Human Reproduction vol.6 no.6 pp.805-810. 1991
Results of FVF from a prospective multicentre study
G.Haan'-7, R.E.Bernardus 2 , J.M.G.Hollanders 3 , R.A.Leerentveld4, F.M.Prak 5 and N.Naaktgeboren6 'Institute for Medical Technology Assessment, University of Limburg, PO Box 616, 6200 MD Maastricht, 2Free University Hospital, Amsterdam (now Regional Hospital Gooi-Noord, Bussum), 3St Radboud University Hospital, Nijmegen 4Academic Hospital Dijkzigt, Rotterdam, 5St Elisabeth Hospital, Tilburg and 'Academic Hospital, Leiden, The Netherlands 7
To whom correspondence should be addressed at: Joh. v.d. Waalslaan 5, 5056 VH Berkel-Enschot, The Netherlands
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 >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 FVF 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. Key words: infertility/IVF/pregnancy rates/prognostic factors/ multivariate analysis
Introduction The medical results of in-vitro fertilization (IVF) were prospectively analysed as part of a technology assessment in the Netherlands (see Haan et al., 1990). The technology assessment was an initiative of the advisory board of the social insurers, who cover >60% of the Dutch population. Based on this study this advisory board, the Health Insurance Executive Board, planned to advise the Ministry of Health with regard to reimbursement decisions of IVF. In this article only the medical part of the study will be presented.
Materials and methods Medical data from all regular IVF treatments in five Dutch IVF centres were prospectively collected in a uniform way during a period set in advance, August 1986 to June 1988. The following five hospitals were involved; Dijkzigt Hospital Rotterdam, Free University Hospital Amsterdam, University Hospital Leiden, St Radboud Hospital Nijmegen and St Elisabeth Hospital Tilburg. All were university-based centres except for the last mentioned. To ensure that all cases were included in the data set, weekly © Oxford University Press
telephone surveillances were held by the research team with every participating centre. As soon as the first clomiphene citrate (CC), human menopausal gonadotrophin (HMG) or follicle stimulating hormone (FSH) treatment was given as stimulation for IVF, the treatment was included in the database. Three thousand and ninety two successive IVF treatments were carried out on 1462 couples. A clinical pregnancy was defined as a positive urinary pregnancy test and no menstrual bleeding within 26 days after embryo transfer, and on-going pregnancy as a clinical pregnancy with fetal heart action at ultrasound, lasting for at least 12 weeks after embryo transfer (Jones et al., 1983). If success rates or results are mentioned without further comment, these represent the on-going pregnancy rates per started IVF treatment. The ultimate chance for a baby born after several IVF cycles might be more informative to parents than the on-going pregnancy rate per started cycle. Therefore the IVF success rate in the longer run was analysed in two ways: firstly, by calculating a cumulative pregnancy rate after several IVF treatment episodes, and secondly, by looking at the results for a cohort of IVF couples. The couples that were treated with IVF at least once within the first half of the study period (August 1986 to July 1987) were selected as the cohort to be followed (n = 852). These couples were followed with regard to IVF treatment results for at least 1 year, with a maximum follow-up of 2 years. Two-sided chi-square tests with a probability of 0.05 were used to test the significance of differences in results. In the multivariate logistic regression analysis, using BMDP (Engelman, 1985), 95% reliability intervals were used. Results Univariate analyses Overall results per treatment cycle. The overall results of the 3093 treatments are presented in Figure 1. About one-third of the started treatments were not continued as far as embryo transfer. The clinical pregnancy rate per embryo transfer was 20% and only 13.5% per started cycle. Of these clinical pregnancies, one-fifth ended in an abortion or an ectopic pregnancy (n = 93). The on-going pregnancy rate per started IVF treatment was 10%, of which 10 (3%) ended in a late abortion (gestational age between 12 and 28 weeks). Of the on-going pregnancies resulting in at least one liveborn baby, one-quarter (n = 84) were multiple with 14 triplets and 2 quadruplets. The rate of multiple pregnancy per on-going pregnancy was significantly related to the number of embryos transferred: - 2 0 % for 2 to 3 embryos transferred (n = 132 on-going pregnancies), - 3 5 % for 4 to 5 embryos transferred 805
results of IVF treatments (% of started treatments)
Table I. Pregnancy results in a cohort approach Total number of couples Couples with at least 1 follicle aspiration Couples with at least 1 embryo transfer Couples with at least 1 clinical pregnancy
852 800 715 253 (29.7% of all couples) 203 (23.8% of all couples) 2.5 2.0 1.6 13 1
Couples with at least 1 on-going pregnancy Mean number of started treatments per couple Mean number of follicle aspirations per couple Mean number of embryo transfers per couple Couples with a clinical pregnancy twice Couples with an on-going pregnancy twice
% on-going pregnancy per started treatment
1 3.4%
1 1.4%
stimulation '"=3092)
follicleaspiration (n=2466)
on—going pregnancy
(n=323)
Fig. 1. Results of subsequent phases in the IVF treatment.
