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.     

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.     

Live birth rates after transfer of equal number of blastocysts or cleavage-stage embryos in IVF. A systematic review and meta-analysis

BACKGROUND: Both cleavage-stage and blastocyst-stage embryo transfer policies have advantages and drawbacks. The number of embryos transferred, however, is a crucial parameter that needs to be considered before attempting any comparison. METHODS: An extensive literature search yielded initially 282 studies from which 8 randomized controlled trials met the inclusion criteria: (i) truly randomized design (ii) policy to transfer equal number of embryos in both the cleavage-stage and the blastocyst-stage groups and (iii) published as full text in a peer-review journal. Primary outcome was the live birth rate and secondary outcomes were clinical pregnancy rate, multiple pregnancy rate, cancellation rate and cryopreservation rate. RESULTS: A total of 1654 patients were reviewed. Live birth rate per randomized patient was significantly higher (n = 6 studies) in patients who had a blastocyst-stage transfer as compared to patients with cleavage-stage embryo transfer [odds ratio (OR): 1.39, 95% confidence interval (CI): 1.10-1.76; P = 0.005]. Clinical pregnancy rate (OR: 1.27, 95% CI: 1.03-1.55; P = 0.02) and cancellation rate per patient randomized (OR: 2.21, 95% CI: 1.47-3.32; P = 0.0001) were significantly higher in patients with a blastocyst-stage embryo transfer as compared to patients in whom a cleavage-stage embryo transfer was performed. The cryopreservation rate was significantly higher in the cleavage-stage group (OR: 0.28, 95% CI: 0.14-0.55; P = 0.0002). CONCLUSIONS: The best available evidence suggests that the probability of live birth after fresh IVF is significantly higher after blastocyst-stage embryo transfer as compared to cleavage-stage embryo transfer when equal number of embryos are transferred in the two groups compared.     

What is the most relevant standard of success in assisted reproduction? Redefining success in the context of elective single embryo transfer: evidence, intuition and financial reality

Treatment-related multiple pregnancy poses the biggest threat to the safety of IVF. Despite a double embryo transfer (DET) policy in most European centres, twin rates continue to be unacceptably high, at 20-35%. Elective single embryo transfer (SET) is an effective way to minimize twin pregnancies, but the debate surrounding its routine clinical use continues. A review of the literature was undertaken in order to seek evidence about the effectiveness of SET, and identify barriers to its acceptance in clinical practice. Data from randomized controlled trials (RCTs) indicate that SET results in lower live birth rates per fresh IVF cycle (odds ratio 0.53; 95% confidence interval 0.31-0.89; P = 0.02) in comparison with DET. Data on cumulative live birth rates are unavailable from RCTs, although the expectation is that these are comparable in the two groups. SET is unlikely to be suitable for all women undergoing IVF and outcomes may be sensitive to different laboratory protocols. The perceived effectiveness of SET is influenced by the way existing evidence is interpreted. Other factors affecting the routine use of SET include laboratory techniques, individual preferences and funding issues.     

The couple's decision-making in IVF: one or two embryos at transfer?

BACKGROUND: The aim of this study was to evaluate the decision-making process and factors that contribute to the decision of IVF participants to choose one or two embryos at transfer. METHODS: Two hundred and seventy-four IVF patients equally distributed in males and females were personally interviewed using a semi-structured questionnaire which included 82 items. RESULTS: In the whole study population, previous childbirth [odds ratio (OR) 2.1; 95% confidence interval (CI) 1.9-3.6], and spare embryos to freeze (OR 23.6; 95% CI 11.2-54.5) emerged as the most important variables in patients who had one embryo transferred, while previous IVF treatments (OR 0.3; 95% CI 0.1-0.6) and the assumed increased pregnancy chance (OR 0.1; 95% CI 0.05-0.3) were the most important decision-making factors among those who had two embryos. The women were more satisfied with the information (83 versus 71%; P = 0.02), and more aware of the risks with twin pregnancies (77 versus 66%; P = 0.03) than the males. The women were also more concerned about their age. Knowledge about risks of multiple pregnancies was higher in females (77%) than in males (66%, P = 0.03). CONCLUSION: The results of this study indicate that despite good information about the risks for complications with multiple pregnancies, many patients wish to have two embryos transferred. Spare embryos to freeze, improvement of pregnancy rate in single embryo transfer and young age of the woman are predictive of choosing single embryo transfer. However, the final decision must always be made in agreement with the physician.     

