Intrauterine administration of autologous peripheral blood mononuclear cells promotes implantation rates in patients with repeated failure of IVF-embryo transfer

BACKGROUND: There are few effective approaches to infertile patients with repeated failure in IVF-embryo transfer therapy. Since recent evidence suggests that some populations of maternal immune cells positively support embryo implantation, we have developed a new approach using peripheral blood mononuclear cells (PBMCs). METHODS: Patients who had not experienced successful pregnancy despite four or more IVF-embryo transfer sessions were enrolled in this study (n = 35, 35 cycles). PBMCs were obtained from patients on the day of oocyte retrieval and were cultured with HCG for 48 h. Two days later, PBMCs were freshly isolated from patients again, combined with cultured PBMC and then administered to the intrauterine cavity of the patients. Blastocyst transfer was performed on day 5, and the success of implantation in the PBMC-treated group was compared with that in the non-treated group. RESULTS: Clinical pregnancy rate, implantation rate and live birth rate in the PBMC-treated group (41.2, 23.4 and 35.3%; n = 17, 47 and 16, respectively) were significantly higher than those in the non-treated group (11.1, 4.1 and 5.5%; n = 18, 49 and 18, respectively). CONCLUSION: Intrauterine administration of autologous PBMC may be an effective approach to improve embryo implantation in patients with repeated IVF failures.     

The influence of the depth of embryo replacement into the uterine cavity on implantation rates after IVF: a controlled, ultrasound-guided study

BACKGROUND: Traditionally, embryo transfer after IVF has been performed blindly and placing the embryos approximately 1 cm below the fundal endometrial surface. However, it has been suggested that transferring embryos rather lower in the uterine cavity or high in the uterus may improve implantation rates. Nevertheless, there has not yet been a controlled trial to prove this theory. This prospective randomized study investigates the influence of the depth of embryo replacement on the implantation rate after embryo transfer carried out under transabdominal ultrasound guidance. METHODS: A total of 180 consecutive patients undergoing ultrasound-guided embryo transfer were randomized to three study groups according to the distance between the tip of the catheter and the uterine fundus at the moment of the embryo deposition in the lumen of the endometrial cavity: group 1: 10 +/- 1.5 mm; group 2: 15 +/- 1.5 mm; group 3: 20 +/- 1.5 mm. RESULTS: There was equal distribution between all three study groups regarding the main demographic and baseline characteristics of the patients, ovarian response, oocyte retrieval and IVF outcome, as well as the characteristics of embryo transfer and luteal phase support. The position of the catheter tip in relation to the fundal endometrial surface in groups 1 (10.2 +/- 0.9 mm), 2 (14.6 +/- 0.7 mm) and 3 (19.3 +/- 0.8 mm) was significantly different. Implantation rate was significantly higher (P < 0.05) in groups 2 (31.3%) and 3 (33.3%) compared with group 1 (20.6%). CONCLUSIONS: The depth of the embryo replacement into the uterine cavity may influence implantation rates, and thus it should be considered as an additional procedure among factors recently proposed as associated with successful embryo transfer after IVF.     

Hydrosalpinx and IVF outcome: cumulative results after salpingectomy in a randomized controlled trial.

BACKGROUND: A randomized controlled trial of salpingectomy prior to IVF in patients with hydrosalpinges has been conducted in Scandinavia. The results from the first transfer cycle have been published and clearly demonstrated an improved pregnancy outcome after salpingectomy had been performed in patients with hydrosalpinges large enough to be visible on ultrasound. The present article is aimed at analysing the effect of salpingectomy on cumulative birth rate, including all individual transfer cycles. METHODS AND RESULTS: A total of 186 women underwent 452 cycles. Among the 77 women randomized to no surgical intervention, 24 underwent salpingectomy after one or two failed cycles. Cumulative results were analysed by Cox regression, taking into account the number of cycles per patient and the presence of a salpingectomy after a previous transfer. Salpingectomy implied a significant increase in birth rate (hazard ratio 2.1, 95% CI 1.6-3.6, P = 0.014). Within the subgroup of patients with ultrasound-visible hydrosalpinges, the birth rate was even higher (hazard ratio 3.8, 95% CI 1.5-9.2, P = 0.004). Implantation rate was significantly higher in patients who had undergone salpingectomy (27.2% versus 20.2, P = 0.03) and, in the subgroup of patients with ultrasound-visible hydrosalpinges, the difference was even larger (30.3% versus 17.1%, P = 0.003). CONCLUSIONS: The results of the cumulative cycles strengthen the recommendation for a laparoscopic salpingectomy prior to IVF in patients with ultrasound-visible hydrosalpinges.     

