FERTILITY AND STERILITY
Vol. 55, No.6, June 1991
Printed on (l£id-free paper in U.S.A.
Copyright 1991 The American Fertility Society
Prolonged follicle stimulation decreases pregnancy rates after in vitro fertilization
Leon Clark, M.D. James Stanger, Ph.D.* Maxwell Brinsmead, M.D.t Lingard Fertility Centre and the University of Newcastle, Newcastle, New South Wales, Australia
The short-term application of gonadotropin-releasing hormone agonists (GnRH-a) is an alternative protocol to established methods of controlled ovarian hyperstimulation in in vitro fertilization (IVF) and gamete intrafallopian transfer. It is characterized by an initial gonadotropin secretion or "flare response" followed by pituitary down regulation and suppression of the lutenizing hormone (LH) surge. Although the advantages of this method include a short period of stimulation, less human menopausal gonadotropin (hMG) and increased flexibility in the duration of follicle stimulation, the optimal criteria for the timing of the administration of human chorionic gonadotropin (hCG), have yet to be established. 1 Generally, this has been based on the size of the leading follicle or follicles, with various criteria ranging from 15 mm to 20 mm. Because the duration of the follicular growth is not limited by a midcycle LH surge, the potential exists for manipulating the length of the follicular phase in ways not possible with most previous stimulation protocols, e.g., clomiphene citrate + hMG or hMG alone. The aim is to improve pregnancy rates (PRs) by optimizing the number of mature follicles at oocyte aspiration. If, however, the time when hCG is given is not critical, then a consequence of this may be a reduction in weekend or evening aspirations. This would both increase convenience and reduce the overall cost of the service. With both these goals in mind, it was Received June 1, 1990; revised and accepted February 21, 1991.
* Reprint requests: James Stanger, Ph.D., Lingard Fertility Centre, Merewether, Newcastle, New South Wales 2291, Australia. t Department of Reproductive Medicine, Faculty of Medicine, University of Newcastle. 1192
Clark et aI.
Communications-in-brief
decided to explore the impact of 1 additional day of follicle growth beyond our normal criteria before inducing ovulation with hCG. MATERIALS AND METHODS
Follicle stimulation was initiated with 0.5 to 1 mgjd subcutaneous injections of leuprolide acetate (LA, Lucrin; Abbott Australasia, Sydney, Australia), starting between day 2 and day 5, depending on cycle length, and continuing until the day of hCG. Human menopausal gonadotropin (Pergonal; Serono, Aubonne, Switzerland or Humagon; Organon, Oss, The Netherlands) was administered at the rate of between 75 and 325 IUjd by intramuscular injection from the 2nd day of LA until the morning of hCG (Profasi; Serono). Baseline estradiol (E2), progesterone, and LH concentrations (Amerlite; Amersham International, Amersham, United Kingdom) were measured on the 1st day of LA. Estradiol was again measured on day 4 and daily from the 8th day of LA. On the basis of our previous experience with this protocol, cycles were canceled if the serum E2 was 380 pgjmL on day 4 of treatment. Human chorionic gonadotropin was administered when two or more follicles had a diameter of 17 mm or greater. Ovum pick-up was performed 36 hours after hCG, and embryo transfer of usually three, but in some cases four, embryos was performed 44 to 48 hours later.2 Transferred embryos were graded as either A, B, or C depending on uniformity and color of blastomeres and the presence and extent of fragmentation. Luteal support of 2,000 IU hCG was given 1M on days 2, 5, and 8 after ovum recovery. Fertility and Sterility
Table 1
Type of Infertility and Ovarian Response to Standard (A) and Prolonged (B) Follicle Recruitment
No. of patients No. of tubal infertility Age (y) Ampules of hMG Duration of stimulation (d) Sperm concentration (X106 /mL) Maximum E2 at hCG (pg/mL) No. of follicles
Vol. 55, No.6, June 1991
Printed on (l£id-free paper in U.S.A.
Copyright 1991 The American Fertility Society
Prolonged follicle stimulation decreases pregnancy rates after in vitro fertilization
Leon Clark, M.D. James Stanger, Ph.D.* Maxwell Brinsmead, M.D.t Lingard Fertility Centre and the University of Newcastle, Newcastle, New South Wales, Australia
The short-term application of gonadotropin-releasing hormone agonists (GnRH-a) is an alternative protocol to established methods of controlled ovarian hyperstimulation in in vitro fertilization (IVF) and gamete intrafallopian transfer. It is characterized by an initial gonadotropin secretion or "flare response" followed by pituitary down regulation and suppression of the lutenizing hormone (LH) surge. Although the advantages of this method include a short period of stimulation, less human menopausal gonadotropin (hMG) and increased flexibility in the duration of follicle stimulation, the optimal criteria for the timing of the administration of human chorionic gonadotropin (hCG), have yet to be established. 1 Generally, this has been based on the size of the leading follicle or follicles, with various criteria ranging from 15 mm to 20 mm. Because the duration of the follicular growth is not limited by a midcycle LH surge, the potential exists for manipulating the length of the follicular phase in ways not possible with most previous stimulation protocols, e.g., clomiphene citrate + hMG or hMG alone. The aim is to improve pregnancy rates (PRs) by optimizing the number of mature follicles at oocyte aspiration. If, however, the time when hCG is given is not critical, then a consequence of this may be a reduction in weekend or evening aspirations. This would both increase convenience and reduce the overall cost of the service. With both these goals in mind, it was Received June 1, 1990; revised and accepted February 21, 1991.
* Reprint requests: James Stanger, Ph.D., Lingard Fertility Centre, Merewether, Newcastle, New South Wales 2291, Australia. t Department of Reproductive Medicine, Faculty of Medicine, University of Newcastle. 1192
Clark et aI.
Communications-in-brief
decided to explore the impact of 1 additional day of follicle growth beyond our normal criteria before inducing ovulation with hCG. MATERIALS AND METHODS
Follicle stimulation was initiated with 0.5 to 1 mgjd subcutaneous injections of leuprolide acetate (LA, Lucrin; Abbott Australasia, Sydney, Australia), starting between day 2 and day 5, depending on cycle length, and continuing until the day of hCG. Human menopausal gonadotropin (Pergonal; Serono, Aubonne, Switzerland or Humagon; Organon, Oss, The Netherlands) was administered at the rate of between 75 and 325 IUjd by intramuscular injection from the 2nd day of LA until the morning of hCG (Profasi; Serono). Baseline estradiol (E2), progesterone, and LH concentrations (Amerlite; Amersham International, Amersham, United Kingdom) were measured on the 1st day of LA. Estradiol was again measured on day 4 and daily from the 8th day of LA. On the basis of our previous experience with this protocol, cycles were canceled if the serum E2 was 380 pgjmL on day 4 of treatment. Human chorionic gonadotropin was administered when two or more follicles had a diameter of 17 mm or greater. Ovum pick-up was performed 36 hours after hCG, and embryo transfer of usually three, but in some cases four, embryos was performed 44 to 48 hours later.2 Transferred embryos were graded as either A, B, or C depending on uniformity and color of blastomeres and the presence and extent of fragmentation. Luteal support of 2,000 IU hCG was given 1M on days 2, 5, and 8 after ovum recovery. Fertility and Sterility
Table 1
Type of Infertility and Ovarian Response to Standard (A) and Prolonged (B) Follicle Recruitment
No. of patients No. of tubal infertility Age (y) Ampules of hMG Duration of stimulation (d) Sperm concentration (X106 /mL) Maximum E2 at hCG (pg/mL) No. of follicles