Obstetric and neonatal outcome after single embryo transfer

BACKGROUND: Single embryo transfer (SET) pregnancies practically lack vanishing twins and may be associated with improved neonatal outcome. Our objective was to compare the obstetric and neonatal outcome of SET singletons with the outcome of singletons following double embryo transfer (DET) and spontaneous conception. METHODS: A 7-year (1997-2003) cohort of fresh SET (n = 269) and DET (n = 230, including 25 vanishing twins) cycles resulting in singleton birth at Helsinki University Central Hospital, Finland, was linked to the Finnish Medical Birth Register and the obstetric and neonatal outcome data compared with that from 15 037 spontaneously conceived singleton pregnancies. RESULTS: The obstetric and neonatal outcome of the SET group was comparable to that in the DET group. Compared with the comparison cohort, gestational hypertension (P = 0.005), placenta praevia (P < 0.001), preterm contractions (P = 0.01) and maternal hospitalization (P < 0.001) was more typical of women in the SET group. After adjusting for age, parity and socio-economic status the SET pregnancies showed increased risks of Caesarean section [odds ratio (OR) 1.54 with 95% confidence interval (CI) 1.18-2.00], preterm birth (OR 2.85; 95% CI 1.96-4.16) and low birthweight (OR 2.01; 95% CI 1.19-3.99) compared with the comparison cohort. CONCLUSIONS: Our results indicate that subject- and infertility-related mechanisms other than the number of transferred embryos influence the neonatal outcome of singleton IVF pregnancies.     

Elective single embryo transfer in women aged 36-39 years

BACKGROUND: The elective single embryo transfer policy is the only effective strategy known to minimize the risk of multiple pregnancy. However, little is known about its applicability to women older than 35 years. METHODS: Analysis was carried out on 1224 fresh IVF/ICSI cycles with embryo transfer and 828 frozen embryo transfer (FET) cycles of women aged 36-39 years. In the fresh cycles, 335 elective single top quality embryo (eSET), 110 elective single non top quality embryo (nt-eSET), 194 compulsory single embryo (cSET) and 585 double embryo transfers (DET) were carried out. RESULTS: Pregnancy rate/embryo transfer (33.1 versus 29.9%) and live birth rate (26.0 versus 21.9%) in fresh cycles did not differ significantly between the eSET and the DET groups. However, women in the eSET group had a higher cumulative pregnancy rate (54.0% versus 35.0%) and a higher cumulative live birth rate (41.8% versus 26.7%, P < 0.0001) compared with those in the DET group. The cumulative multiple birth rate in the eSET group was 1.7%, whereas in the DET group it was 16.6% (P < 0.0001). CONCLUSIONS: The eSET policy can be applied also to patients aged 36-39 years, reducing the risk of multiple birth and increasing the safety of assisted reproduction technique (ART) in this age group.     

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.     

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.     

Blastocyst Transfer Ameliorates Live Birth Rate Compared with Cleavage-Stage Embryos Transfer in Fresh In Vitro Fertilization or Intracytoplasmic Sperm Injection Cycles: Reviews and Meta-Analysis

Purpose

Blastocyst transfer has been recommended to raise the implantation rate without affecting the pregnancy rate. The objective of this meta-analysis is to systematically evaluate whether the live birth rate and other pregnancy outcomes can be improved by blastocyst transfer compared with cleavage-stage embryos transfer.

Materials and Methods

EMBASE and MEDLINE databases were searched for papers published between March 2004 and March 2013. An extensive range of the electronic databases yielded initially 317 studies from which seven trials met the inclusion criteria for further analysis. Our outcome measures were the live birth rate, clinical pregnancy rate, implantation rate, ongoing pregnancy rate, multiple pregnancy rate, first trimester miscarriage rate and ectopic pregnancy rate. Fixed effects models were chosen to calculate the odds ratio (OR).

Results

Seven trials (n=1446 cases) were finally analyzed. Compared with cleavage-stage embryos transfer, the blastocyst transfer was statistically significantly associated with an increase in clinical pregnancy rate [OR 1.43; 95% confidence interval (CI), 1.15-1.78], implantation rate (OR 1.38; 95% CI, 1.09-1.74) and ongoing pregnancy rate (OR 2.15; 95% CI, 1.57-2.94), and also a reduction in the probability of first trimester miscarriage rate (OR 0.51; 95% CI, 0.30-0.87). The improvement in the live birth rate was also observed (OR 1.77; 95% CI, 1.32-2.37). Moreover, there was no evidence of difference in multiple pregnancy and ectopic pregnancy rates.