Comparison of a fixed and dynamic protocol for embryo replacement in an IVF/ET programme

Implantation after embryo transfer is considered a major obstadein terms of pregnancy rates after in-vitro fertilization. Aflexible approach to the date of replacement, based on the factthat the most suitable embryonic structure for proper implantationis the four- to eight-cell embryo, has been studied. One-hundred-and-twentypatients with various aetiologies of infertility were stimulatedwith HMG or combined HMG and FSH, then treated by three differentmethods of embryo replacement. In group I embryos were replacedin mothers 48 h after ovum retrieval; in group II replacementswere carried out 72 h after retrieval; and in group III replacementswere related to embryonic cleavage development. Mean levelsof oestradiol when HCG was given averaged 1301 ± 121pg/ml, 1016 ± 96 pg/ml and 1182 ± 101 pg/ml inthe three groups, respectively. There was no significant differencein the average number of embryos transferred among the variousgroups. The pregnancy rates per transfer were 21.8, 24.2 and38.7%, respectively (P < 0.001). Although more investigationis required, a dynamic approach to embryo replacement mightsignificantly improve pregnancy rates, because of improved interactionsbetween the embryos and the uterus.     

Ureaplasma in semen and IVF

Ureaplasma urealyticum (U.U.) screening has been systematicallyperformed in tests carried out before IVF cycles. In 42% ofthe cases (306 couples), at least one partner presented a monomicrobianU.U. infection. U.U. infection of at least one fraction of thesplit ejaculate was observed in 32% of the cases and found insimilar proportions at the prostatic and seminal vesicle levels.The U.U.-infected group presented a similar number of cytologicalabnormalities to the non infected samples. However, there wasa significant reduction in the pregnancy rate after embryo transferin the infected group whereas U.U. did not alter fertilizationparameters, embryo retrieval or pregnancy rates per puncture.The preliminary results of a complementary prospective study(70 couples) point to the likely role of sexually transmittedUreaplasma at the endometrial level.     

The merits of blastocyst versus cleavage stage embryo transfer: a Cochrane review

This paper is based on a Cochrane review published in The Cochrane Library, issue 2, 2002 (see www.CochraneLibrary.net for information) with permission from The Cochrane Collaboration and John Wiley and Sons. Cochrane reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and The Cochrane Library should be consulted for the most recent version of the review. BACKGROUND: The aim of this study was to determine the relative merits of blastocyst versus cleavage stage embryo transfer, concerning the chance of pregnancy, live birth, multiple pregnancy and the factors contributing to these primary outcomes, from the best available evidence. METHODS: A systematic review employing the principles of the Cochrane Menstrual Disorders and Subfertility Group was undertaken. Fourteen randomized controlled trials, all comparing day 2/3 with day 5/6 embryo transfer, were included in a meta-analysis. RESULTS: For day 2/3 versus day 5/6 transfer, there was no significant difference in the odds of pregnancy [odds ratio (OR) = 0.91, 95% confidence interval (CI) 0.71-1.17] nor of live birth (OR = 0.83, 95% CI 0.48-1.42) per treated couple. These results were similar whether all trials, only trials with transfer of equal numbers of day 2/3 versus day 5/6, or only trials with transfer of fewer day 5/6 than day 2/3 embryos, were pooled. There was no significant difference in the odds of multiple pregnancy for day 2/3 versus day 5/6 transfer overall (OR 0.77, 95% CI 0.52-1.13) nor when fewer day 5/6 than day 2/3 embryos were transferred (day 2/3 versus day 5/6 OR 0.69, 95% CI 0.42-1.12). CONCLUSION: The current evidence fails to support a widespread change of practice from cleavage stage to blastocyst stage embryo transfer in couples undergoing IVF.     

