Andrology: Auto-controlled study on in-vitro fertilization performance with 'antibody-free' spermatozoa selected by immunobead adsorption from semen of patients with anti-sperm antibodies

Selection of antibody-free spermatozoa by immunobead adsorptionwas performed as a preliminary test in order to check probablerecovery before introducing the procedure in an in-vitro fertilization(IVF) trial. On this basis, only nine out of 21 couples couldbe allocated to the study on IVF, which was designed to comparefertilization rates obtained with the immuno-selected spermatozoafraction versus the control swim-up fraction. The study comprisedeight properly controlled IVF procedures with sibling oocytes.Despite the high severity of antibody-binding in the fresh semen[mean of 91% for immunoglobulin (Ig)G, 77% for IgA], selectionof antibody-free spermatozoa was successful in seven out ofeight cases (mean of 15% for IgG, 20% for IgA). Nevertheless,mean fertilization rate on a per patient basis was not differentafter using one of the two sperm preparation procedures. Fourpatients had similar fertilization rates with the two spermfractions, while for three patients fertilization was achievedonly with the immunodepleted fraction. In terms of embryo quality,similar results between the two groups were obtained. Two pregnancieswere obtained, one was obtained with swim-up-prepared spermatozoaalone; the second, a twin pregnancy, originated from both theswim-up and immunodepleted sperm populations. From this study,it can be concluded that the technique of immunobead adsorptionitself seems attractive for the selection of antibody-free spermatozoa,but can be applied only to a limited population of patients(<50%) suffering from immunological male infertility. Furthermore,in cases where immunodepletion seemed successful, no consistentbenefit was observed in terms of IVF performance. Accordingto the results of this experiment, the procedure of immunobeadadsorption is inefficient. More research is needed to elucidatewhether sperm membrane damage or selection of less functionallyactive cells by the described technique are probable causesof the failure.     

Identification of viable embryos in IVF by non-invasive measurement of amino acid turnover

BACKGROUND: IVF is limited by low success rates and an unacceptably high multiple pregnancy rate. These outcomes would be improved significantly if a single embryo of high viability could be replaced in each treatment cycle, but widespread acceptance of such a policy is hindered by the lack of predictive factors for embryo selection. We have conducted a retrospective clinical study of a novel non-invasive method of embryo selection based on the depletion/appearance of amino acids in the culture medium. METHODS: Fifty-three cycles of IVF treatment using ICSI were studied. Embryos were cultured for 24 h in 4 microl drops of medium containing a physiological mixture of 18 amino acids. The spent medium was analysed for amino acid content by high performance liquid chromatography. RESULTS: The turnover of three amino acids, Asn, Gly and Leu, was significantly correlated with a clinical pregnancy and live birth. These correlations were independent of known predictors, such as female age, basal levels of FSH, embryo cell number and embryo morphological grade. CONCLUSIONS: Non-invasive assay of amino acid turnover has the potential to improve significantly the prospective selection of the most viable embryos, or single embryo, for replacement in an IVF cycle.     

Clinical use of the perifollicular vascularity assessment in IVF cycles: a pilot study

BACKGROUND: In Italy, a recent law has imposed a ban on the fertilization of more than three oocytes at one time, and all resulting embryos produced must be transferred simultaneously. The aim of the present controlled study was to assess the clinical feasibility and efficacy of the perifollicular vascularity assessment for oocyte selection in IVF cycles. METHODS: Fifty-four young primary infertile non-obese women (27 cases and 27 age- and BMI-matched controls) underwent IVF cycles. The choice of the oocytes to fertilize was performed according to perifollicular vascularization in the experimental group, whereas in the control group, the standard morphologic criteria alone were used. The dose of gonadotrophins used, the dominant follicles obtained, the duration of the ovarian stimulation, the number of oocytes retrieved, the number/quality of oocytes fertilized and of cleaved embryos, cycle cancellation, implantation, clinical pregnancy, ongoing pregnancy, multiple pregnancies and ovarian hyperstimulation syndrome rates were assessed in each group. RESULTS: The assessment of perifollicular vascularity was feasible in 88.9% of cases. No difference between groups was detected in any parameter evaluated. CONCLUSION: Power Doppler assessment of perifollicular vascularity seems to have no clinical utility for oocyte selection in IVF cycles for young infertile women.     

Delivery rates after in-vitro fertilization following bilateral salpingectomy due to hydrosalpinges: a case control study.

