Seang-Lin Tan

Hypersecretion of luteinising hormone: a significant cause of infertility and miscarriage

Tonic hypersecretion of luteinising hormone (LH) occurs only in women with the polycystic ovary syndrome (PCOS), a common condition affecting both fertility and pregnancy outcome. In particular, the finding of an elevated serum LH concentration has been associated with an increased risk of infertility and miscarriage. The precise role of LH in the pathogenesis of infertility and miscarriage is still being debated. Similarly, several hypotheses exist to explain the mechanisms that lead to perturbed LH secretion. Treatment strategies have been developed to suppress serum LH levels, although whether they have a beneficial effect on conception and miscarriage rates is still uncertain. We shall review these topics in what is presently a controversial but increasingly important area of reproductive medicine.

Stimulation of oxidant generation by human sperm suspensions using phorbol esters and formyl peptides: relationships with motility and fertilization in vitro.

OBJECTIVES To investigate the influence of reactive oxygen species generated by human spermatozoa and contaminating leukocytes on sperm movement and fertilization in vitro. DESIGN A chemiluminescence technique, using luminol and peroxidase, was used to monitor the generation of reactive oxygen species by human sperm suspensions and the results were correlated with sperm movement and the fertilization of human ova in vitro. SETTING Diagnostic Andrology Laboratory and IVF Clinic. PATIENTS Infertile couples undergoing IVF therapy. RESULTS An N-formyl-methionyl-leucyl-phenylalanine (FMLP) provocation test was used to demonstrate that the presence of leukocytes in 28.5% of the sperm preparations was associated with elevated levels of spontaneous reactive oxygen species production, impaired movement, and a reduced capacity for fertilization in vitro. In the absence of leukocytes, exposure to phorbol ester stimulated a burst of reactive oxygen species generation by human spermatozoa, the magnitude of which was correlated highly with a loss of sperm motility but not with fertilization rates observed in the concurrent IVF cycle. CONCLUSION Leukocyte contamination of human sperm preparations can be detected readily by FMLP-induced, luminol-dependent chemiluminescence and the results have an important bearing on the fertilizing capacity of the spermatozoa in vitro.

A prospective randomized study of the optimum timing of human chorionic gonadotropin administration after pituitary desensitization in in vitro fertilization

Objective To determine if there is an optimum time for the administration of human chorionic gonadotropin (hCG) after pituitary desensitization with gonadotropin-releasing hormone agonists (GnRH-a) has been achieved before ovarian stimulation for in vitro fertilization (IVF). Design Prospective randomized study. Patients Two hundred forty-seven patients undergoing an IVF treatment cycle who were randomly divided into three groups. Interventions All patients were administered subcutaneously buserelin acetate 500 μ g/d from day 1 of the menstrual cycle. After pituitary desensitization had been achieved at least 14days later, ovarian stimulation with human menopausal gonadotropin was commenced. Ovarian stimulation, cycle monitoring, oocyte recovery, and IVF and embryo transfer (ET) techniques were identical in all three groups. Patients in group 1 (n=79) had hCG administered when the mean diameter of the largest follicle had reached 18mm, at least two other follicles were >14mm, and serum estradiol (E 2 ) levels were consistent with the number of follicles observed on ultrasound. Patients in groups 2 (n=84) and 3 (n=84) had hCG administered 1day and 2days, respectively, after the above criteria had been reached. Results The mean day of hCG administration ( P 2 concentration ( P =0.06), number of days of serum E 2 rise ( P =0.03), and mean diameter of the largest follicle ( P Conclusions There is no significant advantage in the precise timing of hCG administration after pituitary desensitization with GnRH-a.

The administration of glucocorticoids for the prevention of ovarian hyperstimulation syndrome in in vitro fertilization: a prospective randomized study