A randomized controlled trial of a soft double lumen embryo transfer catheter versus a firm single lumen catheter: significant improvements in pregnancy rates

BACKGROUND: Embryo transfer has changed little since originally described in 1978. Clinicians rate the type of catheter used as the third most important variable in embryo transfer, but there are no adequately powered randomized trials. We compared the clinical pregnancy rates with the single lumen catheter (TCC) and the double lumen catheter (CC) in a randomized single blind trial. METHODS: A total of 650 cycles of women from the Adelaide University reproductive medicine units in Australia were included in this trial. Patients were <40 years of age undertaking IVF and embryo transfer. Exclusion criteria were: known uterine abnormality, day 3 FSH >10 IU/l, previous difficult embryo transfer and pre-implantation genetic diagnosis. Cycles were randomized from numbered sealed envelopes immediately prior to embryo transfer with stratification for fresh or frozen cycles. RESULTS: There was a significantly higher pregnancy rate in the group treated with the CC compared with the TCC catheter [29.6 versus 20.5% per embryo transfer, odds ratio (OR) = 1.63 (95% confidence interval: 1.14-2.30), P = 0.0076]. The point estimate for the OR was similar for fresh and frozen cycles. CONCLUSIONS: The pregnancy rate was increased by 50% and this justifies the increased cost of the soft double lumen catheter and the training of clinical staff required.     

GnRH antagonist versus long GnRH agonist protocol in poor responders undergoing IVF: a randomized controlled trial

BACKGROUND. This is the first published report of a prospective, randomized, controlled trial comparing a fixed, multi-dose GnRH antagonist protocol with a long GnRH agonist protocol in poor responders undergoing IVF. METHODS. Sixty-six poor responders were randomized into two groups: the study group received 0.25 mg of cetrorelix daily starting on day 6 of stimulation; the control group received 600 microg of buserelin acetate daily starting in the mid-luteal phase of the preceding cycle. Both groups were given a fixed dose of recombinant FSH (300 IU daily) for stimulation. RESULTS. There were no significant differences in the cycle cancellation rates, duration of stimulation, consumption of gonadotrophins, and mean numbers of mature follicles, oocytes and embryos obtained. The implantation rates were similar, but the number of embryos transferred was significantly higher for the antagonist group (2.32 +/- 0.58 versus 1.50 +/- 0.83; P = 0.01). The pregnancy rates were also higher in the antagonist group, but the difference was not statistically significant. CONCLUSION. A fixed multi-dose GnRH antagonist protocol is feasible for patients who are poor responders on a long agonist protocol; however, our study failed to demonstrate an overall improvement in ovarian responsiveness. Clinical outcomes may be improved by developing more flexible antagonist regimens, an approach that requires further evaluation.     

Soft versus firm embryo transfer catheters for assisted reproduction: a systematic review and meta-analysis

BACKGROUND: The true impact of the embryo transfer catheter choice on an IVF programme has not been fully examined. We therefore decided to systematically review the evidence provided in the literature so that we may evaluate a single variable in relation to a successful transfer, the firmness of the embryo transfer catheter. METHODS: An extensive computerized search was conducted for all relevant articles published as full text, or abstracts, and critically appraised. In addition, a hand search was undertaken to locate any further trials. RESULTS: A total of 23 randomized controlled trials (RCT) evaluating the types of embryo transfer catheters were identified. Only ten of these trials, including 4141 embryo transfers, compared soft versus firm embryo catheters. Pooling of the results demonstrated a statistically significantly increased chance of clinical pregnancy following embryo transfer using the soft (643/2109) versus firm (488/2032) catheters [P = 0.01; odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.08-1.79]. When only the truly RCT were analysed, the results were again still in favour of using the soft embryo transfer catheters [soft (432/1403) versus firm (330/1402)], but with a greater significance (P < 0.00001; OR = 1.49, 95% CI = 1.26-1.77). CONCLUSION: Using soft embryo transfer catheters for embryo transfer results in a significantly higher pregnancy rate as compared to firm catheters.     