Conclusion

The available evidences suggest that live birth and other pregnancy outcomes after fresh in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) are significantly improved following blastocyst transfer as compared to cleavage-stage embryo transfer.     

A randomized controlled clinical trial of 2295 ultrasound-guided embryo transfers

BACKGROUND: We wanted to test the hypothesis that using abdominal ultrasoundat the time of embryo transfer to guide replacement, improvedpregnancy rates by at least 5%. METHODS: An RCT in a large assisted conception unit. A pilot study andpower calculation suggested that at least 2000 embryo transferswere required to demonstrate a difference of 5%, for a testwith 80% power and Type 1 error 0.05. Randomization, data entryand analysis were arranged independently. Randomization wasstratified for age and fresh/frozen embryo transfer. Analysiswas by intention to treat. RESULTS: There was no difference in clinical pregnancy or live birthrates between the two groups. The clinical pregnancy rate forultrasound-guided embryo transfer was 22% and for non-ultrasound-guidedembryo transfer was 23% (odds ratio: 0.96; 95% confidence interval:0.79–1.18). CONCLUSIONS: We set out to determine whether ultrasound-guided embryo transferimproved clinical pregnancy rates and live birth rates in assistedconception. We used an appropriately powered RCT design. Wedid not demonstrate a difference. This outcome is at odds withthe UKs National Institute of Clinical Excellence recommendationsfor fertility treatment (Fertility Assessment and Treatmentfor People with Fertility Problems. London, UK: RCOG Press,2004, 112.) which used a meta-analysis of four smaller trials(range 362–800 patients, totalling 2051 embryo transfers)to conclude that ultrasound should be offered. We suggest thatthe current Cochrane review should be updated with data fromour trial and recommend that consideration is given to accountingfor heterogeneity between the included trials.     

Frozen embryo transfers: implications of clinical and embryological factors on the pregnancy outcome

BACKGROUND: Frozen embryo transfers are characterized by impaired pregnancy outcome and increased incidence of pregnancy loss as compared with fresh IVF/ICSI embryo transfers. In this study, we performed a retrospective analysis of clinical and embryological factors that potentially influence the outcome of frozen embryo transfer. METHODS: We reviewed the outcome of 1242 frozen embryo transfers with respect to the age of the woman, the method of fertilization, embryo quality before and after freezing and the number of embryos transferred. RESULTS AND CONCLUSIONS: The pregnancy (positive hCG) and clinical pregnancy rates were 25.8 and 21.1%, respectively. A total of 107 (33.3%) of the 321 pregnancies identified by a positive hCG test miscarried either before (18.4%) or after (15%) the clinical recognition of gestational sac(s). The delivery rate for the frozen embryo transfers analysed was 17.2%. Our data revealed that the delivery rate after frozen embryo transfer was dependent on both the woman's age and the quality of embryos transferred, at the same time being unaffected by IVF/ICSI treatment. In addition, the increased woman's age at IVF/ICSI treatment was identified as the only parameter elevating the biochemical pregnancy rate, whereas the clinical abortion rate was found to be unrelated to the clinical or embryological parameters studied.     

Minimal stimulation IVF with late follicular phase administration of the GnRH antagonist cetrorelix and concomitant substitution with recombinant FSH: a pilot study

BACKGROUND: The use of the natural cycle for IVF offers the advantage of a patient-friendly and low-risk protocol. Its effectiveness is limited, but may be improved by using a GnRH antagonist to prevent untimely LH surges. METHODS: In this pilot study, minimal stimulation IVF with late follicular phase administration of the GnRH antagonist cetrorelix and simultaneous substitution with recombinant FSH was applied for a maximum of three cycles per patient. Main outcome measures were pregnancy rates per started cycle and cumulative pregnancy rates after three cycles. RESULTS: A total of 50 patients completed 119 cycles (2.4 per patient). Fifty-two embryo transfers resulted in 17 ongoing pregnancies [14.3% per started cycle; 32.7% per embryo transfer; 95% confidence interval (CI) 7.9-20.7% and 19.7-45.7%, respectively]. One dizygotic twin pregnancy occurred after transfer of two embryos, the other pregnancies were singletons. The cumulative ongoing pregnancy rate after three cycles was 34% (95% CI 20.6-47.4%). Live birth rate was 32% per patient (95% CI 18.8-45.2%). CONCLUSIONS: Pregnancy rates after IVF with minimal, late follicular phase stimulation are encouraging. Considering the low-risk and patient-friendly nature of this protocol, it may be a feasible alternative to IVF with ovarian hyperstimulation.     