OBJECTIVE To determine if the administration of glucocorticoids reduced the rate of ovarian hyperstimulation syndrome (OHSS) in high-risk patients after ovarian stimulation for in vitro fertilization (IVF). DESIGN Prospective randomized study. PATIENTS Thirty-one patients who were stimulated with human menopausal gonadotropin (hMG) after pituitary desensitization by gonadotropin-releasing hormone agonist and who developed greater than 20 follicles greater than 12 mm and/or had a serum estradiol (E2) level of greater than 10,000 pmol/L on the day of administration of human chorionic gonadotropin (hCG). INTERVENTIONS Patients were randomly divided into two groups. Those who were randomized to receive glucocorticoids (group A) (n = 17) were administered intravenous hydrocortisone, 100 mg, immediately after ultrasound (US)-directed oocyte recovery. Prednisolone, 10 mg three times per day, was given for 5 days starting on the day of oocyte recovery followed by prednisolone 10 mg two times a day for 3 days and 10 mg/d for 2 days. Those in group B (n = 14) did not receive any glucocorticoid treatment. In both groups, luteal support was provided by intramuscular injections of gestone 100 mg/d. RESULTS The two groups of patients were comparable in terms of age, duration of infertility, and total dose of hMG used. All had polycystic ovaries on US examination. On the day of hCG administration, the mean number of follicles in the two groups were 26.76 +/- 2.49 and 25.93 +/- 1.44 and the serum E2 concentration 13,404 +/- 710 and 13,915 +/- 901 pmol/L, respectively. There were no significant differences in the number of oocytes collected or in the fertilization, cleavage, and implantation rates in the two groups. The pregnancy rates per initiated cycle were 41.18% and 35.71%, respectively. Seven of the 17 patients (41.2%) who received glucocorticoids developed ovarian hyperstimulation syndrome compared with 6 of the 14 patients (42.9%) who did not receive glucocorticoids. CONCLUSIONS Administrations of glucocorticoids to high risk patients did not reduce the rate of OHSS after ovarian stimulation for IVF.

Comparison of natural with clomiphene citrate-stimulated cycles in in vitro fertilization: a prospective, randomized trial *

OBJECTIVE To compare the outcome of natural with clomiphene citrate (CC)-stimulated cycles in IVF. DESIGN Prospective, randomized study. SETTING Tertiary referral center for assisted conception. SUBJECTS Thirty patients randomized to receive either no treatment (n = 14) or CC, 100 mg, from days 2 to 6 (n = 16). INTERVENTIONS Daily ultrasound (US) scan and measurements of serum LH and E2. Ovarian morphology was assessed on baseline US scan. Human chorionic gonadotrophin was administered when the mean diameter of the dominant follicle reached 17 mm. Transvaginal US-directed oocyte recovery was performed 35 hours later. MAIN OUTCOME MEASURES The number of patients reaching oocyte recovery; numbers of oocytes collected, fertilized and embryos transferred; and clinical pregnancy and multiple pregnancy rates (PRs) were recorded. RESULTS Ten cycles in the natural cycle group were abandoned before oocyte recovery compared with none in the CC group. There were significantly more follicles > 14 mm (2.4 +/- 0.3 [SE] compared with 0.9 +/- 0.2) and higher peak levels of E2 (375 +/- 67 pg/mL (1,378 +/- 247 pmol/L) compared with 204 +/- 17 pg/mL (748 +/- 61 pmol/L)) in those receiving CC compared with those receiving no drug. All 16 patients treated with CC had oocyte retrieval (mean, 1.8 +/- 0.3 oocytes) compared with only 4 in the natural cycle group (1 oocyte each). The oocyte recovery rate was 95%. Two patients conceived in the CC group (PR per ET, 18%) compared with none in the natural cycle group. Patients with polycystic ovaries developed more large follicles than those with normal ovaries. No patient developed ovarian hyperstimulation syndrome. CONCLUSIONS Patients undergoing natural cycle IVF are more likely to have abandoned cycles, produce fewer follicles and oocytes, and are less likely to reach ET than patients treated with CC alone. Clomiphene citrate should be considered for use in the context of a conventionally organised IVF-ET program if a mild degree of ovarian stimulation is desired.

A prospective randomized study comparing aspiration only with aspiration and flushing for transvaginal ultrasound-directed oocyte recovery

