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Different depot GnRH analogs (GnRH-A) are currently used for the reversible suppression of the pituitary-ovarian axis in several reproductive and neoplastic disorders in women. In spite of anecdotal reports of incomplete suppression by some depot GnRH-A, this issue has never been systematically investigated in adult women. Thus, we elected to study 40 normally cycling women with male-related infertility or benign reproductive disorders; each group of 10 subjects received a different GnRH-A for 3 months: buserelin (group B; 300 micrograms, sc, every 12 h, as a control), goserelin (group G; 3.6 mg, sc, every 28 days), leuprorelin (group L; 3.75 mg, im, every 28 days), and triptorelin (group T; 3.75 mg, im, every 28 days). Depot GnRH-A was administered by one of the investigators. GnRH tests (100 micrograms, iv) were performed before treatment (cycle day 7; test A) and on treatment days 57 (i.e. 1 day after the third depot GnRH-A; test B) and 84 (i.e. 28 days after the third depot GnRH-A; test C). Immunoreactive (i) LH levels were measured with an ultrasensitive immunochemiluminometric assay. Profound suppression of the iLH response to the GnRH test occurred in all subjects during treatment. Conversely, FSH levels in the third month of treatment tended to be higher in the depot GnRH-A groups than in group B, and this difference achieved statistical significance (P < 0.05) in groups G and L during test C. In GnRH test B, while the mean estradiol (E2) level was less than 75 pmol/L (< 20 pg/mL) in all group B subjects, individual E2 levels were greater than 75 pmol/L in five patients receiving depot GnRH-A (two in group G, one in L, and two in T). Finally, individual E2 levels during test C were greater than 75 pmol/L in only two patients of group G, who also reported vaginal spotting. Thus, we conclude that in adult women, 1) iLH was profoundly suppressed in the third month of administration of all GnRH-A tested; 2) FSH suppression with depot GnRH-A was less marked than that with high-dose short-acting sc buserelin; and 3) signs of an incomplete block of ovarian function can be present in the third month of depot GnRH-A administration, particularly when goserelin is employed.

Gonadotrophin-releasing hormone (GnRH) agonists have become irreplaceable addition to gonadotrophins in ovulation induction for assisted reproduction. Of the several schemes currently employed, long regimens appear to be maximally effective to optimize patient scheduling and to improve clinical results.

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The pattern of episodic gonadotrophin releasing hormone (GnRH)-driven luteinizing hormone (LH) secretion changes dynamically across the human menstrual cycle. Adherence to a specific regimen of pulse amplitude and frequency is critical for normal ovulation, menstrual cyclicity and reproductive function. Derangements of episodic LH secretion are associated with anovulation. We have shown that in the human slowing of GnRH-induced LH pulses results in lower ovulatory rates and dysfunctions of the mid-cycle LH surge. This information is relevant for the understanding of the endocrine dynamics of the menstrual cycle both in normal and anovulatory subjects.

Pulsatile GnRH (pGnRH) was administered to 292 anovulatory patients in 600 consecutive cycles between February 1984 and February 1993. This represents the largest single pGnRH series ever reported. Patients were divided into the following groups: primary hypogonadotropic amenorrhea (PHA), 73 patients, 161 cycles; other hypogonadotropic hypogonadisms (OHH), 57 patients 107 cycles; multifollicular ovary (MFO), 39 patients 75 cycles; polycystic ovary (PCO), 85 patients 172 cycles; and other hyperandrogenic anovulations (OHA), 38 patients 85 cycles. GnRH was administered iv at a dose of 1.25-20.0 micrograms every 30-120 min; most cycles (505) were performed with a regimen of 2.5-5.0 micrograms GnRH every 60-90 min. In 228 cycles of MFO, PCO, and OHA patients, pGnRH was preceded by GnRH agonist (GnRH-A) suppression. Ovulatory rates were 75%, and pregnancy occurred in 105 cycles (pregnancy rate of 18%/treatment cycle and 23%/ovulatory cycle). Ovulatory and pregnancy rates were higher in PHA, OHH, and MFO and lower in PCO and OHA. Only 4 multiple pregnancies occurred (3.8%), none after GnRH-A suppression. The abortion rate was 30% and was highest in PCO (45%). GnRH-A pretreatment improved ovulatory rates only in PCO (from 49% to 71%; P < 0.001), whereas it had no significant effect on pregnancy and abortion rates in any group. Higher weight and insulin were associated with lower ovulatory and pregnancy rates; higher LH and testosterone were associated with lower ovulatory rates only. We conclude that 1) pGnRH is a highly effective ovulation induction method; 2) pGnRH does not cause ovarian hyperstimulation; 3) low dose pGnRH is associated with a remarkably low incidence of multiple pregnancy; 4) GnRH-A pretreatment improves pGnRH outcome in PCO and further lowers the incidence of multiple pregnancy; 5) pGnRH is associated with relatively elevated abortion rates, particularly in PCO; and 6) pGnRH is less successful in overweight patients and when high baseline LH, testosterone, and insulin levels are present.

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