Elevated progesterone at initiation of stimulation is associated with a lower ongoing pregnancy rate after IVF using GnRH antagonists

BACKGROUND: The objective of this prospective study was to assessthe impact of elevated serum progesterone levels on day 2of the cycle on pregnancy rates in patients treated by IVF usingGnRH antagonists. METHODS: Ovarian stimulation was started onday 2 of the cycle if progesterone levels were normal (normal-Pgroup, n = 390). In the presence of elevated progesterone, initiationof stimulation was postponed for 1 or 2 days (high-P group,n = 20) and was started if repeat progesterone levels returnedto normal range (n = 16). Stimulation was performed with recombinantFSH (rFSH) and GnRH antagonist was always started on day 6of stimulation. RESULTS: A significantly higher exposure toprogesterone and a significantly lower exposure to estradiolwas present in the high-P as compared with the normal-P groupfrom day 1 to day 8 of stimulation. In addition, a significantlylower ongoing pregnancy rate both per started cycle (5.0% versus31.8%; P = 0.01) and per embryo transfer (6.3% versus 36.9%;P = 0.01) was present in the high-P compared with the normal-Pgroup, respectively. CONCLUSIONS: The presence of elevated serumprogesterone on day 2 of the cycle is associated with a decreasedchance of pregnancy in patients treated with rFSH and GnRH antagonists.     

Randomized single versus double embryo transfer: obstetric and paediatric outcome and a cost-effectiveness analysis

BACKGROUND: Transfer of several embryos after IVF results in a high multiple birth rate associated with increased morbidity and high costs for the neonatal care. In a previous randomized trial we demonstrated that a single embryo transfer (SET) strategy, including one fresh single embryo transfer and, if no live birth, one additional frozen-thawed SET, resulted in a live-birth rate that was not substantially lower than after double embryo transfer (DET) but markedly reduced the multiple birth rate. METHODS: We compared costs for maternal health care and productivity losses and paediatric costs for the SET and DET strategies. In addition, maternal and paediatric outcomes between the two groups were compared. RESULTS: The SET strategy resulted in lower average total costs from treatment until 6 months after delivery. There were a few more deliveries with at least one live-born child in the DET group. The incremental cost per extra delivery in the DET alternative was high, 71 940. The rates of prematurely born and low birthweight children were significantly lower with the SET strategy. There were also markedly fewer maternal and paediatric complications in the SET group. CONCLUSIONS: The SET strategy is superior to the DET strategy, when number of deliveries with at least one live-born child, incremental cost-effectiveness ratio and maternal and paediatric complications are taken into consideration. The findings do not support continuing transfers of two embryos in this group of patients.     

Timing luteal phase support in GnRH agonist down-regulated IVF/embryo transfer cycles

BACKGROUND: The aim of this study was to compare the effect of three different times of onset of luteal phase support on ongoing pregnancy rate in infertile patients undergoing treatment with GnRH down-regulated IVF and embryo transfer (IVF/ET). MATERIALS AND METHODS: All consecutive eligible patients planned to undergo their first IVF treatment cycle were randomly allocated to receive vaginal progesterone as luteal support at three different time points, that is, after HCG administration for final oocyte maturation (HCG group), at the day of oocyte retrieval (OR group) or at the day of ET (ET group). The primary endpoint of this study was ongoing pregnancy rate. RESULTS: A total of 385 women were randomized, 130 were allocated to the HCG group, 128 to the OR group and 127 to the ET group. An ongoing pregnancy rate of 20.8% was found in the HCG group versus 22.7 and 23.6% in the OR group and ET group, respectively. The mean number and quality of the retrieved oocytes and the transferred embryos did not differ. CONCLUSION: Based on this data, an 18% difference in ongoing pregnancy rate between the three different times of onset of luteal phase support in GnRH agonist down-regulated IVF/ET cycles can be refuted. Smaller clinically meaningful differences may be present.     

Two cycles with single embryo transfer versus one cycle with double embryo transfer: a randomized controlled trial

BACKGROUND: With the aim of reducing the number of multiple pregnancies after IVF we investigated the effectiveness of two cycles with single embryo transfer (SET) and one cycle with double embryo transfer (DET) after IVF and calculated the cost-effectiveness of both strategies. Methods: A randomized controlled trial was performed in 107 women, aged <35 years, in their first IVF cycle, with at least one good quality embryo. They were randomized to the SET (n = 54) or DET (n = 53) group using a computer-generated random block number table, stratified for primary or secondary infertility. RESULTS: The cumulative live birth rates per woman randomized of two consecutive cycles of SET [41%; 95% confidence interval (CI) 27-54] versus one cycle of DET (36%; 95% CI 23-49) were comparable, whereas the multiple pregnancy rate was significantly higher: 37% (95% CI 15-59) in the DET and 0% in the in the SET group (P = 0.002). Combining the medical costs of the IVF treatments (where 1.5 more SET cycles were required to achieve each live birth) and of pregnancies up to 6 weeks after delivery, the total medical costs of DET per live birth were 13,680 and 13,438 for SET. CONCLUSIONS: Two cycles with SET were equally effective as one cycle with DET, and the medical costs per live birth up to 6 weeks after delivery were the same. However, if lifetime costs for severe handicaps are included, more than 7000 per live birth will be saved after implementing SET. Because of the high probability of multiple pregnancies in this group of IVF patients, only SET should be performed.     