OBJECTIVE To compare aspiration only with aspiration and flushing of ovarian follicles during transvaginal ultrasound (US)-directed oocyte recovery. DESIGN Prospective randomized study. PATIENTS One hundred patients who were undergoing an in vitro fertilization (IVF) treatment cycle. INTERVENTIONS All patients underwent pituitary desensitization before the administration of gonadotropins. Monitoring of ovarian stimulation and the criteria for the administration of human chorionic gonadotropin were similar in both groups. In patients in whom aspiration alone was used, each follicle was aspirated until it was empty. The US probe was then rotated until every drop of follicular fluid had been aspirated before the next follicle was aspirated and the procedure repeated. For patients who had aspiration and flushing, each follicle was aspirated and then flushed up to a maximum of six times before moving to the next follicle. In both groups, all follicles greater than 10 mm were aspirated. RESULTS The indication for IVF and mean age of the patients were comparable in the two groups. There were no significant differences between the aspiration and the aspiration and flushing groups in terms of the number of oocytes retrieved (11 versus 9), the oocyte recovery rates (77.5% versus 77.0%), the fertilization rates (55.6% versus 60.0%), the number of embryos transferred (2 versus 2), or the number of clinical pregnancies (12 versus 13). The time taken for oocyte recovery was significantly shorter (15 versus 30 minutes, P less than 0.00001), and the dose of pethidine required significantly less (50 mg versus 100 mg, P less than 0.00001) in the aspiration only group. CONCLUSIONS Aspiration alone produces comparable oocyte recovery rates as aspiration and flushing while significantly reducing the length of the procedure and the dose of analgesia required. Aspiration alone suffices for virtually all cases during transvaginal US-directed oocyte recovery.

The routine use of gonadotropin-releasing hormone agonists for all patients undergoing in vitro fertilization. Is there any medical advantage? A prospective randomized study.

Objective To determine if the routine use of gonadotropin-releasing hormone agonists (GnRH-a) for all patients undergoing in vitro fertilization (IVF) produces any significant medical advantage. Design Prospective randomized study. Patients Three hundred eight patients having their first ever IVF attempt. Interventions Patients were randomly divided into four groups and received either human menopausal gonadotropin (hMG) alone for ovarian simulation (group A, n=81); clomiphene citrate and hMG (group B, n=77); a 3-day ultrashort course of GnRH-a and hMG (group C, n=74); or pituitary desensitization with GnRH-a followed by hMG (group D, n=76). Results The indications for IVF and mean age of all four groups of patients were comparable. There was a significant difference in the number of embryos cleaved and transferred among the groups, but there were no significant differences in the cancellation rate, mean number of oocytes collected or fertilized, and number of cases of failed fertilization. There were also no significant differences in the pregnancy and live birth rates per cycle commenced or per embryo transfer. Conclusion The routine use of GnRH-a for all patients undergoing IVF has practical but no significant medical advantages.

A prospective study comparing the outcome of oocytes retrieved in the aspirate with those retrieved in the flush during transvaginal ultrasound directed oocyte recovery for in‐vitro fertilization

Objective To study prospectively the fate of oocytes collected from the follicular aspirate and subsequent flushes during transvaginal ultrasound directed oocyte recovery for in‐vitro fertilization (IVF).

Successful in vitro fertilization and embryo transfer after treatment of invasive carcinoma of the breast

Carcinoma of the breast is the most common female malignancy and may occasionally affect women in the reproductive age group. We report a patient who had primary infertility after surgical extirpation of breast carcinoma. Successful pregnancy and delivery of a healthy baby were achieved after two cycles of IVF-ET therapy.

Transvaginal peritoneal oocyte and sperm transfer for the treatment of nontubal infertility

OBJECTIVE To investigate if peritoneal oocyte and sperm transfer (POST) performed transvaginally is an effective treatment for nontubal infertility. DESIGN, SETTING, AND PATIENTS Prospective study of 18 patients (4 with unexplained infertility, 13 with failed donor insemination, and 1 with male factor infertility) having 20 cycles of transvaginal POST in a specialist infertility unit. INTERVENTIONS Ovarian stimulation was achieved with human menopausal gonadotropin (hMG) alone, hMG and clomiphene citrate, or gonadotropin-releasing hormone agonist with hMG. Oocyte recovery was performed transvaginally under ultrasound guidance, the pouch of Douglas rinsed repeatedly and an embryo transfer catheter used to transfer 4 x 10(6) progressively motile sperm in 1 mL and up to four oocytes into the pouch of Douglas. Luteal support was provided with human chorionic gonadotropin injections given 2 and 5 days later. RESULTS The mean age of the patients was 32.65 +/- 5.0, and the mean length of infertility 5.07 +/- 2.32 years. The mean number of oocytes transferred was 3.53 +/- 0.87. Three pregnancies were achieved in the failed donor insemination group and 1 each in those with unexplained and male factor infertility, giving overall clinical pregnancy and live birth rates of 25% and 20% per initiated cycle. All pregnancies were achieved in those who had three or four oocytes transferred. CONCLUSION Transvaginal POST is a useful assisted conception technique for the treatment of nontubal infertility.