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P Pocognoli

Publications and source records attributed to P Pocognoli.

6 recordsLinked to original sources

Modulation of folliculogenesis and steroidogenesis in women by graded menotrophin administration.

BACKGROUND: To test the effects of progressively decreasing dosages of exogenous LH we combined various amounts of HMG, containing FSH, LH and HCG, and highly purified (HP) FSH to treat 120 GnRH agonist-suppressed infertile female patients as candidates for controlled ovarian stimulation (COS). METHODS: Subjects were randomly assigned to four treatment groups that received the following daily i.m. gonadotrophin regimens: A, FSH 150 IU only; B, FSH 150 IU and LH activity 37.5 IU; C, FSH 150 IU and LH activity 75 IU; D, FSH 150 IU and LH activity 150 IU. FSH dose adjustments were allowed only after the 14th treatment day. Monitoring included transvaginal ultrasound at 2-day intervals and daily determinations of LH, FSH, estradiol (E(2)), progesterone, testosterone and HCG. RESULTS: Duration of COS was significantly shortened in patients receiving at least 75 IU daily of LH activity. Small (<10 mm diameter) pre-ovulatory ovarian follicle occurrence was inversely correlated with LH activity dose administered (r = -0.648, P < 0.0001) and serum HCG levels (r = -0.272, P < 0.01) but not to serum LH levels. Serum testosterone levels were positively correlated to the LH activity dose administered (r = 0.313, P < 0.001), while serum progesterone levels were positively correlated to the FSH dose administered (r = 0.447, P < 0.00001) but not to the LH activity dose administered. CONCLUSIONS: Firstly, HCG content considerably contributes to HMG activity; secondly, menotrophin LH activity content can reduce in a dose-dependent manner the occurrence of small pre-ovulatory follicles; and finally, contrary to common belief, enhanced FSH stimulation rather than LH activity appears to cause premature follicle luteinization during COS.

Adult↗

Stimulation and growth of antral ovarian follicles by selective LH activity administration in women.

Intensive FSH stimulation is a key tool of assisted reproduction technology but can cause severe complications through the development of an excessive number of small ovarian follicles. We tested the hypothesis that, in the late stages of ovulation induction, LH activity in the form of low-dose human CG (hCG) can stimulate and selectively modulate ovarian follicle function and growth, independently of FSH administration. Four groups of GnRH agonist-suppressed normoovulatory women (10 each group) received recombinant human FSH (r-hFSH) (150 IU/d) for 7 d followed by: group A, r-hFSH 150 IU/d alone; group B, r-hFSH 50 IU/d and hCG 50 IU/d; group C, r-hFSH 25 IU/d and hCG 100 IU/d; group D, hCG 200 IU/d alone. Despite several days of lowered or absent r-hFSH administration, 70% of hCG-treated patients successfully completed treatment. In these subjects, preovulatory E2 levels and large (>14 mm diameter) ovarian follicle development were not reduced; conversely, the number of small (<10 mm diameter) ovarian follicles was significantly decreased in groups B-D vs. group A. Low-dose hCG administration did not cause follicle luteinization. We conclude that, following FSH priming, LH activity administration can: 1) stimulate folliculogenesis for several days, in spite of rapidly declining FSH levels; and 2) hasten small follicle demise. Therefore, LH activity administration could be used to design radically novel ovulation induction regimens that, by partly or completely replacing mid-/late follicular phase FSH administration, may reduce costs and improve safety of assisted reproduction technology.

Adult↗

Luteinzing hormone activity in menotropins optimizes folliculogenesis and treatment in controlled ovarian stimulation.

Although the role that LH plays in folliculogenesis is still controversial, recent evidence points toward facilitatory actions of LH activity in ovulation induction. Thus, we compared the response to either highly purified FSH (75 IU FSH/ampoule; group A, 25 subjects) or human menopausal gonadotropin (75 IU FSH and 75 IU LH/ampoule; group B, 25 subjects) in normoovulatory GnRH agonist-suppressed women, candidates for intrauterine insemination. A fixed regimen of 2 daily ampoules of highly purified FSH or human menopausal gonadotropin was administered in the initial 14 days of treatment; menotropin dose adjustments were allowed thereafter. Treatment was monitored with daily blood samples for the measurement of LH, FSH, 17beta-estradiol (E(2)), progesterone, testosterone, hCG, inhibin A, and inhibin B, and transvaginal pelvic ultrasound was performed at 2-day intervals. Although preovulatory E(2) levels were similar, both the duration of treatment (16.1 +/- 0.8 vs. 12.6 +/- 0.5 days; P< 0.005) and the per cycle menotropin dose (33.6 +/- 2.4 vs. 23.6 +/- 1.1 ampoules; P < 0.005) were lower in group B. In the initial 14 treatment days the area under the curve of FSH, progesterone, testosterone, inhibin A, and inhibin B did not differ between the 2 groups, whereas LH, hCG, and E(2) areas under the curve were higher in group B. The occurrence of small follicles (<10 mm) and the inhibin B/A ratio in the late follicular phase were significantly reduced in group B. A nonsignificant trend toward a higher multiple gestation rate was present in group A (60% vs. 17%). We conclude that ovulation induction with LH activity-containing menotropins is associated with 1) shorter treatment duration, 2) lower menotropin consumption, and 3) reduced development of small ovarian follicles. These features can be exploited to develop regimens that optimize treatment outcome, lower costs, and reduce occurrence of complications such as multiple gestation and ovarian hyperstimulation.

