Assisted reproductive technology! FERTILITY AND STERILITY Copyright
©
Vol. 58, No.6, December 1992
1992 The American Fertility Society
Printed on acid-free paper in U.S.A.
Ultrashort gonadotropin-releasing hormone agonist (GnRH-a) protocol in comparison with the long-acting GnRH-a protocol and menotropin alone
Raphael Ron-El, M.D.' Arie Herman, M.D. Abraham Golan, M.D.
Yigal Soffer, M.D. Hanna Nachum, Technician Eliahu Caspi, M.D.
Department of Obstetrics and Gynecology, Assaf Harofeh Medical Center, Affiliated With the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Objective: To compare the in vitro fertilization and embryo transfer (lVF-ET) outcome of a 3day gonadotropin-releasing hormone agonist (GnRH-a) administration: ultrashort protocol with the outcome of long-acting GnRH-a cycles or human menopausal gonadotropin (hMG) alone. Design: Ninety-two cycles of the ultrashort protocol were matched with 92 cycles with long GnRH-a and with 92 hMG cycles. Setting: The IVF -ET program. Main Outcome Measures: Amount and duration of hMG treatment, hormonal profile on the day of human chorionic gonadotropin administration, cancellation rate, number of oocytes retrieved, and fertilization and pregnancy rates (PRs) were examined and compared among the three groups. Results: The ultrashort group needed a higher number of hMG ampules than the hMG group but significantly less than in the long GnRH-a regimen. The number of oocytes in the ultrashort protocol was the same as in the long GnRH-a, but the number of embryos per retrieval was significantly lower than with the long GnRH-a protocol and similar to that found in the hMG group. The ultrashort protocol yielded 10% PR per cycle and 17% per replacement, significantly lower than with the long GnRH-a protocol, 26% and 36%, respectively, but also lower than in the hMG one, namely 13% and 28%. Conclusion: The ultrashort protocol, although being convenient and having some advantages found in the long GnRH -a protocol, is inferior in its outcome compared with the two other protocols. Fertil Steril 1992;58:1164-8 Key Words: Gonadotropin-releasing hormone agonist, induction of ovulation, in vitro fertilization and embryo transfer
The use of gonadotropin-releasing hormone agonist (GnRH-a) before ovarian hyperstimulation for in vitro fertilization and embryo transfer (IVF -ET) treatment has some advantages that have already been reported. Among them are the following: increased number of follicles in poor (1) and normal responders (2, 3); decreased production of ovarian
Received February 4, 1992; revised and accepted July 29, 1992. * Reprint requests: Raphael Ron-El, M.D., Department ofOb-
stetrics and Gynecology, Assaf Harofeh Medical Center, Zerifin 70300, IsraeL 1164
Ron-EI et al.
Ultrashort GnRH-a protocol
androgens (4); significant decrease of late follicular phase luteinizing hormone (LH) levels (3, 5); and a significant lower cancellation rate (2,3). Long-term use of GnRH -a has the disadvantages of achieving complete pituitary desensitization (estradiol [E21 :::S; 30 pg/mL) only after 18 days in 90% of the patients (6) and requires significantly larger doses of exogenous gonadotropins for adequate follicular development (3, 6). Recently, Macnamee et al. (7) has shown that 3day administration of GnRH -a in the early follicular phase induced a suppression of gonadotropin secretion in the late follicular phase. The addition of huFertility and Sterility
man menopausal gonadotropin (hMG) yielded a significantly low cancellation rate and a significantly higher pregnancy rate (PR) per replacement in comparison with the clomiphene citrate and hMG protocol. Human menopausal gonadotropin is given in the ultrashort protocol exactly in the same manner as in the short one. The long protocol includes the phase in which pituitary desensitization is achieved after the administration of a depot long-acting GnRH-a or a short-acting GnRH-a given on the same basis. Only when suppression is achieved (E 2 level::; 30 pgjmL), hMG treatment begins contemporaneously with the GnRH-a suppressive effect up to the human chorionic gonadotropin (hCG) day. In the previous study, we demonstrated the superiority of outcome of IVF -ET cycles with the long GnRH -a over the hMG protocol. The purpose of the current study was to compare the results of ovarian response and IVF-ET outcome in a 3-day GnRH-a protocol with a long-acting GnRH-a scheme and hMG alone regimen. MATERIALS AND METHODS
The short protocol that was previously described (8) consists of a daily administration of a short-acting GnRH-a from cycle day 2 up to the last day of hMG administration. Human menopausal gonadotropin is commenced on cycle day 3, three ampules per day for 3 days and then individually adjusted up to the appearance of a leading follicle ~ 18-mm diameter on the ultrasound scan. The short scheme in the present study was named ultrashort protocol to differentiate it from the short protocol. In this ultrashort protocol, a short-acting GnRH -a is given for only 3 days, on cycle days 2, 3, and 4. Patients who were able to attend the clinic on the 1st or 2nd day oftheir menstrual cycle were allocated to the ultrashort protocol and created the study group. The cycles were match controlled with cycles in our two other contemporaneous protocols, namely long-acting GnRH-a combined with hMG and hMG alone. The patients were matched by age and indication for IVF. Blood sample taken on the 2nd cycle day was assayed for progesterone (P), and the ovaries were scanned for the presence of cysts> 15 mm of diameter. IfP level was
©
Vol. 58, No.6, December 1992
1992 The American Fertility Society
Printed on acid-free paper in U.S.A.
