FERTILITY AND STERILITY威 VOL. 78, NO. 1, JULY 2002 Copyright ©2002 American Society for Reproductive Medicine Published by Elsevier Science Inc. Printed on acid-free paper in U.S.A.
Ovarian reserve after uterine artery embolization for leiomyomata One of the newest treatments of uterine leiomyomata is uterine artery embolization. However, several women have become menopausal after this procedure (1–3). It seems that premature menopause after embolization occurs predominantly in older women. Whether uterine artery embolization decreases ovarian function in younger women is unknown. We sought to evaluate ovarian reserve and ovarian stromal blood flow before and after uterine artery embolization. From January 2000 to June 2001, 48 premenopausal women with symptomatic uterine myomata underwent bilateral uterine artery embolization. Twenty-three of these women had baseline serum FSH levels ⬍ 10 mIU/mL. Uterine artery embolization was performed bilaterally in all cases by using 350- to 500-m polyvinyl alcohol particles (Boston Scientific, Target Therapeutics Division, Fremont, CA). Before uterine artery embolization, samples of blood were drawn for FSH and E2 measurement. The volume of the myomata, ovarian volume, antral follicle count, and ovarian stromal blood flow were measured. All scans were performed by one investigator (TJC) by using a 5-MHz transvaginal transducer with color and pulsed Doppler facilities. All of these tests were done on day 3 of the menstrual cycle before embolization and in the first and third cycle after embolization. The Research and Ethics Board of the Royal Victoria Hospital approved the study. Data were analyzed by using the Student t-test and Mann–Whitney test. Two-tailed P⬍.05 was considered statistically significant. The mean age of the participants was 44.1⫾2.4 years. The volume of the largest myoma was 196.4⫾36.6 cm3 before embolization, 129.7⫾25.3 cm3 1 month after embolization, and 91.3⫾18.4 cm3 3 months after embolization, respectively. The diameter of the largest myoma had decreased significantly 3 months after embolization (P⬍.01). Serum FSH levels gradually increased over time (Table 1). A level ⬎10 mIU/mL was found in seven women 1 month after uterine artery embolization and in 9 women 3 months after the procedure. The highest levels were 22.8 mIU/mL and 33.8 mIU/mL at 1 month and 3 months after the procedure, respectively. No significant difference in E2 levels, ovarian volume, number of antral follicles, and ovarian stromal blood flows before, 1 month after, and 3 months after uterine artery embolization was observed. Day 3 serum FSH level is an indirect measure of ovarian reserve (4). In agreement with a previous observation (5), basal FSH levels increased after uterine artery embolization. We also found a trend toward increasing serum E2 levels. These changes suggest a decreasing ovarian reserve. The high E2 levels indicate accelerated follicular recruitment in response to elevated FSH secretion. The declining ovarian reserve is also indicated by the decreasing number of antral follicles. Received October 16, 2001; revised and accepted December 28, 2001. Reprint requests: Togas Tulandi, M.D., Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec H3A 1A1, Canada (FAX: 514-843-1448; E-mail: [email protected]
muhc.mcgill.ca). 0015-0282/02/$22.00 PII S0015-0282(02)03164-3