This retrospective case-control study assessed the impact of bilateral salpingectomy due to uni- or bilateral hydrosalpinges on the outcome of in-vitro fertilization (IVF) in a large consecutive series of patients. The effect of bilateral salpingectomy due to hydrosalpinges on pregnancy outcome was compared in 139 patients (263 cycles) and 139 age-matched controls with tubal infertility without hydrosalpinges (296 cycles). The delivery rates per initiated cycle as well as the implantation rates were equal in the two groups (21.7 versus 21.6% and 19 versus 21%). The number of embryos, the cleavage stage, and the embryo morphology score were equal in the two groups. Among 92 patients treated with 182 IVF cycles who underwent salpingectomy between 1.5 and 5 years prior to their first IVF cycle, the delivery and the implantation rates were 22.5 and 20.5% respectively. Of the patients with salpingectomy after an average of 1.7 failed IVF cycles and who re-entered the IVF programme 3 and 6 months subsequent to surgery, 47 were treated with 83 IVF cycles. The live birth and the implantation rates after surgery in this group were 20.5 and 20% respectively. It is concluded that bilateral salpingectomy due to hydrosalpinges restores a normal delivery as well as implantation rate after IVF treatment compared to controls. A favourable outcome is also found in patients operated on after repeated IVF failures. Furthermore, a normal live birth rate as well as a high implantation rate is maintained for at least three IVF cycles subsequent to surgical treatment.     

Falling estradiol levels as a result of intentional reduction in gonadotrophin dose are not associated with poor IVF outcomes, whereas spontaneously falling estradiol levels result in low clinical pregnancy rates

BACKGROUND: Although estradiol levels remain an integral part of monitoring in most IVF programmes, the effect of falling estradiol on IVF outcome has not been adequately quantified. The objective of this study was to evaluate the effect of falling estradiol levels prior to hCG on IVF outcome. METHODS: This was a retrospective cohort study carried out in a university-based fertility clinic. A total of 112 IVF patients in whom estradiol levels fell prior to the administration of hCG were matched for age and year of treatment with 112 control IVF patients. IVF outcomes including oocytes retrieved, fertilization rate, embryos for transfer, and pregnancy rates were compared between the groups. RESULTS: Seventy per cent of women in the falling estradiol group experienced spontaneously falling estradiol levels. Spontaneously falling estradiol was associated with fewer oocytes retrieved (median 5 versus 8, P=0.001), increased rates of failed fertilization (18 versus 6%, P=0.018) and lower clinical pregnancy rates (12 versus 26%, P=0.012) compared to controls. Despite marked decreases in estradiol levels, IVF outcomes for patients whose estradiol levels fell as a result of deliberate protocol modification had similar fertilization and clinical pregnancy rates as controls. CONCLUSIONS: Subtle (<10%) spontaneous decreases in estradiol levels are associated with very poor IVF outcomes.     

The effectiveness of IVF in unexplained infertility: a systematic Cochrane review. 2002,

BACKGROUND: IVF is an accepted treatment for unexplained infertility. The objective of this review was to determine whether, for unexplained infertility, IVF improves the probability of live birth compared with: (i) expectant management; (ii) clomiphene citrate (CC); (iii) intrauterine insemination (IUI); (iv) IUI with controlled ovarian stimulation; and (v) gamete intra-Fallopian transfer (GIFT). METHODS: This was based on a Cochrane review. Randomized controlled trials (RCTs) which compared the effectiveness of IVF with expectant management, CC, IUI with or without controlled ovarian stimulation and GIFT were included. Patients included couples with unexplained infertility. Live birth rate per woman/couple was the main outcome measure. RESULTS: Nine RCT were identified. Five RCTs were included in the final meta-analysis. There were no comparative data for CC and live birth rates for expectant management or GIFT. There was no significant difference in clinical pregnancy rates between IVF and expectant management. There was no evidence of a difference in live birth rates between IVF and IUI either without (OR 1.96, 95% CI 0.88 to 4.36) or with (OR 1.15, 95% CI 0.55 to 2.42) ovarian stimulation. Clinical pregnancy rates with IVF were significantly higher compared with GIFT (OR 2.14, 95% CI 1.08 to 4.22) as were the multiple pregnancy rates (OR 6.25, 95% CI 1.70 to 23.00). Clinical heterogeneity was present among the studies. There was no evidence of statistical heterogeneity. CONCLUSIONS: The effectiveness of IVF in unexplained infertility remains unproven. Larger trials with adequate power are warranted.     