Live birth rate is significantly higher after blastocyst transfer than after cleavage-stage embryo transfer when at least four embryos are available on day 3 of embryo culture. A randomized prospective study

INTRODUCTION: In a randomized controlled trial, we assessed whether pregnancy outcome would be improved by extending embryo culture to day 5 and transferring a blastocyst in patients with at least four good-quality embryos on day 3. METHODS: Multifollicular ovarian stimulation was performed with a GnRH agonist in 44% of patients and with a GnRH antagonist in 56%. Overall, 164 patients younger than 37 years fulfilled embryo quality criteria (at least four having at least six cells on the morning of day 3, maximum 20% anucleate fragments) on the third day of culture and were randomized to the day 3 (n = 84) or day 5 (n = 80) groups. Equal numbers of embryos (n = 2) were transferred in each group. RESULTS: Demographics, stimulation parameters and embryological data were comparable in the two groups. Blastocyst-stage transfer resulted in a significantly higher ongoing pregnancy rate [51.3 versus 27.4%; odds ratio (OR) 2.78, 95% confidence interval (CI) 1.45-5.34] and live birth rate (47.5 versus 27.4%; OR 2.40, 95% CI 1.25-4.59) compared with day-3 embryo transfer. A high twin birth rate was observed in both groups (36.8 versus 30.4%; P > 0.05). CONCLUSIONS: A threshold of four good embryos on the third day of embryo culture appears to indicate that the patient will benefit from embryo transfer at the blastocyst stage and have a better chance of achieving a live delivery than with cleavage-stage embryo transfer.     

Laparoscopic salpingectomy for women with hydrosalpinges enhances the success of IVF: a Cochrane review

BACKGROUND: The aim of this study was to determine whether surgical intervention is effective for women with tubal disease who are due to undergo treatment with IVF. METHODS: A systematic review employing the principles of the Cochrane Menstrual Disorders and Subfertility Group was undertaken. Three randomized controlled trials were included, the population of women in all three studies having hydrosalpinges. RESULTS: The odds of pregnancy [odds ratio (OR) = 1.75, 95% confidence interval (CI) 1.07-2.86] and of ongoing pregnancy and live birth (OR = 2.13, 95% CI 1.24-3.65) were increased with laparoscopic salpingectomy for hydrosalpinges prior to IVF. There were no significant differences in the odds of embryo implantation (OR = 1.34, 95% CI 0.87-2.05), ectopic pregnancy (OR = 0.42, 95% CI 0.08-2.14), miscarriage (OR = 0.49, 95% CI 0.16-1.52) or treatment complications (OR = 5.80, 95% CI 0.35-96.79). No data were available concerning the odds of multiple pregnancy or the proportion of IVF cycles resulting in embryo transfer. CONCLUSION: Laparoscopic salpingectomy should be considered for all women with hydrosalpinges due to undergo IVF; further research is required to assess other pre-IVF surgical interventions (such as needle aspiration of hydrosalpinx fluid, laparoscopic proximal tubal occlusion and laparoscopic salpingostomy) for women with hydrosalpinges.     

Single versus double embryo transfer: cost-effectiveness analysis alongside a randomized clinical trial

BACKGROUND: Twin pregnancies after IVF are still frequent and are considered high-risk pregnancies leading to high costs. Transferring one embryo can reduce the twin pregnancy rate. We compared cost-effectiveness of one fresh cycle elective single embryo transfer (eSET) versus one fresh cycle double embryo transfer (DET) in an unselected patient population. METHODS: Patients starting their first IVF cycle were randomized between eSET and DET. Societal costs per couple were determined empirically, from hormonal stimulation up to 42 weeks after embryo transfer. An incremental cost-effectiveness ratio (ICER) was calculated, representing additional costs per successful pregnancy. RESULTS: Successful pregnancy rates were 20.8% for eSET and 39.6% for DET. Societal costs per couple were significantly lower after eSET (7334 euro) compared with DET (10,924 euro). The ICER of DET compared with eSET was 19,096 euro, meaning that each additional successful pregnancy in the DET group will cost 19,096 euro extra. CONCLUSIONS: One cycle eSET was less expensive, but also less effective compared to one cycle DET. It depends on the society's willingness to pay for one extra successful pregnancy, whether one cycle DET is preferred from a cost-effectiveness point of view.     