High serum oestradiol concentrations in fresh IVF cycles do not impair implantation and pregnancy rates in subsequent frozen-thawed embryo transfer cycles

High oestradiol concentrations may be detrimental to the success of in-vitro fertilization (IVF) treatment. A total of 1122 women aged <40 years who were undergoing their first IVF cycle were evaluated retrospectively. Serum oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration were categorized into three groups: group A <10 000 pmol/l; group B 10 000-20 000 pmol/l and group C >20 000 pmol/l. In fresh cycles, group A had significantly lower pregnancy rates per transfer (16.2 versus 23.7% respectively, P = 0.005, chi(2)) and implantation rates (8.7 versus 11.7% respectively, P = 0.037, chi(2)), when compared with group B. The pregnancy rate per transfer in group C was significantly lower than that in group B (12.1 versus 23.7%, P = 0.049, chi(2)) and group C had the lowest implantation rate (6.4%). In frozen-thawed embryo transfer cycles, implantation rates in groups A, B and C were similar (7.5, 8.1 and 9.6% respectively) and the pregnancy rates were also comparable in all groups. In conclusion, high serum oestradiol concentrations in fresh IVF cycles may adversely affect implantation and pregnancy rates. Embryo quality seemed unaffected as excess embryos from different groups had similar implantation and pregnancy rates in frozen-thawed embryo transfer cycles. The reduced implantation was probably due to an adverse endometrial environment resulting from high serum oestradiol concentrations.     

Effect of oral contraceptive pill pretreatment on ongoing pregnancy rates in patients stimulated with GnRH antagonists and recombinant FSH for IVF. A randomized controlled trial

BACKGROUND: The objective of this randomized controlled trial was to assess the effect of oral contraceptive pill (OCP) pretreatment on the probability of ongoing pregnancy in patients treated with a GnRH antagonist for IVF. METHODS: A fixed dose of 200 IU recombinant FSH (rFSH) was started in 425 patients either on day 2 of the menstrual cycle (non-OCP group: n = 211) or 5 days after discontinuing the OCP (OCP group: n = 214). GnRH-antagonist was initiated on day 6 of stimulation, and triggering of final oocyte maturation was performed with 10,000 IU of HCG. RESULTS: Ongoing pregnancy rates per started cycle in the non-OCP and OCP group were 27.5% and 22.9%, respectively [95% confidence interval (CI) of the difference: -3.7 to +12.8]. Pregnancy loss was significantly increased in the OCP (36.4%) compared with the non-OCP group (21.6%) (95% CI of the difference: -28.4 to -2.3). CONCLUSION: Pretreatment with OCP, as compared with initiation of stimulation on day 2 of the cycle in patients treated with GnRH antagonist and recombinant FSH, appears to be associated with a not significant difference in ongoing pregnancy rates per started cycle and results in a significantly higher early pregnancy loss.     

A randomized comparison of alternative methods of information provision on the acceptability of elective single embryo transfer

BACKGROUND: The purpose of this study was to assess the effect of alternative ways of providing information about the risks of twins on couples' perceptions about elective single embryo transfer (eSET). METHODS: Couples undergoing IVF were randomized into three groups. Group 1 received a standard information pack, group 2 an extra information leaflet about twin pregnancy, and group 3 an additional discussion session. The primary outcome measure was acceptability of a hypothetical policy of eSET. Data were collected by means of a questionnaire. RESULTS: eSET was acceptable to 17 (27%), 20 (30%) and 24 (32%) couples in groups 1, 2 and 3, if it meant a slight reduction in pregnancy rates, and to 51 (82%), 55 (83%) and 53 (87%) couples, respectively, if pregnancy rates were unchanged. A fixed charge for all fresh and frozen embryo transfers following a single oocyte retrieval led to acceptability rates of 35 (57%), 36 (55%) and 38 (65%). CONCLUSIONS: Additional information, involving an extra information leaflet and face to face discussion, did not changes couples' attitudes towards eSET. Maintaining existing rates of pregnancy and offering a fixed charge for all embryo transfers resulting from an oocyte recovery may encourage more couples to consider eSET.     