A prospective controlled study of in-vitro fertilization, gamete intra-fallopian transfer and intrauterine insemination combined with superovulation.

The relative effectiveness of in-vitro fertilization (IVF), gamete intra-Fallopian transfer (GIFT) and intrauterine insemination (IUI) combined with superovulation in the treatment of infertility were compared in 151 couples undergoing a single cycle of treatment. Treatment was selected as appropriate (IVF for tubal disease, GIFT or IUI/superovulation for nontubal infertility) but possible bias due to non-randomization was overcome by all couples having had favourable fertilization in a previous cycle of IVF. Furthermore, in a preliminary study of initial IVF treatment in 265 couples from whom the study patients were drawn, implantation and pregnancy rates in the diagnostic groups were similar. In the definitive study comparing IVF, GIFT and IUI/superovulation, the pregnancy rate observed with GIFT was highest (40%) but this was not significantly higher than with IVF (28%) or IUI/superovulation (20%). However, the implantation rate per egg transferred by GIFT (21%) was significantly higher than the implantation rate per embryo transferred by IVF (11%). Although the pregnancy rates with GIFT were not statistically greater than with IVF, a significant advantage is likely to be observed in larger groups in view of the better implantation rate. The lower pregnancy rates with IUI superovulation are to be expected because of limited ovarian stimulation, they are nevertheless of comparative interest.     

Hydrosalpinx and IVF outcome: a prospective, randomized multicentre trial in Scandinavia on salpingectomy prior to IVF.

Many retrospective studies have shown that hydrosalpinx is associated with poor in-vitro fertilization (IVF) outcome. The mechanism of the actual cause is not yet fully understood. A clinical practice of performing salpingectomy before IVF has developed, without any evidence from prospective trials. The aim of the present prospective randomized trial was to test if a salpingectomy prior to IVF was effective in terms of increased pregnancy rates. Patients with hydrosalpinx were randomized to either a laparoscopic salpingectomy or no intervention before IVF. A total of 204 patients was available for an intention-to-treat analysis and 192 actually started IVF. Clinical pregnancy rates per included patient were 36.6% in the salpingectomy group and 23.9% in the non-intervention group (not significant, P = 0.067) and the ensuing delivery rates were 28.6% and 16.3% (P = 0.045). The corresponding delivery rates per transfer cycle were 29.5% versus 17. 5% (not significant, P = 0.083). A subgroup analysis revealed significant differences in favour of salpingectomy, in implantation rates in patients with bilateral hydrosalpinges (25.6% versus 12.3%, P = 0.038) and in clinical pregnancy rates (45.7% versus 22.5%, P = 0.029) and delivery rates (40.0% versus 17.5%, P = 0.038) in patients with ultrasound visible hydrosalpinges. The delivery rate was increased 3.5-fold in patients with bilateral hydrosalpinges visible on ultrasound (P = 0.019).     

Cervical dilatation has a positive impact on the outcome of IVF in randomly assigned cases having two previous difficult embryo transfers

BACKGROUND: The difficulty of embryo transfer has been reported to affect success rates in some centres, but not in others. Cervical dilatation has been proposed as a means to overcome difficult embryo transfer, but consistent criteria for patient selection are lacking. In a prospective randomized study, we examined the influence of cervical dilatation 1-3 months before embryo transfer on the outcome of IVF in cases having difficult embryo transfer in two previously failed IVF cycles. METHODS: Two alternative methods of embryo transfer preparation were evaluated in 283 randomly assigned women having difficult embryo transfers in two previously failed IVF attempts. Randomization was made using a computer-generated random number table. Cervical dilatation before starting any IVF treatment was used in 145 cases, and no dilatation was performed in 138 cases. RESULTS: The cervical dilatation group yielded a significantly higher pregnancy rate than the non-dilated group (40% versus 24%; P < 0.01). Likewise, the implantation rate (24.1% versus 14.9%; P < 0.01) and the live birth rate (34.48% versus 19.56%; P < 0.01) were significantly higher in the dilatation group than in the non-dilated group. CONCLUSIONS: In patients with prior difficult embryo transfer, cervical dilatation 1-3 months before embryo transfer lead to an improved pregnancy rate.     

