Cumulative probability of clinical pregnancy and live birth after a multiple cycle IVF package: a more realistic assessment of overall and age-specific success rates?

OBJECTIVE: To provide an assessment of pregnancy and live birth probabilities for women presenting for in vitro fertilisation treatment for the first time, when committed in advance to have up to three cycles of treatment in one year. DESIGN: Up to three cycles of in vitro fertilisation within one year, committed in advance. SETTING: A tertiary referral centre for assisted reproduction. PARTICIPANTS: Two hundred and thirty-two women, undergoing a total of 536 cycles of in vitro fertilisation or intracytoplasmic sperm injection between August 1993 and December 1995. METHODS: Analysis of cumulative clinical pregnancy and live birth rates for women having IVF treatment for the first time and undertaking a three-cycle package, using the life-table approach. MAIN OUTCOME MEASURES: Cumulative clinical pregnancy and live birth rates. RESULTS: The cumulative probabilities of clinical pregnancy and live birth after two cycles of treatment were 38.2% and 33.2%, respectively, compared with 54.2% and 48.2%, respectively, after three cycles of treatment. Cumulative clinical pregnancy and live birth rates after three cycles of treatment for women up to the age of 40 years were 57.8% and 51.3%, respectively. Cumulative clinical pregnancy and live birth rates declined with increasing age (P = 0.02 and P= 0.01, respectively). CONCLUSION: The three-cycle package encourages couples to have multiple treatment cycles, thereby improving their ultimate chances of a live birth. The cumulative clinical pregnancy and live birth rates after such a package provide a more realistic assessment of overall and age-specific success rates after multiple treatment cycles.

Value of ovarian stromal blood flow velocity measurement after pituitary suppression in the prediction of ovarian responsiveness and outcome of in vitro fertilization treatment.

OBJECTIVE: To evaluate whether ovarian stromal blood flow velocity after pituitary suppression is predictive of ovarian response and the outcome of IVF treatment in patients with normal basal serum FSH levels and to compare the predictive value of this test with age, early follicular phase serum FSH level, E2 level, and FSH:LH ratio. DESIGN: Prospective observational study of women undergoing IVF treatment. SETTING: A tertiary referral center for assisted reproduction. PATIENT(S): Eighty-eight women who received the long buserelin acetate treatment protocol. INTERVENTION(S): Transvaginal color and pulsed Doppler measurement of the ovarian stromal peak systolic velocity (PSV) after pituitary suppression and measurement of the basal serum FSH level, E2 level, and FSH:LH ratio. MAIN OUTCOME MEASURE(S): Number of mature oocytes retrieved and pregnancy rate. RESULT(S): Ovarian stromal PSV was the most important single independent predictor of ovarian response in patients with a normal basal serum FSH level, when compared with age, basal FSH level, E2 level, or FSH:LH ratio. Patients in group 2 (PSV > or = 10 cm/s) had a significantly higher median number of mature oocytes retrieved (11 versus 5.5) and a higher clinical pregnancy rate (35.3% versus 11.3%) than patients in group 1 (PSV <10 cm/s), even after controlling for age. CONCLUSION(S): Ovarian stromal blood flow velocity, after pituitary suppression is confirmed, is predictive of ovarian responsiveness and the outcome of IVF treatment.

A prospective randomized study to assess the clinical efficacy of gonadotrophins administered subcutaneously and intramuscularly.

The purpose of this study was to compare the clinical efficacy of gonadotrophins administered s.c. or i.m., in a prospective randomized study of women undergoing in-vitro fertilization (IVF) treatment at a tertiary referral centre. In all, 71 patients undergoing a total of 162 IVF treatment cycles were randomized to receive either s.c. (n = 41) or i.m. (n = 30) administration of gonadotrophins. Up to three cycles of IVF were assessed for each patient. The main outcome measures were the number of oocytes retrieved, the total amount of gonadotrophins used, the number of follicles recruited and the cumulative pregnancy and live birth rates. The mean number of oocytes retrieved was 10.5 for each group. The number of days of stimulation was significantly shorter for the s.c. group (11.7 +/- 1.9 days, mean +/- SD) than the i.m. group (12.6 +/- 2.3 days). The cumulative conception and live birth rates after three cycles of treatment were similar between the two groups. Our results suggest that the clinical efficacy of s.c. and i.m. administration of gonadotrophins is comparable. Both routes are well tolerated by patients.

Local side effects of subcutaneous and intramuscular urinary gonadotropins for ovarian stimulation in in vitro fertilization: a prospective, randomized study.

OBJECTIVE: To compare the incidence and severity of local side effects of urinary-derived gonadotropins administered s.c. and i.m.. DESIGN: Prospective randomized study of women undergoing IVF treatment. SETTING: Tertiary referral center for assisted reproduction. PATIENT(S): A total of 71 patients were randomized to receive gonadotropins by the s.c. (n = 41) or i.m. (n = 30) route. INTERVENTION(S): One cycle of IVF with gonadotropins administered either s.c. or i.m. for ovarian stimulation. MAIN OUTCOME MEASURE(S): Incidence and severity of local side effects, such as redness, itching, swelling, pain, and bruising. RESULT(S): Pain was the most common side effect, with 55.3% and 70.1% of i.m. and s.c. injections, respectively, resulting in pain. There were no statistically significant differences in the incidence of itching or bruising after i.m. and s.c. injections. Although there was a higher incidence of redness and swelling in the s.c. group compared with the i.m. group, most cases were classified as mild. CONCLUSION(S): There was a significantly higher incidence of some local side effects after s.c. gonadotropin administration but most of these were mild and well tolerated by patients.

