Health-related quality of life in relation to gender and age in couples planning IVF treatment.

BACKGROUND: Specific subgroups of people planning IVF might be at risk of having more psychological or health-related problems. Identification of subgroups at risk may better enable allocation of appropriate counselling. METHODS: A group of 425 men and 447 women planning to undergo IVF treatment filled out a questionnaire. Four domains of health-related quality of life were measured, namely perceived emotional, physical, cognitive and social functioning. RESULTS: Young men and women (aged 21-30 years) planning IVF had more short-term social and emotional problems than people of the same age group in the general population. No substantial differences were found in cognitive and physical functioning for all age groups of men nor women planning IVF compared with the general population. A high level of irrational parenthood cognitions substantially accounted for a less optimal score on all the different domains of quality of life. These cognitions ('needing a child in order to live a happy life') were especially prevalent among younger women. CONCLUSIONS: Patients with high levels of irrational parenthood cognitions are at risk of a less optimal quality of life. A short cognitive counselling therapy is advised for patients with high levels of these cognitions.

[Results of in vitro fertilization in the Netherlands, 1996-2000]. / Resultaten van in-vitrofertilisatie in Nederland, 1996-2000.

OBJECTIVE: To describe the annual results in all 13 Dutch in vitro fertilisation (IVF) centres in the period 1996-2000, and to look for possible differences between individual centres and years. DESIGN: Retrospective data collection, description and analysis. METHOD: The results collected on the website of the Dutch Society of Obstetrics and Gynaecology (Dutch acronym: NVOG; www.nvog.nl) in the period 1996-2000 were integrated and described, with special attention to possible differences between centres and years. RESULTS: In 1996-2000 (5 years), 63,414 IVF or ICSI treatment cycles were started in the Netherlands, and 5,884 transfers of cryopreserved embryos were performed. The number of treatment cycles increased over the years, particularly the number of ICSI cycles. The total number of ongoing pregnancies was 12,991 (20.5% per started cycle; 22.5% for ICSI and 18.3% for IVF). Particularly during the first 3 years, there was an increase in these percentages (IVF: from 16.4% (1996) to 19.2% (1998); ICSI: from 18.3% (1996) to 23.9% (1998)). There were differences between the centres in both the percentage of ongoing pregnancies per started IVF/ICSI cycle (range 13.7-25.1%) and the percentage ICSI (14-61%) and cryo-transfers per total number of treatment cycles (0-26%). It was estimated that, during this 5-year period, 1 out of every 61 Dutch neonates resulted from IVF or ICSI. CONCLUSION: The pregnancy-rates after IVF and ICSI increased during the study period, and were comparable with the rates in other European countries. Some important data are still missing from the inventory, for example regarding the number of embryos per transfer, multiple pregnancies, live births, congenital malformations and complications.

A prospective, randomized clinical trial comparing 150 IU recombinant follicle stimulating hormone (Puregon((R))) and 225 IU highly purified urinary follicle stimulating hormone (Metrodin-HP((R))) in a fixed-dose regimen in women undergoing ovarian stimulation.

A prospective, randomized, open, multicentre (n = 3) study was conducted to compare the efficacy and efficiency of a fixed daily dose of 150 IU (3x50 IU) recombinant follicle stimulating hormone (recFSH, Puregon((R))) and 225 IU (3x75 IU) highly purified urinary FSH (uFSH-HP, Metrodin-HP((R))) in women undergoing ovarian stimulation prior to in-vitro fertilization treatment. A total of 165 women were treated with FSH, 83 subjects with recFSH and 82 subjects with uFSH-HP. In the recFSH group a mean number of 8.8 oocytes were retrieved, compared with 9.8 in the uFSH-HP group (not statistically significant). In the recFSH group, a significantly lower total dose was required compared to the uFSH-HP group, 1479 versus 2139 IU, respectively (P < 0.0001; 95% confidence interval -747 to -572). Treatment with recFSH resulted in a significantly higher embryo development rate (69.6 versus 56.2%; P = 0.003) and more embryos accessible for the embryo freezing programme (3.3 versus 2.0; P = 0.02) compared to uFSH-HP. The vital pregnancy rate per cycle started was 30.2 versus 28.3% in the recombinant and urinary FSH group, respectively. It is concluded that treatment outcome of a fixed daily dose of 150 IU recFSH is comparable to a fixed daily dose of 225 IU uFSH-HP. However, a significantly lower total dose was needed in the recFSH group (nearly 700 IU less).

A comparison of in vitro fertilization results after embryo transfer after 2, 3, and 4 days of embryo culture.