Predicting ongoing pregnancy chances after IVF and ICSI: a national prospective study

BACKGROUND: The Dutch IVF guideline suggests triage of patients for IVF based on diagnostic category, duration of infertility and female age. There is no evidence for the effectiveness of these criteria. We evaluated the predictive value of patient characteristics that are used in the Dutch IVF guideline and developed a model that predicts the IVF ongoing pregnancy chance within 12 months. METHODS: In a national prospective cohort study, pregnancy chances after IVF and ICSI treatment were assessed. Couples eligible for IVF or ICSI were followed during 12 months, using the databases of 11 IVF centres and 20 transport IVF clinics. Kaplan-Meier analysis was performed to estimate the cumulative probability of an ongoing pregnancy, and Cox regression was used for assessing the effects of predictors of pregnancy. RESULTS: 4928 couples starting IVF/ICSI treatment were prospectively followed. On average, couples had 1.8 cycles in 12 months for both IVF and ICSI. The 1-year probability of ongoing pregnancy was 44.8% (95% CI 42.1-47.5%). ICSI for severe oligospermia had a significantly higher ongoing pregnancy rate than IVF indicated treatments, with a multivariate Hazard ratio (HR) of 1.22 (95% CI 1.07-1.39). The success rates were comparable for all diagnostic categories of IVF. The highest success rate is at age 30, with a slight decline towards younger women and women up to 35 and a sharp drop after 35. Primary subfertility with a HR of 0.90 (95% CI 0.83-0.99) and duration of subfertility with a HR of 0.97 (95% CI 0.95-0.99) per year significantly affected the pregnancy chance. CONCLUSIONS: The most important predictors of the pregnancy chance after IVF and ICSI are women's age and ICSI. The diagnostic category is of no consequence. Duration of subfertility and pregnancy history are of limited prognostic value.     

Blastomere development after embryo biopsy: a new model to predict embryo development and to select for transfer

One of the most important and unsolved problems in in-vitro fertilization is to decide which embryos are more suitable to implant and therefore should be transferred. We analysed the in-vitro development of isolated biopsied blastomeres and compared it to the development of the original embryo, in order to find a relationship that could show the embryo's potential future development and so increase implantation rates. A total of 66 normally fertilized human embryos were biopsied at the 6- to 10-cell stages. At day 6, blastomeres were counted by nuclear labelling. A total of 33 embryos (50%) reached the blastocyst stage. Of the isolated blastomeres, 63% divided and 53% cavitated over 3 days in culture. Of the blastomeres taken from embryos that developed to the blastocyst stage, 88% divided, 79% cavitated, 76% divided and cavitated and 9% neither divided nor cavitated. In those from arrested embryos, 39% divided (P < 0.001), 21% cavitated (P < 0.001), 15% divided and cavitated (P < 0.001) and 55% neither divided nor cavitated (P < 0.001). Blastomeres biopsied from embryos that reached the blastocyst stage showed a significantly higher proportion of division and cavitation than those originated from arrested embryos. Culture of the isolated blastomeres can demonstrate those embryos more likely to develop to the blastocyst stage and that are probably more suitable to implant. Cryopreserving biopsed embryos and culturing blastomeres would increase implantation rates. Embryos can then be selected according to the blastomere development and thawed for transfer in a future cycle.     

IVF with preimplantation genetic screening, a promising new treatment with unexpectedly negative health outcomes: the Hippocratic role of Data Monitoring Committees

A recently published randomized controlled trial showed preimplantation genetic screening (PGS) as part of an IVF programme to reduce ongoing pregnancy rates by 1/3 in comparison to the control group without PGS: rate ratio (RR) 0.69 (0.51-0.93), P = 0.01. A masked interim analysis already showed significant differences between treatment arms: RR 0.58 (0.35-0.94), P = 0.02. Despite this finding, the trial's Data Monitoring Committee decided not to stop, but to continue the trial. This paper argues why this decision was sound, since it was based on (i) explicit statistical criteria and (ii) the trade-off between risks and benefits for current and future IVF patients. The trial's findings confront the medical community once again with the general problem of new technologies being implemented without randomized evidence of effectiveness.     

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).