Implications of using follicle-stimulating hormone preparations depleted of luteinizing hormone to achieve follicular growth in in vitro fertilization.

We aimed to compare the outcome of in vitro fertilization (IVF) treatment using follicle-stimulating hormone (FSH) containing gonadotropins with human menopausal gonadotropin (hMG) containing gonadotropins for ovarian stimulation. A retrospective analysis of 82 patients undergoing IVF in a private fertility clinic was performed over a specific period of time. Eighteen women received hMG, 20 received Normegon and 44 received FSH. In addition, 17 of these patients received hMG in one cycle and FSH in the other. The main outcome measures studied were duration of treatment, dose of gonadotropins required to achieve optimum follicular growth, number and size of follicles, endometrial thickness, serum estradiol concentrations, number of oocytes retrieved, pregnancy rates and the incidence of ovarian hyperstimulation syndrome (OHSS). At the time of administration of human chorionic gonadotropin (hCG), the mean (+/- SD) serum estradiol concentrations in patients treated with preparations containing FSH and luteinizing hormone (LH) in a ratio of 1:1 was 10,044.3 +/- 5378.8 pmol/l compared with 6819.5 +/- 2597.9 pmol/l in patients treated with preparations with FSH and LH in a ratio of 3:1 and 7369 +/- 4300 pmol/l in patients treated with FSH. The differences between the first and the second two groups were significant (p < 0.05). Endometrial thickness in the three groups of patients were 11 +/- 1.7 mm, 11 +/- 1.5 mm and 9.7 +/- 1.5 mm, respectively (p < 0.001). Comparing cycles of treatment with hMG and FSH in the same patient, we found significantly higher estradiol levels, thicker endometrium, more developing follicles and a shorter duration of treatment in the hMG-treated cycles compared with those in FSH-treated cycles. However, there were no differences between the incidence of OHSS or the pregnancy rates between the three treatment groups. With the advent of recombinant human FSH and the shortage of LH-containing preparations, it is important to note that serum estradiol concentrations on the day of administration of hCG underrepresent the degree of follicular maturation. In the context of the use of a 'long' protocol of gonadotropin-releasing hormone (GnRH) analog therapy and LH-depleted gonadotropin preparations, serum estradiol is no longer a reliable marker of follicle development.

Natural spermatoceles in irreversible obstructive azoospermia--reservoirs of viable spermatozoa for assisted conception.

Fine needle aspiration of asymptomatic spermatoceles detected in five men with obstructive azoospermia was evaluated as a minimally invasive method of sperm retrieval for assisted conception. Sperm preparations adequate for in-vitro fertilization were initially obtained from three men, but there was failure of fertilization in all three cycles. However, intracytoplasmic sperm injection (ICSI) in three couples resulted in fertilization of 58% of metaphase II oocytes, with embryo transfers in five of six cycles. A successful pregnancy and delivery resulted from spermatozoa from a man with an irreversible vasectomy, for whom previous epididymal microaspiration and ICSI had been unsuccessful. Spermatoceles were found in 4% of men with irreversible obstructive azoospermia referred for assisted conception. These patients should therefore be examined very carefully for small cysts near the epididymis, because fine needle aspiration, usually without anaesthesia, can instantly locate a ready source of viable spermatozoa for ICSI. This is less invasive than the alternative sperm retrieval procedures, which are more traumatic and require local or general anaesthesia.

Comparison of intravenous albumin and transfer of fresh embryos with cryopreservation of all embryos for subsequent transfer in prevention of ovarian hyperstimulation syndrome.

OBJECTIVE: To compare the efficacy of administration i.v. albumin to prevent severe ovarian hyperstimulation syndrome (OHSS) in patients undergoing ovarian stimulation for IVF with a standard policy of cryopreserving all embryos and to assess the impact of the two methods of treatment on pregnancy rates (PRs). DESIGN: Prospective randomized study. SETTING: A tertiary referral center for assisted conception. PATIENTS: Twenty-six patients undergoing IVF treatment cycles who were considered to be at high risk of developing severe OHSS on the basis of their serum E2 concentrations on the day of hCG administration and the number of oocytes collected. INTERVENTION: In group 1 (n = 13) all the generated embryos were cryopreserved to be transferred subsequently in hormonally manipulated cycles. In group 2 (n = 13) patients received IV infusions of albumin on the day of oocyte retrieval and 5 days later. Patients in group 2 had transfers of fresh embryos. MAIN OUTCOME MEASURES: The total dosage of hMG used, total number of follicles developed, number of follicles > 14 mm in diameter, serum E2 concentrations and endometrial thickness on day of hCG administration, number of oocytes retrieved, number and quality of embryos generated, PRs per cycle commenced, and onset and degree of any OHSS developed. RESULTS: There were no significant differences in the above parameters between the two groups, except for PRs that were significantly higher in patients who had all embryos cryopreserved (38.6% versus 0%). CONCLUSION: The policy of cryopreserving all generated embryos appears as effective as the administration of i.v. albumin in preventing OHSS in high-risk patients and produces significantly higher PRs.