(« = 137 on-going pregnancies) and 46% for 6 or more embryos transferred (n = 28 on-going pregnancies). Of 393 children for whom obstetrical data were available, 38% had a low birth weight ( < 2500 g) and 7 % had a very low birth weight ( < 1500 g). This last figure can be differentiated into 1.8% for single pregnancies and 12.8% for multiple pregnancies. The date of delivery was pre-term ( < 3 7 weeks) in 30% of the IVF deliveries (15% for singletons and 65% for multiples); it was very-pre-term ( < 3 2 weeks) in 5% of deliveries (2.5% for singletons and 11 % for multiples). The overall Caesarian section rate was 27%, for the multiple pregnancies it was 48%. Seven neonatal deaths occurred (1.8%). All but one of the deaths were from multiple pregnancies (with at least one baby still alive). Of six children with congenital abnormalities, four died within 28 days after delivery: two anencephalus, one vitium cordis, one other chromosomal and congenital abnormality, one intestinum atresia (alive) and one pes equinovarus (alive). Four of these children (except one anencephalus and pes equinovarus) were from multiple pregnancies. Cumulative pregnancy rates and cohort approach. First, the results were analysed for each episode of IVF treatment. A slight decline was seen: 12.2% at the first treatment, 10.4% at the second and third treatments and 6.8% after further treatment episodes (P < 0.05). For further details on the cumulative success rates, see Haan etal. (1991). The results of the follow-up of 852 couples in the cohort approach are presented in Table I. Almost one in four couples achieved an on-going pregnancy, with a mean of 2.5 started IVF treatments or two follicle aspirations. Results related to patients' characteristics and treatment centres. So far, only the mean IVF results have been described. However, in the analyses, huge differences in results appeared to be present which can ultimately be classified into two groups: differences 806
306
only ti_toal tubal factor in male combination subfertility factor
tubal factor and male subfertility
n-157
endometriosis
infertility unexplained
Fig. 2. Pregnancy rates in relation to aetiological factors.
between patient groups according to patient characteristics and differences between treatment centres. Patient characteristics. Tubal pathology was present in 90% of all studied cycles. In almost 75%, the tubal factor (excluding patients after tubal sterilization) was the sole indication present. The on-going pregnancy rates per started treatment for several indications are presented in Figure 2, with an overlap in the case of multiple indications. Significantly better results (P < 0.05) were obtained in the tubal group in comparison to all other categories. In addition, 70% of the couples with solely a tubal factor, had a history of one or more tubal surgeries. No differences were observed in the outcome of IVF between the operated and non-operated tubal patients. In cases where a tubal factor was associated with other factors, the favourable prognosis disappeared, especially when a male factor was present. In the group with male subfertility, significantly worse results were obtained (P < 0.01). Idiopathic infertility as a whole (n = 157)
IVF results of a prospective multicentre study
13.6%
% on-going pregnancy per started treatment
% on-going pregnancy per started treatment 15.2%
1 1.3%
12.7%
n=632
n=1342
n=1009
n=1O3
n= 835
n= n= 592 1643
35 - 39 year
> 40 year
n= n= 173 361 primary infertility
4 - 5 years
3 years
30 - 34 year
n= 571
n= n= n= 264 419 1282 secondary Infertility
> 6 years
Fig. 4. Pregnancy rates in relation to duration of infertility.
