A prospective, randomized controlled trial comparing the efficacy of recombinant follicle-stimulating hormone in three different in vitro fertilization protocols.

OBJECTIVE: To compare the following IVF protocols: a short protocol and long protocols starting on day 2 or day 21. All protocols used recombinant FSH (rFSH) for ovarian stimulation. DESIGN: Prospective, randomized study. SETTING: An assisted reproduction unit at a university center. PATIENT(S): Patients undergoing IVF (n = 150) were treated according to one of the three treatment protocols allocated by a random method. INTERVENTION(S): All patients used buserelin acetate and rFSH. Patients began the long protocol on day 2 (group 1) or day 21 (group 2) of the cycle. Patients in group 3 began the short protocol on day 2 of the cycle. MAIN OUTCOME MEASURE(S): Ovarian response, implantation rates, and pregnancy rates (PRs). RESULT(S): Patients treated with the short protocol (group 3) were stimulated in a shorter time, required less rFSH, and achieved higher E(2) levels. The numbers of follicles, oocytes, and embryos were similar in all three groups. The implantation rates were similar in groups 1 and 2 (11.8% and 13.3%, respectively), and both were higher than in group 3 (4.1%). Clinical PRs per oocytes retrieved were 19.6%, 18.6%, and 8.3% in groups 1, 2, and 3, respectively. CONCLUSION(S): The implantation rate was significantly higher with the long protocols than with the short protocol, with a tendency for a higher PR as well.

The significance of delayed suppression using buserelin acetate and recombinant follicle-stimulating hormone in a long protocol in vitro fertilization program.

OBJECTIVE: To determine whether the time taken to achieve ovarian suppression has an impact on ovarian responsiveness and the outcome of IVF-ET. DESIGN: Retrospective analysis. SETTING: An assisted reproduction unit at a university center. PATIENT(S): Patients undergoing a long protocol of IVF-ET that included buserelin acetate therapy initiated on day 2 of the cycle and recombinant FSH. INTERVENTION(S): Patients were divided into two groups according to the duration of buserelin acetate therapy required to achieve pituitary and ovarian suppression (group 1 = 2 weeks, n = 172; group 2 = > or =3 weeks, n = 337). MAIN OUTCOME MEASURE(S): Number of recombinant FSH ampules administered, duration of ovarian stimulation (days), ovarian response, and IVF outcome. RESULT(S): The patients in group 2 had lower mean E2 levels after 5 days and 9 days of stimulation than the patients in group 1. The number of recombinant FSH ampules administered and the number of days of stimulation required were higher in group 2 than in group 1. These differences were prominent in the subgroups of older patients (> or =36 years) and patients who had no evidence of polycystic ovaries on ultrasound examination. The number of oocytes retrieved and fertilized, the cancelation rate, and the pregnancy rate were similar in the two groups. CONCLUSION(S): Prolonged administration of a GnRH agonist to achieve suppression leads to a reduced ovarian response, particularly in women > or =36 years of age, but does not affect the success rate of IVF-ET.

The pubofascial anchor sling procedure for recurrent genuine urinary stress incontinence.

OBJECTIVE: To evaluate, in a preliminary study, the outcome of a modified pubovaginal sling operation with titanium bone anchors for recurrent genuine stress urinary incontinence (GSI) in women. PATIENTS AND METHODS: This prospective study included 13 consecutive women who underwent the modified sling procedure between September 1994 and August 1996. The subjective and objective cure of urinary stress incontinence, and the occurrence of postoperative osteitis pubis, were assessed. RESULTS: All 13 patients subjectively claimed complete urinary continence and 12 were objectively cured (12 patients agreed to undergo a repeat urodynamic study) during a median (range) follow-up of 26 (19-38) months. There were no cases of postoperative osteitis pubis, bladder injury or major complications. Mild suprapubic pain was a frequent and self-limiting complication. CONCLUSIONS: This innovative modified sling procedure is effective for recurrent urinary stress incontinence, with no complication of osteitis pubis. We suggest that this procedure should be considered as a treatment for recurrent GSI and perhaps for primary GSI. A study incorporating a longer follow-up and more patients has been planned.

Right or left ovary--which one is better?

This study tests the hypothesis that there is a different response after gonadotrophin-releasing hormone and human menopausal gonadotrophins (GnRH/HMG) stimulation for in-vitro fertilization (IVF) in patients with either a right or left ovary. A total of 56 cycles in 44 women after left oophorectomy (group A) was compared with 42 cycles in 29 women following right oophorectomy (group B). Tubal disease was the sole cause of infertility in all cases. The two groups were similar in age. There was no difference in total amount or days of HMG required for ovulation induction, peak oestradiol concentrations, number of oocytes retrieved and fertilization rate. The pregnancy rate was identical in the two groups (20.0 and 20.9% respectively). Our results indicate that with GnRH/HMG ovulation induction protocol for IVF there is no predilection of one ovary over the other.