Outcome of frozen embryo replacement cycles following elective cryopreservation of all embryos in women at risk of developing ovarian hyperstimulation syndrome.

AIM: Our aim was to compare the outcome in subsequent frozen embryo replacement cycles in four groups of patients who had elective cryopreservation of all their embryos because they were considered to be at increased risk of developing severe ovarian hyperstimulation syndrome. DESIGN: Sixty-two (91%) of 68 IVF cycles (68 patients) in which elective cryopreservation of all embryos was performed were analyzed. All patients continued on the GnRH agonist, buserelin, after oocyte recovery until the onset of vaginal bleeding. Frozen embryo replacement occurred in a hormone replacement cycle that started either on day 3 of the withdrawal bleed (group I; N = 15) or after serum estradiol levels had fallen to < 100 pmol/L (group II; N = 16). The other patients commenced a frozen embryo replacement cycle several months later in either a hormone replacement (group III; N = 15) or a natural (group IV; N = 16) cycle. RESULTS: Two patients developed severe ovarian hyperstimulation syndrome. There were no significant differences among the four groups regarding demographic variables, the dose of hMG used, and the clinical outcome. There was a higher but not significantly different clinical pregnancy rate in group I (26.7%), compared to group II (12.5%), group III (13.3%), and group IV (18.8%). CONCLUSIONS: Several options exist for the timing and protocol used for frozen embryo replacement in patients who had elective cryopreservation for the prevention of ovarian hyperstimulation syndrome, none of which was found to be clearly superior in this observational report.

Success of intrauterine insemination using cryopreserved donor sperm is related to the age of the woman and the number of preovulatory follicles.

OBJECTIVE: Our objective was to assess parameters associated with a successful outcome of intrauterine insemination (IUI) using cryopreserved donor sperm. DESIGN: We analyzed 750 consecutive donor IUI cycles undertaken by 363 women in an assisted conception clinic. The main outcome measure was clinical pregnancy. RESULTS: IUI was performed in 94.7% of the 750 IUI treatment cycles commenced and 180 clinical pregnancies occurred. The clinical pregnancy rate per cycle was 26.4%. The rate was significantly related to the patient's age (30.5% for age < or = 35 years and 18.1% for age > 35 years; P < 0.006) and whether there was one or more than one preovulatory follicles [20.9, 34.4, and 31.5% for one, two, and three or four follicles with a mean diameter of 14 or more mm at the time of human chorionic gonadotropin (hCG) administration; P = 0.006]. Two to four preovulatory follicles were present in 12.6% of the natural cycles, 43.6% of clomiphene citrate or tamoxifen, and 59.9% of gonadotropin stimulated cycles. The difference in the number of preovulatory follicles between stimulated and unstimulated cycles was highly significant (P < 0.0001). Pregnancy rates were 29.9% in gonadotropin-stimulated cycles, 23.6% in clomiphene citrate- or tamoxifen-stimulated cycles, 23.6% in clomiphene and 20.1% in unstimulated cycles. The difference in pregnancy rates between gonadotropin-stimulated and natural cycles was significant (P = 0.038). Cycle fecundity rates were not significantly affected by the number of previous treatment cycles, duration of infertility, gravidity and parity of the patient, presence of a spontaneous luteinizing hormone (LH) surge before the administration of hCG, or number of motile sperm in the insemination specimen. CONCLUSIONS: Success of IUI using cryopreserved donor sperm is related to the age of the women and whether there is one or more than one preovulatory follicles.

Reliability of cardiotocography in predicting baby's condition at birth.

A prospective study of 6825 labours was undertaken to determine the relation between the Apgar scores of the babies at one minute and the cardiotocograph tracing in labour. The sensitivity of an abnormal tracing was 35.2% for babies who needed intermittent positive pressure ventilation and 20.0% for babies who did not but who had Apgar scores of less than 7. The sensitivity of an abnormal tracing for all babies with an Apgar score of less than 7 was 23.2%. The positive predictive value of an abnormal tracing was 8.7% for babies who needed intermittent positive pressure ventilation and 18.7% for babies who did not but who had an Apgar score of less than 7. The positive predictive value of an abnormal tracing was 27.4% for all babies with an Apgar score of less than 7. The specificity of the tracing was 93.4% for babies with an Apgar score of 7 or over. The relatively high incidence of false positive predictions might be explained on the grounds that abnormalities in the cardiotocograph tracing are a more sensitive indicator of hypoxia than the Apgar score. False negative predictions might have been due to adverse factors other than hypoxia--for example, fetal trauma, compression of the head, infection, and analgesia in labour. These findings suggest that the current overdependence on fetal monitoring by cardiotocography alone should be examined and that other reliable indicators for non-hypoxic fetal distress should be sought.