Ultrashort gonadotropin-releasing hormone agonist (GnRH-a) protocol in comparison with the long-acting GnRH-a protocol and menotropin alone
Raphael Ron-El, M.D.' Arie Herman, M.D. Abraham Golan, M.D.
Yigal Soffer, M.D. Hanna Nachum, Technician Eliahu Caspi, M.D.
Department of Obstetrics and Gynecology, Assaf Harofeh Medical Center, Affiliated With the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Objective: To compare the in vitro fertilization and embryo transfer (lVF-ET) outcome of a 3day gonadotropin-releasing hormone agonist (GnRH-a) administration: ultrashort protocol with the outcome of long-acting GnRH-a cycles or human menopausal gonadotropin (hMG) alone. Design: Ninety-two cycles of the ultrashort protocol were matched with 92 cycles with long GnRH-a and with 92 hMG cycles. Setting: The IVF -ET program. Main Outcome Measures: Amount and duration of hMG treatment, hormonal profile on the day of human chorionic gonadotropin administration, cancellation rate, number of oocytes retrieved, and fertilization and pregnancy rates (PRs) were examined and compared among the three groups. Results: The ultrashort group needed a higher number of hMG ampules than the hMG group but significantly less than in the long GnRH-a regimen. The number of oocytes in the ultrashort protocol was the same as in the long GnRH-a, but the number of embryos per retrieval was significantly lower than with the long GnRH-a protocol and similar to that found in the hMG group. The ultrashort protocol yielded 10% PR per cycle and 17% per replacement, significantly lower than with the long GnRH-a protocol, 26% and 36%, respectively, but also lower than in the hMG one, namely 13% and 28%. Conclusion: The ultrashort protocol, although being convenient and having some advantages found in the long GnRH -a protocol, is inferior in its outcome compared with the two other protocols. Fertil Steril 1992;58:1164-8 Key Words: Gonadotropin-releasing hormone agonist, induction of ovulation, in vitro fertilization and embryo transfer
The use of gonadotropin-releasing hormone agonist (GnRH-a) before ovarian hyperstimulation for in vitro fertilization and embryo transfer (IVF -ET) treatment has some advantages that have already been reported. Among them are the following: increased number of follicles in poor (1) and normal responders (2, 3); decreased production of ovarian
Received February 4, 1992; revised and accepted July 29, 1992. * Reprint requests: Raphael Ron-El, M.D., Department ofOb-
stetrics and Gynecology, Assaf Harofeh Medical Center, Zerifin 70300, IsraeL 1164
Ron-EI et al.
Ultrashort GnRH-a protocol
androgens (4); significant decrease of late follicular phase luteinizing hormone (LH) levels (3, 5); and a significant lower cancellation rate (2,3). Long-term use of GnRH -a has the disadvantages of achieving complete pituitary desensitization (estradiol [E21 :::S; 30 pg/mL) only after 18 days in 90% of the patients (6) and requires significantly larger doses of exogenous gonadotropins for adequate follicular development (3, 6). Recently, Macnamee et al. (7) has shown that 3day administration of GnRH -a in the early follicular phase induced a suppression of gonadotropin secretion in the late follicular phase. The addition of huFertility and Sterility
man menopausal gonadotropin (hMG) yielded a significantly low cancellation rate and a significantly higher pregnancy rate (PR) per replacement in comparison with the clomiphene citrate and hMG protocol. Human menopausal gonadotropin is given in the ultrashort protocol exactly in the same manner as in the short one. The long protocol includes the phase in which pituitary desensitization is achieved after the administration of a depot long-acting GnRH-a or a short-acting GnRH-a given on the same basis. Only when suppression is achieved (E 2 level::; 30 pgjmL), hMG treatment begins contemporaneously with the GnRH-a suppressive effect up to the human chorionic gonadotropin (hCG) day. In the previous study, we demonstrated the superiority of outcome of IVF -ET cycles with the long GnRH -a over the hMG protocol. The purpose of the current study was to compare the results of ovarian response and IVF-ET outcome in a 3-day GnRH-a protocol with a long-acting GnRH-a scheme and hMG alone regimen. MATERIALS AND METHODS
The short protocol that was previously described (8) consists of a daily administration of a short-acting GnRH-a from cycle day 2 up to the last day of hMG administration. Human menopausal gonadotropin is commenced on cycle day 3, three ampules per day for 3 days and then individually adjusted up to the appearance of a leading follicle ~ 18-mm diameter on the ultrasound scan. The short scheme in the present study was named ultrashort protocol to differentiate it from the short protocol. In this ultrashort protocol, a short-acting GnRH -a is given for only 3 days, on cycle days 2, 3, and 4. Patients who were able to attend the clinic on the 1st or 2nd day oftheir menstrual cycle were allocated to the ultrashort protocol and created the study group. The cycles were match controlled with cycles in our two other contemporaneous protocols, namely long-acting GnRH-a combined with hMG and hMG alone. The patients were matched by age and indication for IVF. Blood sample taken on the 2nd cycle day was assayed for progesterone (P), and the ovaries were scanned for the presence of cysts> 15 mm of diameter. IfP level was