The most likely mechanism of declining ovarian reserve and premature menopause after uterine artery embolization is embolization of the utero-ovarian collateral circulation. This effect compromises blood supply to the ovaries. We could not demonstrate changes in the ovarian stromal blood flow after uterine artery embolization. Perhaps these changes were subtle and could not be detected by ultrasonography. Transient ovarian failure after uterine artery embolization has been described. Uterine artery embolization may hasten ovarian failure. In our series, the FSH levels 3 months after embolization were higher than the levels at 1 month after uterine artery embolization and the baseline levels in all patients. Whether ovarian function will return to normal 6 or 12 months after embolization is unknown. However, in agreement with others (1–3), we found permanent ovarian failure with severe menopausal symptoms in a 40-year-old woman immediately after uterine artery embolization (unpublished data). Ravina et al. (6) reported 12 pregnancies after uterine artery embolization. Of these, 5 resulted in miscarriage and 3 in preterm deliveries. This high rate of miscarriage is of concern. Although it has not been reported, the decrease in uterine blood flow after uterine artery embolization can also lead to intrauterine
TABLE 1 Serum FSH and estradiol levels, number of antral follicles, ovarian volume, and stromal blood flows before, 1 month after, and 3 months after uterine artery embolization. Characteristic FSH level (mIU/mL) E2 level (pmol/L) No. of antral follicles Right Left Ovarian volume (cm3) Right Left Pulsatility index of ovarian arteries Right Left Vmax (cm/s) Right Left
1 month after UAE
3 months after UAE
5.7 ⫾ 0.5 199.1 ⫾ 38.4
9.0 ⫾ 1.1a 204.8 ⫾ 41.7
10.7 ⫾ 2.3b 253.6 ⫾ 60.5
3.5 ⫾ 0.4 2.5 ⫾ 0.4
2.6 ⫾ 0.3 1.9 ⫾ 0.4
2.1 ⫾ 0.6 1.5 ⫾ 0.3
5.5 ⫾ 0.8 4.5 ⫾ 0.7
4.7 ⫾ 0.8 4.6 ⫾ 0.9
5.3 ⫾ 0.7 4.7 ⫾ 0.8
0.7 ⫾ 0.1 0.7 ⫾ 0.2
0.7 ⫾ 0.1 0.6 ⫾ 0.1
0.7 ⫾ 0.1 0.6 ⫾ 0.1
8.1 ⫾ 1.6 5.9 ⫾ 1.5
7.2 ⫾ 1.5 6.3 ⫾ 1.4
7.3 ⫾ 1.7 7.5 ⫾ 2.2
Note: UAE ⫽ uterine artery embolization. P⬍0.01 vs. before embolization. b P⬍0.05 vs. before embolization. a
Tulandi. Ovarian reserve after uterine artery embolization. Fertil Steril 2002.
growth restriction. To date, reports of pregnancy after uterine artery embolization are anecdotal and descriptions of live birth are still limited.
Tulandi et al.
Our results suggest that uterine artery embolization decreases ovarian reserve. Because of concern about loss of ovarian function and risks of premature menopause, this procedure should be reserved for women who do not desire future fertility. Togas Tulandi, M.D.a Aref Sammour, M.D.a David Valenti M.D.b Timothy J. Child, M.D.a Laurent Seti, M.D.a Seang Lin Tan, M.D.a Department of Obstetrics and Gynecology,a and Department of Radiology,b McGill University, Montreal, Quebec, Canada
References 1. Hurst BS, Stackhouse DJ, Matthews M, Marshburn PB. Uterine artery embolization for symptomatic uterine myomas. Fertil Steril 2000;74: 855– 69. 2. Chrisman HB, Saker M, Ryu R, Nemcek AA Jr, Gerbie MV, Milad MP, et al. The impact of uterine fibroid embolization on resumption of menses and ovarian function. J Vasc Interv Radiol 2000;11:699 –703. 3. Stringer NH, Grant T, Park J, Oldham J. Ovarian failure after uterine artery embolization for treatment of myomas. J Am Assoc Gynecol Laparosc 2000;7:395– 400. 4. Scott RT, Toner JP, Muasher SJ, Oehninger S, Robinson S, Rosenwaks Z. Follicle stimulating hormone levels on day 3 are predictive of in vitro fertilization outcome. Fertil Steril 1989;51:651– 4. 5. Spies JB, Roth AR, Gonsalves SM, Murphy-Skrzyniarz. Ovarian function after uterine artery embolization for leiomyomata: assessment with use of serum follicle stimulating hormone. J Vasc Interv Radiol 2001; 12:437– 42. 6. Ravina JH, Cigaru-Vigneron N, Aymard A, Le Dref O, Merland JJ. Pregnancy after embolization of uterine myoma: report of 12 cases. Fertil Steril 2000;73:1241–3.
Vol. 78, No. 1, July 2002