What about the remaining twins since single-embryo transfer? How far can (should) we go?

Single-embryo transfer (SET) and more specifically elective SET (eSET) have taken their place in good clinical IVF/ICSI practice. After the initial cautious search for the characteristics of the twin-prone patient and of the selection of the embryo with the highest implantation potential many centres have embarked on the (progressive) implementation of SET, either by conviction or forced by legislation or both. It was only because the ongoing pregnancy rates remained largely unaffected that SET was accepted. Generally speaking, it can be said that the twinning rate after IVF/ICSI has dropped by at least 50% simply by transferring only one good-quality embryo in the first and second fresh IVF/ICSI cycles in young women, without decrease in the overall pregnancy rate. Preventing 'the second half' of IVF/ICSI twins constitutes another and probably tougher challenge because the target group is a heterogeneous mix consisting of patients in very different clinical situations. Can we expand our experience for further twin prevention to women of older age and to cycles of higher rank without a significant drop in pregnancy rates? Can we extend it to more cryopreservation cycles? To have an idea of future target groups for increased application of SET, we analysed the remaining twins after double-embryo transfer (DET), and from these data we suggest expanding the eSET policy to women <38 years of age until the third cycle and to cryopreservation cycles.     

The cumulative embryo score: a predictive embryo scoring technique to select the optimal number of embryos to transfer in an in-vitro fertilization and embryo transfer programme.

In order to achieve a clinical pregnancy rate higher than that achieved following initial adoption of in-vitro fertilization embryo transfers, more than one embryo is transferred. This has led to a substantial increase in unwanted multiple pregnancy rates with IVF as compared with natural conception. What is therefore required is a simple, clinically useful embryo scoring system, to reflect embryo developmental potential, which will enable the selection of the optimal number of embryos to transfer in order to achieve the maximum pregnancy rate with a low incidence of high order multiple pregnancies. We believe that the Cumulative Embryo Score (CES) achieves these aims. On the day of embryo transfer the grade of each embryo transferred was multiplied by the number of blastomeres to produce a score for each embryo, and summation of the scores obtained for all the embryos transferred gave the CES. The grouped pregnancy rates obtained rose as the CES increased to maximum of 42. A continued increase in the CES above 42 did not result in any further rise in the pregnancy rate. However, an analysis of all our IVF pregnancies showed that the multiple pregnancy rate continued to rise above a CES of 42. By restricting the CES per embryo transfer to 42, 78% of triplet pregnancies and 100% of the quadruplet IVF pregnancies could have been predicted and potentially avoided.     

Genetics and human conception: DNA-based X-enriched sperm separation as an adjunct to preimplantation genetic testing for the prevention of X-linked disease

We report the world's first clinical pregnancy resulting fromDNA-based enrichment for X-bearing human spermatozoa, for preventionof X-linked hydrocephalus. Sperm separation was followed byembryo biopsy and nested multiplex polymerase chain reaction(PCR) for gender determination. Enriched populations of X-bearingspermatozoa ranging from 80 to 89% pure as determined by fluorescencein-situ hybridization (FISH) resulted in in-vitro fertilization(IVF) rates indistinguishable from normal IVF procedures (65%).In two separate biopsy procedures, 7/9 and 15/16 of the resultingembryos were determined to be female by multiplex PCR. Embryotransfer resulted in a karyotypically normal female fetus. Thistechnique should be widely applicable to gender selection forthe prevention of genetic disorders.     

Andrology: An indiscriminate use of pentoxifylline does not improve in-vitro fertilization in poor fertilizers

In order to enhance fertilization in vitro, pentoxifylline (PTX)was used in couples showing low fertilization rates in previousin-vitro fertilization (IVF) attempts for the treatment of malefactorinfertility. Sibling oocytes were inseminated at random withspermatozoa prepared with or without PTX. After selection byPercoll gradient, sperm samples were divided into two equalaliquots. One aliquot was incubated in Earle's medium containing3.6 mM PTX (treatment group), the other aliquot was incubatedwith PTX-free Earle's medium (control group). After 30 min,both suspensions were washed twice. Sperm parameters after preparationdid not differ between treatment and control samples, and nordid the mean fertilization rates, which were 49.3 and 42.6%respectively. Cleavage characteristics and morphological qualityof the embryos were not significantly different between thetreatment and control groups. The results of this study demonstratethat indiscriminate use of PTX in an IVF programme increasesneither fertilization rate nor embryo transfer rate in poorfertilizers. More prospective research is needed to evaluatethe role of PTX in IVF in couples selected according to theeffect of the compound on sperm function, e.g. hyperactivationand acrosome reaction.     