Embryo transfer results after a 2 to 4 day period of embryo culture were compared. Two thousand two hundred ninety-seven ETs, performed in 1991 and 1992, were analyzed. Ongoing pregnancy rates after 2, 3, or 4 days of embryo culture were 23.3%, 21.9%, and 26.4%, respectively. Multiple pregnancy rates were 36.2%, 38.8%, and 32.6% per ongoing pregnancy for the three groups, respectively. The implantation rate of 73 cavitating morulae on day 4 was surprisingly high (41%) compared with that of other developmental stages. Transfer after 4 days of culture gives the ability to recognize embryos with a very high implantation potential.

Doubling the human menopausal gonadotrophin dose in the course of an in-vitro fertilization treatment cycle in low responders: a randomized study.

The effect of doubling the human menopausal gonadotrophin (HMG) dose in the same treatment cycle in which the ovarian response after 5 days of ovarian stimulation with 225 IU/day is 'low', has been evaluated in a prospective randomized study. Forty-six patients met the ultrasound and oestradiol criteria for enrollment in the study, one patient participated twice. In 22 patients treatment was continued with 225 IU HMG/day and in 25 patients the HMG dose was increased to 450 IU/day. No effect of doubling the HMG dose was found on the length of the ovarian stimulation, peak oestradiol values, number of follicles > or = 11 and > or = 14 mm in diameter respectively on ultrasound on the day of HCG administration, number of cancelled cycles, number of oocytes at follicular puncture and the number of patients with < or = 3 oocytes at retrieval. It is concluded that doubling the HMG dose in the course of an IVF treatment cycle is not effective in enhancing ovarian response in low responders. This is in accordance with current theories on follicular growth, which state that follicular recruitment occurs only in the late luteal and early follicular phase of the menstrual cycle.

Comparison of results obtained with human serum and a protein solution as a supplement for in vitro fertilization culture medium.

A prospective controlled study was performed to compare the PRs obtained after use of a uniform IVF culture medium containing a pasteurized serum protein solution or patient serum. The ongoing PRs per ET in the serum and the protein solution group were 32% and 28%, respectively (not significant). Culture of supernumerary embryos showed blastocyst formation and even hatching with both supplements. The PR will not drop when this protein solution is used as a protein supplement in IVF culture medium instead of patient serum.

17 beta-Oestradiol, androstenedione and inhibin levels in fluid from individual follicles of normal and polycystic ovaries, and in ovaries from androgen treated female to male transsexuals.

OBJECTIVE: The aim was to monitor carefully follicular growth arrest in polycystic ovaries by assay of hormones in individual follicles. DESIGN AND PATIENTS: Fluid from follicles less than or equal to 10 mm was obtained from ovaries of 16 regularly cycling women between days 1 and 12 of the follicular phase (controls, n = 120 follicles), polycystic ovaries of five women with polycystic ovary syndrome (n = 43), and polycystic ovaries from 14 long-term testosterone treated female to male transsexuals (n = 120). MEASUREMENTS: Fluid was assayed for oestradiol, androstenedione, and immunoactive inhibin. Luteinizing hormone, follicle-stimulating hormone, and testosterone levels were estimated in serum. RESULTS: Median serum LH was lower in transsexuals than in controls (P less than 0.05), and in polycystic ovary syndrome (P less than 0.01). Median serum testosterone was not significantly different between polycystic ovary syndrome and transsexuals, and was elevated in both groups as compared to controls (P less than 0.01). Oestradiol was present in all follicles obtained from polycystic ovaries of polycystic and transsexual patients, in which no follicle greater than 10 mm could be detected. In the three groups, between-patient differences in mean oestradiol, androstenedione, inhibin, and androstenedione/oestradiol ratio were significantly larger than expected in view of the variation between follicles within individuals. Taking into account this between-patient difference, no significant differences could be established between the three groups for all endocrine parameters. The percentage of presumed healthy follicles (androstenedione/oestradiol ratio less than or equal to 4) was 12% in controls, 17% in polycystics, and 14% in transsexuals, and was not significantly different between groups. CONCLUSIONS: The results may indicate that (1) abnormally high circulating androgen concentrations with or without elevated LH levels disturb the process of selection, and could therefore play a role in the pathogenesis of polycystic ovaries; (2) in polycystic ovaries from polycystic ovary syndrome and transsexual patients, aromatase activity is present in vivo in small antral follicles, and the proportion of presumed healthy follicles is not different from that encountered in normal ovaries; (3) oestradiol levels are not different between non-dominant follicles of normal and polycystic ovaries, suggesting that only enhancement of aromatase activity by FSH may be disrupted in polycystic ovaries, (4) because androstenedione levels are not different comparing follicles of normal and polycystic ovaries, hyperandrogenaemia in the syndrome seems to originate from the abnormally high number of cystic atretic follicles generally observed in polycystic ovaries; (5) marked variation in the endocrine follicular microenvironment within and between-women precludes pooling fluid from several follicles.

