Acta Obstet Gynecol Scand 1990; 69: 333-337
OVARIAN HYPERSTIMULATION FOR IN VITRO FERTILIZATION PRECEDED BY PROLONGED ADMINISTRATION OF A GONADOTROPIN-RELEASING HORMONE AGONIST Tom Tanbo, Per Olav Dale and Thomas Abyholm From the Department of Obstetrics and Gynecology, the National Hospital, University of Oslo, Oslo, Norway
Abstract. In 51 patients, controlled ovarian hyperstimulation with clomiphene citrate (CC)/human menopausal gonadotropin (hMG), or hMG only, in 702 IVF cycles had previously resulted in a cancellation rate of 52% and no pregnancies. In 54 subsequent cycles the women were treated with prolonged administration of a gonadotropin-releasing hormone agonist (GnRHa) followed by hMG stimulation, the GnRHa group. The results were compared with the outcome of 47 cycles in patients who came for their first IVF attempt. In this group a CClhMG regimen was used, the CClhMG group. In the GnRHa group, 17 pregnancies were achieved, compared with 10 in the CC/hMG group. Only four cycles were cancelled in the GnRHa group, vis-a-vis 13 in the CC/hMG group, a significant difference. The study showed that prolonged use of GnRHa as a preparatory treatment is effective following previous failures of IVF.
Transfer of multiple embryos in in vitro fertilization (IVF) requires recruitment and maturation of many follicles prior to oocyte retrieval. To achieve this, controlled ovarian hyperstimulation (COH) with gonadotropins is used, often in combination with clomiphene citrate (CC). Accurate timing of oocyte retrieval is of the utmost importance, since too early retrieval may result in immature oocytes which will not fertilize. O n the other hand, too long a wait will lead to a spontaneous L H surge with ensuing ovulation. Some IVF groups use identification of the spontaneous L H surge for timing of oocyte retrieval, but this requires repeated LH measurements. Therefore most groups induce ovulation with human chorionic gonadotropin (hCG), accepting the risk of spontaneous surge prior to the effect of hCG. With these stimulation procedures, 10-30% of the cycles are cancelled prior to oocyte retrieval, the most frequent causes being poor ovarian response, premature luteinization and spontaneous ovulation( 1 4 ) . Fleming and Coutts demonstrated that in gonadotropin-stimulated IVF cycles, premature luteinization due to fluctuating L H levels occurred in about half of the cycles, and that premature luteinization and spontaneous LH surges could be almost abol22
ished by using a gonadotropin-releasing hormone agonist (GnRHa) in conjunction with human menopausal gonadotropin (hMG) (4). Subsequent studies on the use of different G n R H a preparations and various treatment protocols have reported improved results with respect to number of cancellations and pregnancy rates per cycles initiated in selected groups where COH previously had failed (1, 5-8).
In order to evaluate a fixed time G n R H a regimen for IVF, the results of GnRHa/hMG stimulation in a group consisting of patients with previously failed stimulation cycles were compared with results from patients who received CClhMG stimulation in their first IVF cycle. MATERIAL AND METHODS During a 6-month period, treatment with a GnRHa prior to and during stimulation with hMG for IVF was given to 51 patients in 54 cycles, the GnRHa group. All patients had previously undergone 1-3 IVF attempts using hMG only or
CC/hMG for COH, none of which resulted in a pregnancy. Of 112 previous IVF cycles in the GnRHa group, 53 were cancelled due to either poor response (29) or spontaneous ovulation (24). A poor response cycle was defined as fewer than three follicles 2 15 mm in diameter or an estradiol level < 3 nmol/l on the day of ovulation induction with Acta Obstet Gynecol Scnnd 69 (19yo)