Fig. 3. Pregnancy rates in relation to women's age. % on-going pregnancy had a favourable prognosis: 13.4% on-going pregnancy rate per started cycle. However, when this group was divided according to the duration of infertility > 6 (n = 115) and < 6 years (« = 42), the on-going pregnancy rates were significantly different (P < 0.01): 8.7% and 26.2% respectively. When only one ovary was present, the on-going pregnancy rate per started IVF treatment was significantly reduced: 7.7% versus 11.2% (P < 0.05), which was a consequence of poorer results in all phases of the IVF treatment. The results related to women's age showed a significant (P < 0.01) decline (Figure 3). This same decline appeared in the group with purely tubal pathology. A real breakpoint could not be found; it was more like a gradual slope. The duration of infertility can be regarded as an indicator for the unobservable variable 'severity of the fertility problems'. A significant (P < 0.01) decline in on-going pregnancy was observed as the duration of infertility increased (Figure 4). This trend was present in all phases of the IVF treatment. A critical 'breakpoint' seems to emerge earlier in primary infertile women ( ~ 3 years) in comparison to secondary infertile women ( ~ 5 years). The influence of an earlier pregnancy on the IVF results was very illustrative of the fact that (sub)fertility is principally the outcome of the interaction between two particular partners (Figure 5): the IVF results for women with an earlier pregnancy in another previous relationship were similar to those of women with primary infertility and were significantly reduced in comparison to the results in couples with an earlier pregnancy within the existing relationship (P < 0.05).
1 2.6%
n=1105
secondary infertility female and couple
n=325
secondary infertility female, primary infertility couple
n=1662
primary infertility
Fig. 5. Pregnancy rates in relation to previous pregnancies. Treatment centres. The average on-going pregnancy rate per started IVF treatment was almost three times higher in the centre with the best results in comparison to the centre with the worst 807
G.Haan el al.
Table II. Estimations for the logistic regression model with on-going pregnancy as dependent variable; explanatory variables : patient characteristics and treatment episode number Odds ratio
Table HI. Estimations for the logistic regression model with on-going pregnancy as dependent variable; explanatory variables; IVF centres, patient characteristics and treatment episode number
Reliability interval
Male factor 0.31-0.72 0.48 Idiopathic infertility 1.54 1.02-2.32 One ovary 0.65 0.50-0.85 Woman > 36 years 0.45-0.75 0.58 Duration of infertility 0.64 0.52-0.79 Treatment episode 0.86 0.77-0.95 Constant factor 0.23 0.19-0.29 % on-going pregnancy per started cycle: 18.82% (15. 61-22.50) in the base category
Male factor Idiopathic infertility One ovary Woman > 36 years Duration of infertility Treatment episode Clinic 1 Clinic 2 Clinic 3
Odds ratio
Reliability interval
0.49 1.50 0.65 0.56 0.64 0.86
0.33-0.75 0.99-2.27 0.49-0.85 0.43-0.72 0.52-0.79 0.78-0.96
% on-going pregnancy (reliability interval)
16.65% (12.82-21.33%) 17.05% (12.82-22.31%) 9.78% (6.87-13.74%)
Clinic 4 Clinic 5
results (14.5 versus 5.2%). The differences in results could be explained only in a very limited way by differences in treatment modalities between the centres which, according to the literature, may have influenced the outcome. Differences were observed with regard to e.g. the medication in the follicular and luteal phases, different time intervals between several treatment activities, the oestradiol patterns and the method of follicle aspiration (Haan, 1989). Multivariate analyses Because the patient mix was somewhat different between the participating centres (e.g. proportions in aetiological categories, age distribution, primary or secondary infertility), it was interesting to see whether the differences from the univariate analyses would remain valid for the multivariate analyses. First of all, a regression model was built with different patient characteristics and the treatment episode number as explanatory variables. The dependent variable was the dummy on-going pregnancy, which took value 1 if the started IVF cycle resulted in an on-going pregnancy and value 0 if the treatment was unsuccessful. All the explanatory variables related to patient characteristics are defined as dummy variables, being either 1 (if present) or 0 (if absent). The variable infertility period has value 1 if it was primary infertility for at least 5 years, otherwise (primary infertility < 5 years or secondary infertility) it has value 0. The explanatory variable treatment episode has four categories, numbered from 1 to 4, where the last category includes the treatment episodes > 4 . The odds ratios for this variable are relative to the former category. The model calculates estimates for the odds ratios from the data. Odds ratios can more or less be interpreted as relative risk ratios (for fertility treatments a more suitable term might be the relative chance ratio), see for instance Kleinbaum et al. (1982). An odds ratio of 1 means that the odds (read: chance) within this group for an on-going pregnancy is the same as in the comparative group. If a 95% reliability interval excludes the value 1, the explanatory variable can be interpreted as being significantly important. From the odds for the constant factor, the base level of the chance of pregnancy was calculated to be 18.8% (Table II). This percentage is valid for the patients with a base score on every explanatory variable included in the analysis, for instance no male subfertility, women's age
