Induction of single ovulation by sequential follicle-stimulating hormone and pulsatile gonadotropin-releasing hormone treatment

Kuwahara, Akira; Matsuzaki, Takashi; Kaji, Hiroyuki; Irahara, Minoru; Aono, Toshihiro

doi:10.1016/s0015-0282(16)57721-8

“…Consistent with pharmacokinetic studies (11,12), the overall median serum FSH concentration in the low dose step-up group remains fairly stable in the late follicular phase. Another study in which exogenous FSH was replaced by pulsatile administration of GnRH when dominant follicle growth was first recognized showed that multiple follicle growth was minimized, and a low multiple pregnancy rate could be obtained (30). The decrease in serum FSH during step-down ovulation induction in a protocol that combined exogenous gonadotropins with GnRH agonists showed a more pronounced median decrease of 10%/day (20) compared to the 5% daily decrease demonstrated in the present study.…”

Section: Knowledge Regarding the Interplay Between Serum Fsh Levels A...supporting

confidence: 39%

Urinary Follicle-Stimulating Hormone for Normogonadotropic Clomiphene-Resistant Anovulatory Infertility: Prospective, Randomized Comparison between Low Dose Step-Up and Step-Down Dose Regimens

Santbrink¹

1997

Journal of Clinical Endocrinology & Metabolism

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A low dose step-up and step-down regimen for induction of ovulation using urinary FSH was compared in a prospective randomized fashion in 37 normogonadotropic clomiphene-resistant oligo- or amenorrheic infertile women. The objectives was to assess potential differences in duration of treatment, ovarian stimulation (serum FSH levels), and response [serum estradiol (E2) levels and number and size of follicles]. Monitoring (blood sampling and transvaginal sonography) took place on the day of initiation of treatment, the first day of ovarian response as assessed by ultrasound (i.e. the first day a follicle > or = 10 mm could be recognized), the day of hCG administration to induce ovulation, and 3 days thereafter. The median duration of treatment in the low dose step-up group was 18 (range, 7-41) days compared to 9 (range, 4-16) days in the step-down group (P = 0.003), and the total numbers of ampules administered were 20 (range, 7-69) and 14 (range, 7-33), respectively (P = NS). Serum FSH levels from the first day of sonographic ovarian response until the administration of hCG were constant (median increase, 2%/day) in patients receiving the low dose step-up protocol, but showed a decrease (median, 5%/day) in step-down cycles (P < 0.001). Monofollicular growth, defined as not more than one follicle 16 mm or larger on the day of hCG administration, was observed in 56% of low dose step-up and 88% of step-down cycles (P = 0.04). The percentage of patients with normal range periovulatory E2 serum levels (500-1500 pmol/L) was 33% in the low dose step-up group vs. 71% in the step-down group (P = 0.03). We conclude that a step-down protocol for gonadotropin induction of ovulation exhibits a more physiological, late follicular phase FSH serum profile than a low dose step-up protocol. This results in a shorter duration of treatment, a greater number of monofollicular cycles, and more cycles with periovulatory E2 levels within the normal range in the step-down protocol.

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“…These studies have shown that the late follicular phase FSH profile during a step-down dose regimen with initial doses of two ampules per day and decreasing steps of a half-ampule per day closely resembles serum FSH levels of the spontaneous cycle (20,21), and that treatment outcome is at least comparable to that using low dose step-up protocols (22). Another study in which exogenous FSH was replaced by pulsatile administration of GnRH when dominant follicle growth was first recognized showed that multiple follicle growth was minimized, and a low multiple pregnancy rate could be obtained (30). The results obtained indicate that in the step-down group, serum FSH levels decrease in the late follicular phase in all patients (median, 5%/day), whereas in the low dose step-up group, individual serum FSH levels decrease in only 39% of patients (P Ͻ 0.001).…”

Section: Discussionmentioning

confidence: 74%

Urinary Follicle-Stimulating Hormone for Normogonadotropic Clomiphene-Resistant Anovulatory Infertility: Prospective, Randomized Comparison between Low Dose Step-Up and Step-Down Dose Regimens1

Santbrink¹,

Fauser²

1997

The Journal of Clinical Endocrinology &Amp; Metabolism

36

3

0

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A low dose step-up and step-down regimen for induction of ovulation using urinary FSH was compared in a prospective randomized fashion in 37 normogonadotropic clomiphene-resistant oligo- or amenorrheic infertile women. The objectives was to assess potential differences in duration of treatment, ovarian stimulation (serum FSH levels), and response [serum estradiol (E2) levels and number and size of follicles]. Monitoring (blood sampling and transvaginal sonography) took place on the day of initiation of treatment, the first day of ovarian response as assessed by ultrasound (i.e. the first day a follicle > or = 10 mm could be recognized), the day of hCG administration to induce ovulation, and 3 days thereafter. The median duration of treatment in the low dose step-up group was 18 (range, 7-41) days compared to 9 (range, 4-16) days in the step-down group (P = 0.003), and the total numbers of ampules administered were 20 (range, 7-69) and 14 (range, 7-33), respectively (P = NS). Serum FSH levels from the first day of sonographic ovarian response until the administration of hCG were constant (median increase, 2%/day) in patients receiving the low dose step-up protocol, but showed a decrease (median, 5%/day) in step-down cycles (P < 0.001). Monofollicular growth, defined as not more than one follicle 16 mm or larger on the day of hCG administration, was observed in 56% of low dose step-up and 88% of step-down cycles (P = 0.04). The percentage of patients with normal range periovulatory E2 serum levels (500-1500 pmol/L) was 33% in the low dose step-up group vs. 71% in the step-down group (P = 0.03). We conclude that a step-down protocol for gonadotropin induction of ovulation exhibits a more physiological, late follicular phase FSH serum profile than a low dose step-up protocol. This results in a shorter duration of treatment, a greater number of monofollicular cycles, and more cycles with periovulatory E2 levels within the normal range in the step-down protocol.

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“…Another interesting approach is the use of sequential treatment with FSH (starting dose two ampoules/day), followed by pulsatile GnRH administration (20 g pulses, subcutaneously, every 120 min) when the follicle reached a diameter of 11 mm. Results in 18 hypogonadotropic anovulatory patients were reported recently (348). Late follicular phase serum FSH levels were greatly diminished when pulsatile GnRH was applied, again resulting in a significant reduction in the number of large preovulatory follicles (1.3 vs. 3.9).…”

Section: February 1997mentioning

confidence: 94%

Manipulation of Human Ovarian Function: Physiological Concepts and Clinical Consequences

Fauser¹

1997

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Induction of single ovulation by sequential follicle-stimulating hormone and pulsatile gonadotropin-releasing hormone treatment

Cited by 7 publications

References 21 publications

Urinary Follicle-Stimulating Hormone for Normogonadotropic Clomiphene-Resistant Anovulatory Infertility: Prospective, Randomized Comparison between Low Dose Step-Up and Step-Down Dose Regimens

Urinary Follicle-Stimulating Hormone for Normogonadotropic Clomiphene-Resistant Anovulatory Infertility: Prospective, Randomized Comparison between Low Dose Step-Up and Step-Down Dose Regimens

Urinary Follicle-Stimulating Hormone for Normogonadotropic Clomiphene-Resistant Anovulatory Infertility: Prospective, Randomized Comparison between Low Dose Step-Up and Step-Down Dose Regimens1

Manipulation of Human Ovarian Function: Physiological Concepts and Clinical Consequences

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