Reply of the Authors: Is “restoration of ovarian function or ovarian reserve” possible after ovarian surgery?

LETTER TO THE EDITOR Reply of the Authors: We would like to thank Professor Sonmezer et al. for their interest in our work (1). Our study investigated the serial changes of serum anti-M€ ullerian 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. Ovarian reserve is defined as the functional potential of the ovary and reflects the number and quality of the follicles left in the ovary at any given time (2). However, there are currently no definite estimates to measure quantitative ovarian reserve in reproductive age. Instead, various tests and markers reflecting ovarian reserve have been developed, such as ovarian responses to hyperstimulation (3) or other hormonal tests such as FSH, inhibin B, E2, and AMH levels on day 3 of the menstrual cycle (4). Among these factors, serum AMH levels have recently been acknowledged to reflect ovarian reserve along with the serum FSH and E2 levels studied on day 3 of the menstrual cycle. The use of a cycle-independent serum marker to predict the ovarian reserve is thought to be more attractive than the time-consuming and not always well standardized ovarian reserve tests used in earlier studies (5).

malian ovary that are capable of replenishing the pool of follicles (6). ‘‘Acute ovarian failure’’ refers to the loss of ovarian function that arises during or shortly after the completion of cancer therapy. By contrast, ‘‘premature menopause’’ refers to the loss of ovarian function that occurs years after completion of cancer therapy after a window of normal functioning. Many prepubertal and adolescent female cancer survivors demonstrate normalization of FSH levels over time, and only a minority appears to experience irreversible ovarian failure requiring long-term hormone therapy (7). Although histological examinations of ovarian tissue and ultrasound findings of these women have revealed a decreased number of ovarian follicles and follicular growth compared with age-matched controls, they recovered ovarian function, experienced regular menstruation, and even conceived naturally (8). This means that part of the ovarian function has undergone a reversible change during or after cancer therapy. Because the mechanism of serum AMH improvement after ovarian cystectomy has not been elucidated, ‘‘restoration of ovarian reserve’’ is not definitely incorrect. We are confident that our conclusion should remain as it is. Our study suggests that we should measure serum AMH levels to assess ovarian reserve function more exactly at least 3 months after ovarian cystectomy.

We assessed ovarian reserve by measuring the serum AMH level. The change in AMH level indirectly reflects the change in ovarian reserve. Of course, vascular damage during ovarian surgery could induce the initial decrease of the serum AMH level.

Hye Jin Chang, M.D., Ph.D. Department of Obstetrics and Gynecology, and Health Promotion Center Seoul, South Korea

We suggested several possible mechanisms of recovery in ovarian reserve, as reflected by AMH level, after the initial decrease from ovarian cystectomy. The improvement in serum AMH levels may reflect a reperfusion of ovarian tissue, compensatory reactive hyperfunctioning of granulosa cells, rescue from atretic follicles, and, the most controversial theory, regeneration of ovarian follicles. There may be proliferating germ cells present in the postnatal mam-

Chang Suk Suh, M.D., Ph.D. Department of Obstetrics and Gynecology Seoul National University Bundang Hospital Seoul, South Korea February 16, 2010 doi:10.1016/j.fertnstert.2010.02.034

REFERENCES 1. Chang HJ, Han SH, Lee JR, Jee BC, Lee BI, Suh CS, et al. Impact of laparoscopic cystectomy on ovarian reserve: serial changes of serum anti-Mullerian hormone levels. Fertil Steril 2009. doi: 10.1016/j.fertnstert.2009.02.022. 2. Block E. Quantitative morphological investigations of the follicular system in women; variations at different ages. Acta Anat (Basel) 1952;14:108–23. 3. Maheshwari A, Fowler P, Bhattacharya S. Assessment of ovarian reserve—should we perform tests of ovarian reserve routinely? Hum Reprod 2006;21:2729–35.

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4. Fanchin R, Schonauer LM, Righini C, Guibourdenche J, Frydman R, Taieb J. Serum anti-Mullerian hormone is more strongly related to ovarian follicular status than serum inhibin B, estradiol, FSH and LH on day 3. Hum Reprod 2003;18: 323–7. 5. Hehenkamp WJ, Looman CW, Themmen AP, de Jong FH, Te Velde ER, Broekmans FJ. Anti-Mullerian hormone levels in the spontaneous menstrual cycle do not show substantial fluctuation. J Clin Endocrinol Metab 2006;91:4057–63.

6. Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 2004;428:145–50. 7. Sklar C. Maintenance of ovarian function and risk of premature menopause related to cancer treatment. J Natl Cancer Inst Monogr 2005;25–7. 8. Larsen EC, Muller J, Schmiegelow K, Rechnitzer C, Andersen AN. Reduced ovarian function in long-term survivors of radiation- and chemotherapy-treated childhood cancer. J Clin Endocrinol Metab 2003;88: 5307–14.

Fertility and Sterility Vol. 93, No. 7, May 1, 2010 Copyright ª2010 American Society for Reproductive Medicine, Published by Elsevier Inc.

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