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.     

Single embryo transfer: a mini-review

This paper provides a concise review of single embryo transfer (SET) in cycles using fresh embryos as well as in cycles using frozen-thawed embryos. Relevant studies were identified by a computerized search in PubMed for the period 1995-2004. The pregnancy rates, delivery rates and multiple pregnancy/birth rates were evaluated after fresh or frozen embryo transfer as well as cumulative delivery rates after fresh and frozen SET. The results of four randomized controlled trials (RCT) and seven observational studies using fresh embryo transfers are analysed. No RCT with SET in freezing-thawing cycles was identified, while one observational study was identified. The effects of a change in the rules from the National Board of Health and Welfare in Sweden in 2003 regarding the implementation of SET in Sweden are summarized.     

Cost-effectiveness of a mild compared with a standard strategy for IVF: a randomized comparison using cumulative term live birth as the primary endpoint

BACKGROUND Conventional ovarian stimulation and the transfer of two embryos in IVF exhibits an inherent high probability of multiple pregnancies, resulting in high costs. We evaluated the cost-effectiveness of a mild compared with a conventional strategy for IVF. METHODS Four hundred and four patients were randomly assigned to undergo either mild ovarian stimulation/GnRH antagonist co-treatment combined with single embryo transfer, or standard stimulation/GnRH agonist long protocol and the transfer of two embryos. The main outcome measures are total costs of treatment within a 12 months period after randomization, and the relationship between total costs and proportion of cumulative pregnancies resulting in term live birth within 1 year of randomization. RESULTS Despite a significantly increased average number of IVF cycles (2.3 versus 1.7; P < 0.001), lower average total costs over a 12-month period (8333 versus euro10 745; P = 0.006) were observed using the mild strategy. This was mainly due to higher costs of the obstetric and post-natal period for the standard strategy, related to multiple pregnancies. The costs per pregnancy leading to term live birth were euro19 156 in the mild strategy and euro24 038 in the standard. The incremental cost-effectiveness ratio of the standard strategy compared with the mild strategy was euro185 000 per extra pregnancy leading to term live birth. CONCLUSIONS Despite an increased mean number of IVF cycles within 1 year, from an economic perspective, the mild treatment strategy is more advantageous per term live birth. It is unlikely, over a wide range of society's willingness-to-pay, that the standard treatment strategy is cost-effective, compared with the mild strategy.     

Maternal and neonatal outcomes in dichorionic twin pregnancies following IVF treatment: a hospital-based comparative study

Aim: To compare maternal, and neonatal outcomes in IVF/ICSI and spontaneously conceived dichorionic twin pregnancy. Method: We collected data regarding dichorionic twin pregnancies following in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI, n=162) with the transfer of fresh embryos as well as data regarding spontaneously conceived pregnancies (n=213) delivered after 28 weeks of gestation at the Department of Obstetrics and Gynecology, Renmin Hospital in Wuhan in the years of 2010-2013. We then compared maternal and neonatal outcomes between IVF/ICSI and spontaneous dichorionic twin pregnancies, with a subgroup analysis separating traditional IVF from ICSI pregnancies. Odds ratios (OR) for associations between IVF/ICSI and pregnancy outcomes were adjusted for maternal factors. Results: The mean maternal age and the percentage of primiparous women were significantly higher in the IVF/ICSI group. Multivariate analysis revealed that maternal outcomes were comparable in both groups with/without adjustment for maternal age and parity. However, IVF/ICSI twins were less likely to have birth weight discordance than those spontaneously conceived (unadjusted OR=0.526, 95% CI 0.297-0.932; adjusted OR=0.486, 95% CI 0.255-0.856). In subgroup analyses, these associations were confirmed in the IVF (adjusted OR=0.496, 95% CI 0.265-0.926), but not in the ICSI group (adjusted OR=0.500, 95% CI 0.139-1.807). Conclusion: IVF/ICSI treatment was not a risk factor for adverse maternal neonatal outcomes, but the risk for birth weight discordance is lower among IVF/ICSI twins.