Vaginal disinfection with povidon iodine and the outcome of in-vitro fertilization.

In a prospective randomized study, the influence was assessed of vaginal disinfection with a 1% solution of povidon iodine (Betadine), before performing a transvaginal ultrasound-guided oocyte retrieval, on fertilization, cleavage rate and pregnancy rate. The outcome of 334 oocyte retrievals was studied. In 160 cases, Betadine was used and in the remaining 174 cases, normal saline was used. No differences in the fertilization and cleavage rates were found (fertilization 45.5% versus 47.8%, cleavage 49.8% versus 52.1% in the Betadine and normal saline groups respectively). However the pregnancy rate was significantly higher in the normal saline group (17.2% versus 30.3% clinical pregnancies per embryo transfer). No increase in infection risk occurred in the saline group.

Results of IVF from a prospective multicentre study.

Part of a cost-effectiveness study of in-vitro fertilization was the evaluation of the medical results of this fertility treatment. Data were prospectively collected from greater than 3000 IVF treatments in five Dutch hospitals during a 2-year period. The average 'take-at-least-one-healthy-baby-home-rate' per started treatment was 10% (the average clinical pregnancy rate per embryo transfer was 20%). After more IVF treatments, about one in three to four couples were successful. Differences in results were mainly caused by patient characteristics, the treatment episode and the treating hospital. These differences remained in a multivariate logistic regression analysis.

Accuracy and safety of transvaginal sonographic placental localization.

Transvaginal sonographic localization of the placenta was performed in 100 patients suspected of having placenta previa. Except in one patient, the diagnosis was confirmed at cesarean delivery in all cases of placenta previa found by sonography before delivery, resulting in a 93.3% predictive value of a positive test. The predictive value of a negative test was 97.6%; in two patients a low-insertion placenta diagnosed by sonography was found to be a placenta previa at delivery. The sensitivity and specificity of the technique were 87.5 and 98.8%, respectively. Although in some instances transvaginal sonography was performed during vaginal hemorrhage, aggravation of bleeding was never observed. Transvaginal sonographic localization of the placenta proved to be an accurate and safe diagnostic procedure.

[The results of in-vitro fertilization in a Dutch multicenter study]. / De resultaten van in vitro-fertilisatie in een Nederlands multicentrisch onderzoek.

Part of a cost-effectiveness study on in-vitro fertilisation was the evaluation of the medical results of this fertility treatment. Data were prospectively collected from more than 3000 IVF treatments in the five Dutch hospitals during a two-year period. The average take-at-least-one-healthy-baby-home rate per started treatment was 10% (the average clinical pregnancy rate per embryo transfer was 20%). After several IVF treatments about one in three or four couples were successful. Ranges in results were mainly caused by patient characteristics, the individual treatment number and the treating hospital. Male subfertility and long-lasting and primary infertility result in a bad prognosis. Success rates differed substantially between hospitals, even after correction for patient mix.

The influence of the interval between in vitro fertilization and embryo transfer and some other variables on treatment outcome.

This prospectively randomized study compares the outcome of 434 ETs 48 to 52 hours after insemination (day 2) and 324 ETs 72 to 76 hours after insemination (day 3). The influence of the interval between insemination and ET was assessed, as well as that of the number of embryos transferred, embryo quality, and the presence of supernumerary embryos. The mean number of embryos transferred after 2 and 3 days was equal (2.9 embryos/ET). The pregnancy rates per ET were not significantly different (21.9% versus 23.5%), but a higher percentage of viable pregnancies was observed after ET on day 3 (88.2% against 69.5% following ET on day 2). Treatment outcome was positively correlated with the number of embryos transferred and the presence of supernumerary embryos.

The value and role of plasma 17 beta-oestradiol measurements during ovarian hyperstimulation for in-vitro fertilization.

Follicular aspiration was performed in 464 hyperstimulated IVF treatment cycles in patients with severe tubal damage as the sole cause of their infertility. In 413 cycles, one to four embryos could be replaced, resulting in 102 clinical pregnancies. In 458 treatment cycles, data on plasma E2 levels were available on days -3 and -2, in 322 cycles also on days -1 and 0, day 0 being the day of follicular puncture. Although the distribution of cycles leading to clinical pregnancy within the 5-95th centile for plasma E2 levels differed from that observed outside this range, these differences were of no statistical significance. These results indicate that IVF pregnancies occur in the presence of a wide range of E2 levels, during the 3-day period preceding follicular aspiration. The importance of plasma E2 measurements for treatment policy must, therefore, be reconsidered.

