Is “restoration of ovarian function or ovarian reserve” possible after ovarian surgery?

Abstract

To the Editor: We read the prospective study by Chang et al. (1Chang H.J. Han S.H. Lee J.R. Jee B.C. Lee B.I. Suh C.S. et al.Impact of laparoscopic cystectomy on ovarian reserve: serial changes of serum anti-Müllerian hormone levels.Fertil Steril. 2009; (doi: 10.1016/j.fertnstert.2009.02.022)Google Scholar) regarding the effect of ovarian surgery on ovarian reserve with great interest. The authors reported the impact of laparoscopic cystectomy on ovarian reserve in 20 ovarian cysts including endometrioma, mature teratoma, and mucinous cystadenoma. There is no doubt that any surgical procedure involving ovaries may compromise ovarian reserve. The findings of the study regarding the endometriomas are especially important since there has been a continuing debate on whether endometriomas should be excised in infertile patients before assisted reproductive technologies (ART) or left in place owing to the surgery-related damage to ovarian reserve. Current studies showed that anti-Müllerian hormone (AMH), which is expressed in granulosa cells, is a promising marker of ovarian reserve (2Baarends W.M. Uilenbroek J.T. Kramer P. Hoogerbrugge J.W. van Leeuwen E.C. Themmen A.P. et al.Anti-Mullerian hormone and anti-Mullerian hormone type II receptor messenger ribonucleic acid expression in rat ovaries during postnatal development, the estrous cycle, and gonadotropin-induced follicle growth.Endocrinology. 1995; 136: 4951-4962Crossref PubMed Google Scholar, 3Weenen C. Laven J.S. Von Bergh A.R. Cranfield M. Groome N.P. Visser J.A. et al.Anti-Mullerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment.Mol Hum Reprod. 2004; 10: 77-83Crossref PubMed Scopus (979) Google Scholar). The AMH expression is initiated in the smallest growing follicles and declines in the early antral stages as one follicle is selected for dominance while remaining growing follicles become atretic (4Sahambi S.K. Visser J.A. Themmen A.P. Mayer L.P. Devine P.J. Correlation of serum anti-Müllerian hormone with accelerated follicle loss following 4-vinylcyclohexene diepoxide-induced follicle loss in mice.Reprod Toxicol. 2008; 26: 116-122Crossref PubMed Scopus (33) Google Scholar). Previous studies demonstrated that AMH is a more reliable marker for chemotherapy-associated ovarian damage, which shows more rapid change after chemotherapy compared with serum FSH or inhibin B (5Oktay K. Oktem O. Reh A. Vahdat L. Measuring the impact of chemotherapy on fertility in women with breast cancer.J Clin Oncol. 2006; 24: 4044-4046Crossref PubMed Scopus (67) Google Scholar). Furthermore, as opposed to sustained postchemotherapy serum levels of AMH, Anderson et al. (6Anderson R.A. Themmen A.P. Al-Qahtani A. Groome N.P. Cameron D.A. The effects of chemotherapy and long-term gonadotrophin suppression on the ovarian reserve in premenopausal women with breast cancer.Hum Reprod. 2006; 21: 2583-2592Crossref PubMed Scopus (284) Google Scholar) demonstrated that serum levels of FSH and inhibin B may recover in time, leading to a “misinterpretation” as ovarian reserve is recovered (6Anderson R.A. Themmen A.P. Al-Qahtani A. Groome N.P. Cameron D.A. The effects of chemotherapy and long-term gonadotrophin suppression on the ovarian reserve in premenopausal women with breast cancer.Hum Reprod. 2006; 21: 2583-2592Crossref PubMed Scopus (284) Google Scholar). Notably, when chemotherapy is given in extremely high doses, that is, in patients undergoing hematopoietic stem cell transplantation, premature ovarian failure is almost inevitable and no recovery is possible, with only a handful of primordial or growing follicles surviving. In the light of the findings of the clinical study by Chang et al. (1Chang H.J. Han S.H. Lee J.R. Jee B.C. Lee B.I. Suh C.S. et al.Impact of laparoscopic cystectomy on ovarian reserve: serial changes of serum anti-Müllerian hormone levels.Fertil Steril. 