Adult↗

Luteinizing hormone activity supplementation enhances follicle-stimulating hormone efficacy and improves ovulation induction outcome.

Although FSH is essential to stimulate ovarian folliculogenesis, increasing physiological and clinical evidence suggests that moderate LH stimulation may also be critical for optimal follicle and oocyte development. Conversely, a clinical trend exists toward conducting controlled ovarian hyperstimulation (COH) in a LH-depleted environment, as recently developed gonadotropin preparations are devoid of LH activity, and endogenous LH is suppressed with GnRH analogs in most COH cycles. To investigate the role of LH activity during COH we supplemented highly purified (HP) FSH with low dose hCG in GnRH agonist-suppressed women. Twenty normoovulatory women were pretreated with a GnRH agonist and after 2 weeks were randomly assigned to receive HP FSH (150 IU/day) alone (group A; 10 patients) or combined with hCG (50 IU/day; group B; 10 patients). The HP FSH dose was increased after 14 days only in cases of inadequate response. Treatment was monitored with pelvic ultrasound and daily hormone determinations. None of the patients of group B and 8 of group A required more than 14 days of treatment and increments of the FSH dose. Folliculogenesis and 17beta-estradiol (E2) secretion progressed more rapidly and evenly in group B. Although preovulatory follicle number and E2 concentrations were comparable, patients in group B required a shorter stimulation time (12.5+/-0.6 vs. 17.3+/-0.7 days in group A; P < 0.0001) and a lower HP FSH dose (1725+/-84 vs. 2670+/-164 IU in group A; P < 0.0001). Serum levels of LH, E2, progesterone, and testosterone did not differ between the 2 groups; serum FSH was higher in group A. We conclude that LH activity promotes folliculogenesis in synergy with FSH in the mid- to late follicular phase and that low dose hCG coadministration optimizes COH by 1) enhancing FSH action, 2) accelerating ovarian follicle development, 3) shortening COH duration, 4) lowering HP FSH requirements, and 5) reducing COH cost. Thus, moderate LH activity in the follicular phase plays a positive physiological and clinical role in folliculogenesis and ovulation induction.

Adult↗

Subcutaneous administration of a depot gonadotropin-releasing hormone agonist induces profound reproductive axis suppression in women.

OBJECTIVE: To compare the i.m. and s.c. routes of depot GnRH agonist administration. DESIGN: Prospective, controlled pharmacokinetics study. SETTING: Volunteers in an academic research environment. PATIENT(S): Forty women with benign gynecologic disorders. INTERVENTION(S): Triptorelin administration (3.75 mg) at 28-day intervals for 6 consecutive months. Twenty patients were treated with IM triptorelin, and 20 patients were treated with SC triptorelin. MAIN OUTCOME MEASURE(S): Assessment of side effects, GnRH test results, and triptorelin, LH, FSH, estradiol, and progesterone levels. RESULT(S): The occurrence of injection site redness and itching and of some hypoestrogenic side effects was increased significantly in the SC group. Plasma triptorelin levels were significantly higher in the IM group in the first month of treatment; thereafter, the pattern reversed, with a nonsignificant trend toward higher plasma triptorelin levels in the SC group. Serum LH, FSH, estradiol, and progesterone levels were low after the first month of treatment and did not differ between the two treatment groups. On day 196 (2 months after the last depot triptorelin injection), triptorelin was still measurable and gonadotropins and gonadal steroids were still suppressed. Spontaneous menses returned significantly later in the SC group than in the IM group. CONCLUSION(S): Subcutaneous triptorelin can be administered by the patient. Both IM and SC triptorelin administration are cliniclly effective, but they result in different triptorelin pharmacokinetics. Subcutaneous triptorelin is associated with more prolonged amenorrhea than is IM triptorelin, suggesting enhanced pituitary-ovarian suppression. These results suggest that SC triptorelin may allow lower drug dosage administration and/or longer administration intervals.

Adult↗

Interaction between menstrual cyclicity and gonadotropin pulsatility.

Pulsatile gonadotropin secretion is a critical endocrine component of the regulation of the normal menstrual cycle. Pulsatile luteinizing hormone (LH) secretion changes dynamically across the menstrual cycle. Derangements of pulsatile LH secretion are found in virtually every menstrual disorder. This article summarizes the key features of pulsatile LH secretion in the normal menstrual cycle and in ovulatory disorders.

Female↗