Factors influencing the outcome of successive IVF treatment cycles in attaining a follicular puncture.

An analysis has been made on data from 576 cycles in 300 patients regarding the chances of various superovulation protocols attaining a puncture in successive cycles. The cumulative proportion of patients with at least one successful stimulation increased from 77% at the first attempt, to 98% at the fifth attempt. Of the 576 stimulations, 440 (76%) resulted in a puncture. Age, the number of ovaries and the reaction to superovulation induction contribute to the outcome of a cycle, the chances being lowest for older individuals with one ovary and an inadequate reaction in the first treatment cycle. Changing the treatment protocol did not improve the outcome in subsequent gonadotrophin-induced cycles, even if combined with clomiphene citrate. Reasons for cancellation did not tend to recur, although the incidence of dominance and premature stimulation was significantly higher in patients aged greater than 35 years. Age-dependent chances of success were calculated.

Ultrasonically guided percutaneous and transvaginal follicle aspiration; a comparative study.

In this study we compare the efficacy of ultrasonically guided percutaneous oocyte collection for in-vitro fertilization with ultrasonically guided transvaginal oocyte collection. Forty-seven patients were prospectively randomized into two groups. Twenty-four patients underwent percutaneous follicle aspiration and 23 patients underwent a transvaginal puncture. The number of aspirated oocytes per patient showed a statistically significant difference in the two groups: 2.5 for the percutaneous puncture versus 5.2 for the transvaginal procedure. The number of embryos per patient was 2.7 in the transvaginal puncture group versus 1.6 in the percutaneous puncture group. This difference was not statistically significant. The clinical pregnancy rate per patient was 12.5% with the percutaneous approach and 30.4% with the transvaginal technique. This difference was also not statistically significant. Since the transvaginal procedure also creates less discomfort to the patient and is less time-consuming it is concluded that this approach is preferable to the percutaneous puncture technique in obtaining oocytes for in-vitro fertilization.

Monitoring of clomiphene citrate stimulation by means of plasma 17 beta-oestradiol determinations and ultrasonographic follicle measurements in in-vitro fertilization treatment cycles.

In 57 in-vitro fertilization (IVF) cycles stimulated with clomiphene citrate the relationship between plasma 17 beta-oestradiol (E2) and ultrasonographic measurements of follicle diameter was assessed. Under both monofollicular and multifollicular conditions a wide range in plasma E2 values was observed in the late follicular phase. No significant correlation could be established between the dimensions of the dominant preovulatory follicle and plasma E2 values, in mono-follicular or multi-follicular cycles. Pregnancies and conceptions occurred in cycles with both low and high circulating E2 levels. In pregnancy cycles a slight increase in plasma E2 values was found on the day following administration of human chorionic gonadotrophin (HCG). In conceptional cycles not leading to a clinical pregnancy, plasma E2 profiles varied considerably, whereas in cycles in which no oocytes were fertilized, plateauing or a distinct decrease occurred during this particular period. The present study suggests that the relative daily increase in plasma E2 values may be the most relevant aspect of plasma E2 monitoring.

24-h echographic profile study on follicular growth prior to laparoscopic aspiration of the graafian follicle in clomiphene citrate/human chorionic gonadotrophin-stimulated cycles.

Follicular growth in the last 24 h preceding laparoscopic oocyte pick-up for in vitro fertilization purposes was studied in 46 clomiphene citrate/human chorionic gonadotrophin-stimulated cycles by means of real-time sector ultrasound. A linear increase in mean follicular diameter of 2.5 mm was established. Growth rates under monofollicular and multifollicular conditions did not differ significantly. However, the absolute dimensions of the dominant follicle in the multifollicular subgroup exceeded those observed in the monofollicular subgroup (P less than 0.01) for each observation point. A fixed CC/hCG treatment scheme results in a wide range of ultimate preovulatory follicular dimensions, without any correlation between the individual follicular size and growth rate values (r = 0.075).

Ultrasonographic assessment of Graafian follicle growth under monofollicular and multifollicular conditions in clomiphene citrate-stimulated cycles.

Growth of the dominant follicle was assessed by means of real-time sector scanning in 52 clomiphene citrate-stimulated cycles in 44 patients awaiting laparoscopic oocyte recovery for in vitro fertilization purposes. Follicular growth profiles under both monofollicular and multifollicular conditions were compared with each other and with a reference growth curve derived from 26 ovulatory cycles in 25 spontaneously cycling women. In the clomiphene-stimulated cycles, growth of the dominant follicle under both monofollicular and multifollicular conditions was significantly faster (P less than 0.01) than in the reference group. There was no significant difference in follicular growth between monofollicular and multifollicular clomiphene-stimulated cycles.