Comparison of outcome of pregnancy after intra-uterine insemination (IUI) and IVF

INTRODUCTION: Pregnancy outcome after IVF has been shown to be worse than after spontaneous conception. There is discussion as to whether this results from the technique itself or the patient characteristics. This study compares pregnancy outcome after IVF and intra-uterine inemination (IUI) in a matched patient group. METHODS: Data were obtained from our IVF and IUI databases (1997-2001). Matching was performed for maternal age, parity and plurality, and 126 IUI pregnancies were compared with 126 IVF pregnancies. Outcome variables were pregnancy duration, birth weight, Caesarean section rates, preterm contraction rates, neonatal intensive care unit admission, Apgar score, blood loss rates and maternal hypertension. RESULTS: None of the analysed parameters was statistically different between the groups. CONCLUSION: This matched case-control study does not show different pregnancy outcomes after IVF and IUI. Since there is no reason to believe that the IUI technique in itself leads to an increased obstetric or neonatal risk, this study suggests that the worse pregnancy outcome after IVF as compared with spontaneous conceptions is due to the specific patient characteristics, rather than to the use of IVF itself.     

Obstetric outcome of pregnancies after the transfer of cryopreserved and fresh embryos obtained by conventional in-vitro fertilization and intracytoplasmic sperm injection.

This study reports the obstetric outcome of pregnancies obtained after the transfer of cryopreserved or fresh embryos where the initial procedure was standard in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Pregnancies obtained after frozen IVF (n = 245) or frozen ICSI (n = 177) were compared with a control group of pregnancies after fresh embryo transfer in standard IVF (n = 245) and ICSI (n = 177) cycles were selected as controls. The controls were matched according to maternal age, parity and date of embryo transfer. In the standard IVF group, the biochemical pregnancy rates in the cryopreserved and fresh groups were 18.8 and 9.8% respectively (P < 0.01). In the ICSI group, the biochemical pregnancy rates in the cryopreserved and fresh groups were 16.4 and 6.8% respectively (P < 0.01). The miscarriage rates were comparable between the cryopreserved and fresh groups. However, in the frozen ICSI group the miscarriage rate (26.0%) was significantly higher than in the frozen conventional IVF group (13.1%) (P = 0.001). The frequencies of preterm deliveries, infants with very low birthweight and intrauterine deaths were similar in the groups. The low birthweight rates in the frozen IVF (16.1%) and ICSI (12.1%) groups were significantly lower than those in the fresh IVF (32.2%) and ICSI (32.7%) groups (P < 0.001). The major malformation rates in the frozen IVF (2.4%) and ICSI (2.9%) groups were not different from the major malformation rates in the fresh IVF (4.5%) and ICSI (2.4%) groups. In conclusion, the cryopreservation process had no negative impact on the outcome of pregnancies over 20 weeks of gestation. Long-term follow-up studies are needed in order to prove the safety of the freezing-thawing process.     

The effect on IVF outcome of small intramural fibroids not compressing the uterine cavity as determined by a prospective matched control study

BACKGROUND: Several studies have reported that the presence of intramural fibroids affects conception following IVF. We attempted to corroborate or refute the conclusions relating to IVF and leiomyomas of the aforementioned studies. METHODS: Women with small intramural leiomyomata (< or = 5 cm) discovered on initial pelvic sonographic studies performed in preparation for IVF were prospectively matched by age, with the next patient of the same age undergoing IVF who did not demonstrate fibroids (controls). RESULTS: Though no significant differences were found in outcome when comparing these two groups, there was a distinct trend for lower live delivery rates and higher miscarriage rates. CONCLUSIONS: These data support the conclusions of the only other prospective matched control study evaluating similar factors, i.e. that small intramural fibroids can negatively affect IVF outcome. Nevertheless, we think that a multicentre study should be conducted first before evaluating whether myomectomy improves outcome or not.     