2009; (doi: 10.1016/j.fertnstert.2009.02.022)Google Scholar), as was discussed by the authors it is likely that AMH secretion is decreased as a result of both direct mechanical damage and electroinjury to the growing follicles. In theory, it is possible that among the follicle stockpile, actively growing follicles are most likely to be damaged by electrocoagulation or mechanical dissection compared with nondividing quiescent primordial follicles. The possible compromise in ovarian microvasculature may have a further detrimental effect on the growing follicles and the granulosa cells that primarily secrete AMH. Moreover, it is not clear whether the temperature increase in the “healthy” ovarian portions that ensues after electrocoagulation has a negative effect on all growing follicles in the coagulated ovary (7Mertyna P. Dewhirst M.W. Halpern E. Goldberg W. Goldberg S.N. Radiofrequency ablation: the effect of distance and baseline temperature on thermal dose required for coagulation.Hyperthermia. 2008; 24: 550-559Crossref PubMed Scopus (44) Google Scholar). The classical dogma regarding the fate of primordial follicles indicates that ovarian reserve diminishes inexorably throughout a woman's life and occurs in any physiological condition. Ovarian transplantation studies have clarified that the time required for a primordial follicle to reach preantral stages is about 120 days from its quiescence (8Bedaiwy M. El-Nashar S. El Saman A. Evers J. Sandadi S. Desai N. et al.Reproductive outcome after transplantation of ovarian tissue: a systematic review.Hum Reprod Update. 2008; 23: 2709-2717Crossref Scopus (68) Google Scholar). The increasing AMH secretion from the newly growing preantral follicles (4Sahambi S.K. Visser J.A. Themmen A.P. Mayer L.P. Devine P.J. Correlation of serum anti-Müllerian hormone with accelerated follicle loss following 4-vinylcyclohexene diepoxide-induced follicle loss in mice.Reprod Toxicol. 2008; 26: 116-122Crossref PubMed Scopus (33) Google Scholar), and its contribution to the “seemingly laboratory recovery of ovarian reserve” in about 90 days, is the main possible explanation of the findings of the study. When analyzing the findings of the current study, “restoration of ovarian function” or “restoration of decreased ovarian reserve” may not be a correct definition since it implies “formation of new ovarian follicles.” The hypothetical role of germ cell renewal to clarify this controversy can only be a speculation, rather than an established scientific fact, on the grounds of the current knowledge in humans. A possible role of bone morphogenetic protein to induce AMH gene expression may elucidate the primary role of AMH in follicular transition (9Shi J. Yoshino O. Osuga Y. Koga K. Hirota Y. Hirata T. et al.Bone morphogenetic protein-6 stimulates gene expression of follicle-stimulating hormone receptor, inhibin/activin beta subunits, and anti-Müllerian hormone in human granulosa cells.Fertil Steril. 2009; 92: 1794-1798Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar). Impact of laparoscopic cystectomy on ovarian reserve: serial changes of serum anti-Müllerian hormone levelsFertility and SterilityVol. 94Issue 1PreviewTo evaluate the ovarian reserve changes after laparoscopic cystectomy, we prospectively evaluated pre- and postoperative serum anti-Müllerian hormone (AMH) level, and ovarian volumes. Full-Text PDF Reply of the Authors: Is “restoration of ovarian function or ovarian reserve” possible after ovarian surgery?Fertility and SterilityVol. 93Issue 7PreviewWe would like to thank Professor Sonmezer et al. for their interest in our work (1). Our study investigated the serial changes of serum anti-Müllerian hormone (AMH) levels after laparoscopic ovarian cystectomy. The results showed that serum AMH levels significantly decreased on the seventh day postoperatively compared with the preoperative level. These findings supported that surgery-related ovarian damage could happen. The decreased serum AMH levels after surgery recovered to 65% of preoperative levels after 3 months. Full-Text PDF