Transsphenoidal resection in Cushing's disease: undetectable serum cortisol as the definition of successful treatment.

OBJECTIVE: We tested the hypothesis that in Cushing's disease, ACTH secretion from the normal pituitary surrounding an ACTH-secreting adenoma is inhibited and hence removal of the entire adenoma should result in an undetectable serum cortisol in the immediate post-operative period. DESIGN: A retrospective study of patients undergoing transsphenoidal selective adenomectomy, hemi-hypophysectomy or total hypophysectomy for Cushing's disease at St Bartholomew's Hospital between 1985 and 1990. PATIENTS: Forty-eight consecutive patients (33 women, mean age 43, range 7-69 years) undergoing transsphenoidal hypophysectomy for Cushing's disease. Ten patients who underwent a second operation were re-evaluated; the patients were followed for a median time of 40 months after operation (range 15-70). MEASUREMENTS: Post-operatively, serum cortisol was measured daily at 0900 h. Serum TSH, T4, prolactin, LH, FSH, testosterone or oestradiol plus plasma and urine osmolality were measured. RESULTS: After initial surgery, post-operative serum cortisol was undetectable (< 50 nmol/l) in 20 out of 48 patients (42%) and < 300 nmol/l in 32 out of 48 patients (67%). Re-exploration of the pituitary fossa in 10 patients found undetectable cortisol levels in 25 (52%) and levels < 300 nmol/l in 39 (81%) patients. Cushing's syndrome has not recurred, clinically or biochemically, in any patient in whom the post-operative cortisol was < 50 nmol/l. Post-operatively, hypothyroidism was present in 40% of patients and hypogonadism in 53% of men and 30% of premenopausal women. Diabetes insipidus, persisting for at least six months, occurred in 46% of patients. CONCLUSIONS: Cushing's disease has not recurred in any patient with an undetectable serum cortisol (< 50 nmol/l) post-operatively. Serum cortisol should be regarded as a tumour marker in Cushing's disease and the aim of transsphenoidal hypophysectomy for Cushing's disease should be to render the immediate post-operative serum cortisol undetectable.

Modulation of the human sperm acrosome reaction by effectors of the adenylate cyclase/cyclic AMP second-messenger pathway.

The acrosome reaction of spermatozoa appears to be analogous to various somatic cell exocytotic events which involve cascade reactions, i.e., transmission of an external signal across the cell membrane resulting in activation of an "amplifier" enzyme and the generation of a second messenger. Using a synchronous acrosome reaction system (De Jonge et al., J. Androl., 10:232-239, '89a), it was found that analogues of the second-messenger cAMP, dibutyryl cAMP (dbcAMP) and 8-bromo cAMP, stimulated the acrosome reaction of capacitated spermatozoa. Additionally, treatment of spermatozoa with either xanthine or non-xanthine phosphodiesterase inhibitors induced a significant (P less than 0.05) increase in the percent acrosome reaction after a period of capacitation in comparison to untreated controls. These results indicate that analogues of cAMP or inhibitors which prevent cAMP hydrolysis can induce the human sperm acrosome reaction. Subsequent experiments were conducted to test whether the amplifier enzyme in the cascade reaction, adenylate cyclase, has a role in the acrosome reaction. Forskolin, an adenylate cyclase stimulator, caused a significant (P less than 0.01) increase in the percent acrosome reaction in comparison to controls. Modulators of adenylate cyclase--adenosine, 2'-0-methyladenosine, and 2',3'-dideoxyadenosine--significantly (P less than 0.01) inhibited the forskolin-induced acrosome reaction. dbcAMP was able to overcome the inhibition by adenosine. Two inhibitors of protein kinase A, the Walsh inhibitor and H-8, caused a significant (P less than 0.01) inhibition of the dbcAMP-induced acrosome reaction. Finally, in the absence of extracellular calcium, dbcAMP induced a significant (P less than 0.01) increase in the acrosome reaction in contrast to A23187. These results suggest that: 1) a molecular mechanism for the human sperm acrosome reaction involves the cAMP second-messenger system; i.e., activation of adenylate cyclase, the amplifier enzyme that produces cAMP, production of cAMP as a second messenger, and activation of cAMP-dependent kinase A; and that 2) activation of adenylate cyclase occurs after calcium influx.

Post-operative deep vein thrombosis incidence in Nigerians.

In 450 consecutive Nigerian patients aged 20 and above undergoing elective surgery, the incidence of post-operative deep vein thrombosis using clinical methods was 2.2 per cent. Of these 333 were men and 5 had deep vein thrombosis giving an incidence of 1.5 per cent while 117 were females and 5 had deep thrombosis giving an incidence of 4.3 per cent. This figure is low and appears to agree with the current opinion that post operative deep vein thrombosis is comparatively rare in Africans. This is in contrast to the view expressed by Nwokolo and Ikoku (1967) that thromboembolic disease is more common in Nigeria than in East and Central Africa.