The use of a decremental dose regimen in patients treated with a chronic low-dose step-up protocol for WHO Group II anovulation: a prospective randomized multicentre study.

BACKGROUND: In women with chronic anovulation, the choice of the FSH starting dose and the modality of subsequent dose adjustments are critical in controlling the risk of overstimulation. The aim of this prospective randomized study was to assess the efficacy and safety of a decremental FSH dose regimen applied once the leading follicle was 10-13 mm in diameter in women treated for WHO Group II anovulation according to a chronic low-dose (CLD; 75 IU FSH for 14 days with 37.5 IU increment) step-up protocol. METHODS: Two hundred and nine subfertile women were treated with recombinant human FSH (r-hFSH) (Gonal-f) for ovulation induction according to a CLD step-up regimen. When the leading follicle reached a diameter of 10-13 mm, 158 participants were randomized by means of a computer-generated list to receive either the same FSH dose required to achieve the threshold for follicular development (CLD regimen) or half of this FSH dose [sequential (SQ) regimen]. HCG was administered only if not more than three follicles >or=16 mm in diameter were present and/or serum estradiol (E(2)) values were <1200 pg/ml. The primary outcome measure was the number of follicles >or=16 mm in size at the time of hCG administration. RESULTS: Clinical characteristics and ovarian parameters at the time of randomization were similar in the two groups. Both CLD and SQ protocols achieved similar follicular growth as regards the total number of follicles and medium-sized or mature follicles (>/=16 mm: 1.5 +/- 0.9 versus 1.4 +/- 0.7, respectively). Furthermore, serum E(2) levels were equivalent in the two groups at the time of hCG administration (441 +/- 360 versus 425 +/- 480 pg/ml for CLD and SQ protocols, respectively). The rate of mono-follicular development was identical as well as the percentage of patients who ovulated and achieved pregnancy. CONCLUSIONS: The results show that the CLD step-up regimen for FSH administration is efficacious and safe for promoting mono-follicular ovulation in women with WHO Group II anovulation. This study confirms that maintaining the same FSH starting dose for 14 days before increasing the dose in step-up regimen is critical to adequately control the risk of over-response. Strict application of CLD regimen should be recommended in women with WHO Group II anovulation.

[Oocyte and embryo quality in polycystic ovary syndrome]. / Qualité des ovocytes et embryons dans le syndrome des ovaires polykystiques.

OBJECTIVE: To compare oocyte and embryo quality in women with Polycystic Ovary Syndrome (PCOS) and in women with normal ovulation. PATIENTS AND METHODS: Forty women with PCOS underwent a total of 67 In Vitro Fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI) cycles. The control group consisted of women, of the same age, who underwent IVF (for tubal infertility) or ICSI (for male factor infertility) in the same period. RESULTS: The average number of oocytes recovered was higher in the PCOS group (12,1) than in the control group (9.6) as was the rate of immature oocytes (13.8% vs 5.8%; respectively). The fertilization rate was lower in PCOS patients (52% vs 61% in the controls). The cleavage rates, embryo morphology and pregnancy rates were similar in both groups. DISCUSSION AND CONCLUSIONS: Although more oocytes were recovered from PCOS patients, the number of good quality embryos, suitable for transfer or freezing was similar in the two groups as less of the oocytes were mature and the fertilization rate was lower in the PCOS group. IVF or ICSI (according to the indication) are therefore efficient in PCOS patients.

A comparative prospective study of a chronic low dose versus a conventional ovulation stimulation regimen using recombinant human follicle stimulating hormone in anovulatory infertile women.

The efficacy and safety of a chronic low dose (group A) and a conventional (group B) stimulation regimen of recombinant human follicle stimulating hormone (r-HFSH) were compared in 103 WHO Group II infertile women with clomiphene citrate-resistant anovulation. Mono- or bifollicular development was induced in 88.1% of patients in group A compared with 76.1% in group B. Ovulation and pregnancy rates were higher in group A (71.4% and 33.3%, respectively) than in group B (63.0% and 20%), but these differences were not statistically significant. Additionally, the total number of follicles that were >10 mm diameter was lower in group A than group B (3.0+/-2.6 versus 6.3+/-6.5; P < 0.0001), as was the oestradiol concentration (504+/-477 pg/ml versus 988+/-740 pg/ml; P < 0.03). The median dose of FSH (75 IU ampoules) used per cycle was 11 ampoules in group A and 12.5 in group B. In terms of the incidence of ovarian hyperstimulation syndrome, no differences were recorded between the two groups. The results demonstrated that r-HFSH is effective and safe in both these treatment protocols. The chronic low dose regimen was associated with a trend towards a higher rate of mono- or bifollicular development, without jeopardizing the incidence of pregnancy.

The kinetics of SHV-2 plasmid-mediated beta-lactamase compared to those of the parent enzyme from which it is derived.

Kinetic constants were determined for two closely related plasmid-mediated beta-lactamases: SHV-2 and PIT-2 (also known as SHV-1). These enzymes were synthesized constitutively. They were highly sensitive to the action of the inhibitors clavulanic acid and sulbactam, and they lacked activity against cephamycins and also imipenem. Both enzymes were significantly active against penicillins and first-generation cephalosporins, and the main difference concerned the third-generation cephalosporins: SHV-2 was highly active against these compounds whereas PIT-2 was not.

Results of planned in-vitro fertilization programming through the pre-administration of the oestrogen-progesterone combined pill.

The use of an oestrogen-progesterone combined pill permits the induction of ovulation in the absence of any developing follicle. Two treatments were compared. In the first, patients received no prior treatment before stimulation. In the second, combined oestrogen-progesterone treatment was given during approximately two menstrual cycles prior to stimulation. No differences between the two groups were found in relation to oocyte maturity, fertilization in vitro, cleavage, replacement and pregnancy. Fewer luteinizing hormone surges occurred in patients pre-treated with steroids. The utilization of the oestrogen-progesterone combined pill prior to induction of ovulation facilitates the forward planning of patients for in-vitro fertilization.

PIP: In order to facilitate the scheduling and management of cases for in vitro fertilization, a trial of pre-administration of a combined oral contraceptive was conducted. 103 women took 2 mg norethisterone acetate and 0.05 mg ethinyl estradiol for 45 to 70 days before induction of ovulation, allowing 5 days between treatments. This group then received either Clomid 100 mg for 6 days and HMG 225 IU on days 5, 7 and 9 (34 women), or HMG only (dose not specified, 69 women). The control groups were given identical ovulation induction regimens: Clomid and HMG (130 women) or HMG only (188 women). 70 of the patients selected for preliminary inhibition of ovulation had irregular menstrual cycles with normal prolactin; the others were picked for scheduling reasons only. No differences were documented between the groups in oocyte maturity, fertilization in vitro, cleavage, replacement and pregnancy. Pregnancy rates ranged from 10 to 16.6% in the 4 subgroups. Fewer LH surges occurred in patients pretreated with steroids. Thus the pretreatment of candidates for in vitro fertilization with ovulation blocking steroids has no quantitative effect on results, but does facilitate scheduling patients for the procedure.