"key":"2020032810045921700_ref29","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1148\/radiology.153.1.6473771","article-title":"Pelvic organs in premenarcheal girls: real-time ultrasonography","volume":"153","author":"Orsini","year":"1984","journal-title":"Radiology"},{"key":"2020032810045921700_ref30","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3329\/bmrcb.v40i1.20323","article-title":"Cadaver study of the volume of the ovary in Bangladeshi women","volume":"40","author":"Perven","year":"2014","journal-title":"Bangladesh Med Res Counc Bull"},{"key":"2020032810045921700_ref31","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.fertnstert.2008.10.055","article-title":"True ovarian volume is underestimated by two-dimensional transvaginal ultrasound measurement","volume":"93","author":"Rosendahl","year":"2010","journal-title":"Fertil Steril"},{"key":"2020032810045921700_ref32","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.fertnstert.2018.10.018","article-title":"Serum antim\u00fcllerian hormone is associated with the number of oocytes matured in vitro and with primordial follicle density in candidates for fertility preservation","volume":"111","author":"Sermondade","year":"2019","journal-title":"Fertil Steril"},{"key":"2020032810045921700_ref33","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1093\/humrep\/dew165","article-title":"Ninety-five orthotopic transplantations in 74 women of ovarian tissue after cytotoxic treatment in a fertility preservation network: tissue activity, pregnancy and delivery rates","volume":"31","author":"van der Ven","year":"2016","journal-title":"Hum Reprod"},{"key":"2020032810045921700_ref34","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1093\/humrep\/det442","article-title":"Decreased serum anti-M\u00fcllerian hormone levels in girls with newly diagnosed cancer","volume":"29","author":"van Dorp","year":"2014","journal-title":"Hum Reprod"},{"key":"2020032810045921700_ref35","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s00404-017-4595-2","article-title":"Practical recommendations for fertility preservation in women by the FertiPROTEKT network. Part II: fertility preservation techniques","volume":"297","author":"von Wolff","year":"2018","journal-title":"Arch Gynecol Obstet"},{"key":"2020032810045921700_ref36","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1007\/s10815-018-1227-0","article-title":"Fertility preservation: ovarian response to freeze oocytes is not affected by different malignant diseases-an analysis of 992 stimulations","volume":"35","author":"von Wolff","year":"2018","journal-title":"J Assist Reprod Genet"},{"key":"2020032810045921700_ref37","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0008772","article-title":"Human ovarian reserve from conception to the menopause","volume":"5","author":"Wallace","year":"2010","journal-title":"PLoS One"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/humrep\/article-pdf\/34\/12\/2513\/32974613\/dez215.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/humrep\/article-pdf\/34\/12\/2513\/32974613\/dez215.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,3,28]],"date-time":"2020-03-28T14:05:31Z","timestamp":1585404331000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/article\/34\/12\/2513\/5643514"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,29]]},"references-count":37,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,11,29]]},"published-print":{"date-parts":[[2019,12,1]]}},"URL":"https:\/\/doi.org\/10.1093\/humrep\/dez215","relation":{},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,12]]},"published":{"date-parts":[[2019,11,29]]}}}