Results of FVF from a prospective multicentre study
G.Haan'-7, R.E.Bernardus 2 , J.M.G.Hollanders 3 , R.A.Leerentveld4, F.M.Prak 5 and N.Naaktgeboren6 'Institute for Medical Technology Assessment, University of Limburg, PO Box 616, 6200 MD Maastricht, 2Free University Hospital, Amsterdam (now Regional Hospital Gooi-Noord, Bussum), 3St Radboud University Hospital, Nijmegen 4Academic Hospital Dijkzigt, Rotterdam, 5St Elisabeth Hospital, Tilburg and 'Academic Hospital, Leiden, The Netherlands 7
To whom correspondence should be addressed at: Joh. v.d. Waalslaan 5, 5056 VH Berkel-Enschot, The Netherlands
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 >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 FVF 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. Key words: infertility/IVF/pregnancy rates/prognostic factors/ multivariate analysis
Introduction The medical results of in-vitro fertilization (IVF) were prospectively analysed as part of a technology assessment in the Netherlands (see Haan et al., 1990). The technology assessment was an initiative of the advisory board of the social insurers, who cover >60% of the Dutch population. Based on this study this advisory board, the Health Insurance Executive Board, planned to advise the Ministry of Health with regard to reimbursement decisions of IVF. In this article only the medical part of the study will be presented.
Materials and methods Medical data from all regular IVF treatments in five Dutch IVF centres were prospectively collected in a uniform way during a period set in advance, August 1986 to June 1988. The following five hospitals were involved; Dijkzigt Hospital Rotterdam, Free University Hospital Amsterdam, University Hospital Leiden, St Radboud Hospital Nijmegen and St Elisabeth Hospital Tilburg. All were university-based centres except for the last mentioned. To ensure that all cases were included in the data set, weekly © Oxford University Press
telephone surveillances were held by the research team with every participating centre. As soon as the first clomiphene citrate (CC), human menopausal gonadotrophin (HMG) or follicle stimulating hormone (FSH) treatment was given as stimulation for IVF, the treatment was included in the database. Three thousand and ninety two successive IVF treatments were carried out on 1462 couples. A clinical pregnancy was defined as a positive urinary pregnancy test and no menstrual bleeding within 26 days after embryo transfer, and on-going pregnancy as a clinical pregnancy with fetal heart action at ultrasound, lasting for at least 12 weeks after embryo transfer (Jones et al., 1983). If success rates or results are mentioned without further comment, these represent the on-going pregnancy rates per started IVF treatment. The ultimate chance for a baby born after several IVF cycles might be more informative to parents than the on-going pregnancy rate per started cycle. Therefore the IVF success rate in the longer run was analysed in two ways: firstly, by calculating a cumulative pregnancy rate after several IVF treatment episodes, and secondly, by looking at the results for a cohort of IVF couples. The couples that were treated with IVF at least once within the first half of the study period (August 1986 to July 1987) were selected as the cohort to be followed (n = 852). These couples were followed with regard to IVF treatment results for at least 1 year, with a maximum follow-up of 2 years. Two-sided chi-square tests with a probability of 0.05 were used to test the significance of differences in results. In the multivariate logistic regression analysis, using BMDP (Engelman, 1985), 95% reliability intervals were used. Results Univariate analyses Overall results per treatment cycle. The overall results of the 3093 treatments are presented in Figure 1. About one-third of the started treatments were not continued as far as embryo transfer. The clinical pregnancy rate per embryo transfer was 20% and only 13.5% per started cycle. Of these clinical pregnancies, one-fifth ended in an abortion or an ectopic pregnancy (n = 93). The on-going pregnancy rate per started IVF treatment was 10%, of which 10 (3%) ended in a late abortion (gestational age between 12 and 28 weeks). Of the on-going pregnancies resulting in at least one liveborn baby, one-quarter (n = 84) were multiple with 14 triplets and 2 quadruplets. The rate of multiple pregnancy per on-going pregnancy was significantly related to the number of embryos transferred: - 2 0 % for 2 to 3 embryos transferred (n = 132 on-going pregnancies), - 3 5 % for 4 to 5 embryos transferred 805
results of IVF treatments (% of started treatments)
Table I. Pregnancy results in a cohort approach Total number of couples Couples with at least 1 follicle aspiration Couples with at least 1 embryo transfer Couples with at least 1 clinical pregnancy
852 800 715 253 (29.7% of all couples) 203 (23.8% of all couples) 2.5 2.0 1.6 13 1
Couples with at least 1 on-going pregnancy Mean number of started treatments per couple Mean number of follicle aspirations per couple Mean number of embryo transfers per couple Couples with a clinical pregnancy twice Couples with an on-going pregnancy twice
% on-going pregnancy per started treatment
1 3.4%
1 1.4%
stimulation '"=3092)
follicleaspiration (n=2466)
on—going pregnancy
(n=323)
Fig. 1. Results of subsequent phases in the IVF treatment.