334
T. Tanbo et al.
Table I. Patient characteristics (per cycle) in the GnRHa and CC/hMG groups GnRHa
CClhMG
group (n=54)
group (n=47)
P
Age
33.9k3.7 31.5k2.7
OVARIAN HYPERSTIMULATION FOR IN VITRO FERTILIZATION PRECEDED BY PROLONGED ADMINISTRATION OF A GONADOTROPIN-RELEASING HORMONE AGONIST Tom Tanbo, Per Olav Dale and Thomas Abyholm From the Department of Obstetrics and Gynecology, the National Hospital, University of Oslo, Oslo, Norway
Abstract. In 51 patients, controlled ovarian hyperstimulation with clomiphene citrate (CC)/human menopausal gonadotropin (hMG), or hMG only, in 702 IVF cycles had previously resulted in a cancellation rate of 52% and no pregnancies. In 54 subsequent cycles the women were treated with prolonged administration of a gonadotropin-releasing hormone agonist (GnRHa) followed by hMG stimulation, the GnRHa group. The results were compared with the outcome of 47 cycles in patients who came for their first IVF attempt. In this group a CClhMG regimen was used, the CClhMG group. In the GnRHa group, 17 pregnancies were achieved, compared with 10 in the CC/hMG group. Only four cycles were cancelled in the GnRHa group, vis-a-vis 13 in the CC/hMG group, a significant difference. The study showed that prolonged use of GnRHa as a preparatory treatment is effective following previous failures of IVF.
Transfer of multiple embryos in in vitro fertilization (IVF) requires recruitment and maturation of many follicles prior to oocyte retrieval. To achieve this, controlled ovarian hyperstimulation (COH) with gonadotropins is used, often in combination with clomiphene citrate (CC). Accurate timing of oocyte retrieval is of the utmost importance, since too early retrieval may result in immature oocytes which will not fertilize. O n the other hand, too long a wait will lead to a spontaneous L H surge with ensuing ovulation. Some IVF groups use identification of the spontaneous L H surge for timing of oocyte retrieval, but this requires repeated LH measurements. Therefore most groups induce ovulation with human chorionic gonadotropin (hCG), accepting the risk of spontaneous surge prior to the effect of hCG. With these stimulation procedures, 10-30% of the cycles are cancelled prior to oocyte retrieval, the most frequent causes being poor ovarian response, premature luteinization and spontaneous ovulation( 1 4 ) . Fleming and Coutts demonstrated that in gonadotropin-stimulated IVF cycles, premature luteinization due to fluctuating L H levels occurred in about half of the cycles, and that premature luteinization and spontaneous LH surges could be almost abol22
ished by using a gonadotropin-releasing hormone agonist (GnRHa) in conjunction with human menopausal gonadotropin (hMG) (4). Subsequent studies on the use of different G n R H a preparations and various treatment protocols have reported improved results with respect to number of cancellations and pregnancy rates per cycles initiated in selected groups where COH previously had failed (1, 5-8).
In order to evaluate a fixed time G n R H a regimen for IVF, the results of GnRHa/hMG stimulation in a group consisting of patients with previously failed stimulation cycles were compared with results from patients who received CClhMG stimulation in their first IVF cycle. MATERIAL AND METHODS During a 6-month period, treatment with a GnRHa prior to and during stimulation with hMG for IVF was given to 51 patients in 54 cycles, the GnRHa group. All patients had previously undergone 1-3 IVF attempts using hMG only or
CC/hMG for COH, none of which resulted in a pregnancy. Of 112 previous IVF cycles in the GnRHa group, 53 were cancelled due to either poor response (29) or spontaneous ovulation (24). A poor response cycle was defined as fewer than three follicles 2 15 mm in diameter or an estradiol level < 3 nmol/l on the day of ovulation induction with Acta Obstet Gynecol Scnnd 69 (19yo)
334
T. Tanbo et al.
Table I. Patient characteristics (per cycle) in the GnRHa and CC/hMG groups GnRHa
CClhMG
group (n=54)
group (n=47)
P
Age
33.9k3.7 31.5k2.7