A prospective, randomized study comparing day 2 and day 3 embryo transfer in human IVF

It is believed that delayed transfer of embryos after IVF allows for a better selection of good quality embryos. Hence, the number of embryos and all other prognostic factors being equal, transfer of day 3 embryos should be associated with higher implantation and pregnancy rates than transfer of day 2 embryos. To investigate this hypothesis, a prospective randomized study was carried out to compare implantation and pregnancy rates between day 2 and day 3 transfers. The relationship between the embryo quality score of day 2 and day 3 embryos and their respective implantation rates was also analysed. In a 2 year period all patients undergoing infertility treatment and in whom at least seven normally fertilized oocytes were obtained were included in the study. A minimization procedure was performed taking into account the patient's age and the method of fertilization (IVF or intracytoplasmic sperm injection). By using a uniform policy of embryo transfer, the number of embryos transferred was similar in both groups. The outcome parameters were embryo quality, implantation and pregnancy rates. No difference was observed in implantation and pregnancy rates between transfers on day 2 versus day 3 (23.8 versus 23.8% and 47.9 versus 46.8% respectively). The incidence of embryos of moderate to poor quality was higher in embryos cultured for 3 days compared with those cultured for 2 days. It is concluded that the outcomes of embryo transfer in terms of implantation and pregnancy rates are comparable for day 2 and day 3 embryos, although the overall embryo quality score decreases when embryos are kept in culture till day 3.     

Embryo selection in IVF

To optimize success rates of IVF, selection of the most viable embryo(s) for transfer has always been essential, as embryos that are cryopreserved are thought to have a reduced chance of implanting after thawing. Recent developments challenge this concept. Evidence is accumulating that all embryos can now be cryopreserved and transferred in subsequent cycles without impairing pregnancy rates or maybe even with an improvement in pregnancy rates. In such a scenario no selection method will ever lead to improved live birth rates, as, by definition, the live birth rate per stimulated IVF cycle can never be improved when all embryos are serially transferred. In fact, selection could then only lower the live birth rate after IVF. The only parameter that could possibly be improved by embryo selection would be time to pregnancy, if embryos with the highest implantation potential are transferred first.     

Shortened exposure of oocytes to spermatozoa improves in-vitro fertilization outcome: a prospective, randomized, controlled study.

A prospective, randomized study of 158 patients undergoing in-vitro fertilization (IVF) and embryo transfer was conducted to evaluate whether a shortened exposure of oocytes to spermatozoa enhances oocyte development, and subsequently influences the IVF outcome. A comparison was made between conventional treatment time and shorter exposure of retrieved oocytes to spermatozoa. Fertilization and cleavage rates, embryo quality, implantation and pregnancy rates in the study group (short exposure) versus controls (standard IVF procedure) were evaluated. Fertilization (56 versus 61%) and cleavage rates (96 versus 92%) were similar in the two groups respectively. However, embryo quality was significantly higher in the study group (P < 0.05). Moreover, the pregnancy and implantation rates were significantly increased (42.4 versus 26% per embryo transfer, and 16 versus 10% respectively; P < 0.05). Our results demonstrated that shorter exposure of oocytes to spermatozoa is superior to the standard time in IVF and may have a favourable effect on implantation rates by improving embryo quality.     

What is the most relevant standard of success in assisted reproduction?: The cumulated singleton/twin delivery rates per oocyte pick-up: the CUSIDERA and CUTWIDERA

National and international registries are essential tools for establishing new standards and comparing success rates, but they do not take into account the total pregnancy/delivery rate per oocyte recovery. In Switzerland and Germany, because of legal constraints, a maximum of three two-pronuclear zygotes are allocated for transfer whereas all the supernumerary pronuclear zygotes are immediately cryopreserved, preventing selection of the transferred embryos. We report on a 10 years' experience (1993-2002) of our centre which performs transfers of unselected embryos and cryopreservation at the two-pronuclear zygote stage. As approximately 30% of all deliveries are from cryo cycles, it is essential to take into account the contribution of the cryo transfers, and we propose therefore to evaluate, as a measure of IVF performance, the cumulated delivery rate per oocyte pick-up. This delivery rate is broken down further into the cumulated singleton delivery rate (CUSIDERA) and the cumulated twin delivery rate (CUTWIDERA). The sum (S) of these two rates is a measure of efficacy while the ratio CUTWIDERA/S as a percentage is a measure of safety of IVF treatments. Using these new indexes, the average 10 year efficacy and safety of our IVF programme were 26 and 19%, respectively. Both CUSIDERA and CUTWIDERA can be calculated easily in any clinical situation and yield useful parameters for patient counselling and internal/external benchmarking purposes.