(« = 137 on-going pregnancies) and 46% for 6 or more embryos transferred (n = 28 on-going pregnancies). Of 393 children for whom obstetrical data were available, 38% had a low birth weight ( < 2500 g) and 7 % had a very low birth weight ( < 1500 g). This last figure can be differentiated into 1.8% for single pregnancies and 12.8% for multiple pregnancies. The date of delivery was pre-term ( < 3 7 weeks) in 30% of the IVF deliveries (15% for singletons and 65% for multiples); it was very-pre-term ( < 3 2 weeks) in 5% of deliveries (2.5% for singletons and 11 % for multiples). The overall Caesarian section rate was 27%, for the multiple pregnancies it was 48%. Seven neonatal deaths occurred (1.8%). All but one of the deaths were from multiple pregnancies (with at least one baby still alive). Of six children with congenital abnormalities, four died within 28 days after delivery: two anencephalus, one vitium cordis, one other chromosomal and congenital abnormality, one intestinum atresia (alive) and one pes equinovarus (alive). Four of these children (except one anencephalus and pes equinovarus) were from multiple pregnancies. Cumulative pregnancy rates and cohort approach. First, the results were analysed for each episode of IVF treatment. A slight decline was seen: 12.2% at the first treatment, 10.4% at the second and third treatments and 6.8% after further treatment episodes (P < 0.05). For further details on the cumulative success rates, see Haan etal. (1991). The results of the follow-up of 852 couples in the cohort approach are presented in Table I. Almost one in four couples achieved an on-going pregnancy, with a mean of 2.5 started IVF treatments or two follicle aspirations. Results related to patients' characteristics and treatment centres. So far, only the mean IVF results have been described. However, in the analyses, huge differences in results appeared to be present which can ultimately be classified into two groups: differences 806
306
only ti_toal tubal factor in male combination subfertility factor
tubal factor and male subfertility
n-157
endometriosis
infertility unexplained
Fig. 2. Pregnancy rates in relation to aetiological factors.
between patient groups according to patient characteristics and differences between treatment centres. Patient characteristics. Tubal pathology was present in 90% of all studied cycles. In almost 75%, the tubal factor (excluding patients after tubal sterilization) was the sole indication present. The on-going pregnancy rates per started treatment for several indications are presented in Figure 2, with an overlap in the case of multiple indications. Significantly better results (P < 0.05) were obtained in the tubal group in comparison to all other categories. In addition, 70% of the couples with solely a tubal factor, had a history of one or more tubal surgeries. No differences were observed in the outcome of IVF between the operated and non-operated tubal patients. In cases where a tubal factor was associated with other factors, the favourable prognosis disappeared, especially when a male factor was present. In the group with male subfertility, significantly worse results were obtained (P < 0.01). Idiopathic infertility as a whole (n = 157)
IVF results of a prospective multicentre study
13.6%
% on-going pregnancy per started treatment
% on-going pregnancy per started treatment 15.2%
1 1.3%
12.7%
n=632
n=1342
n=1009
n=1O3
n= 835
n= n= 592 1643
35 - 39 year
> 40 year
n= n= 173 361 primary infertility
4 - 5 years
3 years
30 - 34 year
n= 571
n= n= n= 264 419 1282 secondary Infertility
> 6 years
Fig. 4. Pregnancy rates in relation to duration of infertility.
Fig. 3. Pregnancy rates in relation to women's age. % on-going pregnancy had a favourable prognosis: 13.4% on-going pregnancy rate per started cycle. However, when this group was divided according to the duration of infertility > 6 (n = 115) and < 6 years (« = 42), the on-going pregnancy rates were significantly different (P < 0.01): 8.7% and 26.2% respectively. When only one ovary was present, the on-going pregnancy rate per started IVF treatment was significantly reduced: 7.7% versus 11.2% (P < 0.05), which was a consequence of poorer results in all phases of the IVF treatment. The results related to women's age showed a significant (P < 0.01) decline (Figure 3). This same decline appeared in the group with purely tubal pathology. A real breakpoint could not be found; it was more like a gradual slope. The duration of infertility can be regarded as an indicator for the unobservable variable 'severity of the fertility problems'. A significant (P < 0.01) decline in on-going pregnancy was observed as the duration of infertility increased (Figure 4). This trend was present in all phases of the IVF treatment. A critical 'breakpoint' seems to emerge earlier in primary infertile women ( ~ 3 years) in comparison to secondary infertile women ( ~ 5 years). The influence of an earlier pregnancy on the IVF results was very illustrative of the fact that (sub)fertility is principally the outcome of the interaction between two particular partners (Figure 5): the IVF results for women with an earlier pregnancy in another previous relationship were similar to those of women with primary infertility and were significantly reduced in comparison to the results in couples with an earlier pregnancy within the existing relationship (P < 0.05).
1 2.6%
n=1105
secondary infertility female and couple
n=325
secondary infertility female, primary infertility couple
n=1662
primary infertility
Fig. 5. Pregnancy rates in relation to previous pregnancies. Treatment centres. The average on-going pregnancy rate per started IVF treatment was almost three times higher in the centre with the best results in comparison to the centre with the worst 807
G.Haan el al.
Table II. Estimations for the logistic regression model with on-going pregnancy as dependent variable; explanatory variables : patient characteristics and treatment episode number Odds ratio
Table HI. Estimations for the logistic regression model with on-going pregnancy as dependent variable; explanatory variables; IVF centres, patient characteristics and treatment episode number
Reliability interval
Male factor 0.31-0.72 0.48 Idiopathic infertility 1.54 1.02-2.32 One ovary 0.65 0.50-0.85 Woman > 36 years 0.45-0.75 0.58 Duration of infertility 0.64 0.52-0.79 Treatment episode 0.86 0.77-0.95 Constant factor 0.23 0.19-0.29 % on-going pregnancy per started cycle: 18.82% (15. 61-22.50) in the base category
Male factor Idiopathic infertility One ovary Woman > 36 years Duration of infertility Treatment episode Clinic 1 Clinic 2 Clinic 3
Odds ratio
Reliability interval
0.49 1.50 0.65 0.56 0.64 0.86
0.33-0.75 0.99-2.27 0.49-0.85 0.43-0.72 0.52-0.79 0.78-0.96
% on-going pregnancy (reliability interval)
16.65% (12.82-21.33%) 17.05% (12.82-22.31%) 9.78% (6.87-13.74%)
Clinic 4 Clinic 5
results (14.5 versus 5.2%). The differences in results could be explained only in a very limited way by differences in treatment modalities between the centres which, according to the literature, may have influenced the outcome. Differences were observed with regard to e.g. the medication in the follicular and luteal phases, different time intervals between several treatment activities, the oestradiol patterns and the method of follicle aspiration (Haan, 1989). Multivariate analyses Because the patient mix was somewhat different between the participating centres (e.g. proportions in aetiological categories, age distribution, primary or secondary infertility), it was interesting to see whether the differences from the univariate analyses would remain valid for the multivariate analyses. First of all, a regression model was built with different patient characteristics and the treatment episode number as explanatory variables. The dependent variable was the dummy on-going pregnancy, which took value 1 if the started IVF cycle resulted in an on-going pregnancy and value 0 if the treatment was unsuccessful. All the explanatory variables related to patient characteristics are defined as dummy variables, being either 1 (if present) or 0 (if absent). The variable infertility period has value 1 if it was primary infertility for at least 5 years, otherwise (primary infertility < 5 years or secondary infertility) it has value 0. The explanatory variable treatment episode has four categories, numbered from 1 to 4, where the last category includes the treatment episodes > 4 . The odds ratios for this variable are relative to the former category. The model calculates estimates for the odds ratios from the data. Odds ratios can more or less be interpreted as relative risk ratios (for fertility treatments a more suitable term might be the relative chance ratio), see for instance Kleinbaum et al. (1982). An odds ratio of 1 means that the odds (read: chance) within this group for an on-going pregnancy is the same as in the comparative group. If a 95% reliability interval excludes the value 1, the explanatory variable can be interpreted as being significantly important. From the odds for the constant factor, the base level of the chance of pregnancy was calculated to be 18.8% (Table II). This percentage is valid for the patients with a base score on every explanatory variable included in the analysis, for instance no male subfertility, women's age
