How do cumulative live birth rates and cumulative multiple live birth rates over complete courses of assisted reproductive technology treatment per woman compare among registries?

STUDY QUESTION: How do the national cumulative (multiple) live birth rates over complete assisted reproduction technology (ART) courses of treatment per woman in Belgium compare to those in other registries? SUMMARY ANSWER: Cumulative live birth rates (CLBRs) remain high with a low cumulative multiple live birth rate when compared with other registries and publications. WHAT IS KNOWN ALREADY: In ART, a reduction in the multiple live birth rate could be achieved by reducing the number of embryos transferred. It has been shown that by doing so, live birth rates per cycle were maintained, particularly when the augmentation effect of attached frozen-thawed cycles was considered. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study included all patients with a Belgian national insurance number who were registered in the national ART registry (Belrap) and who started a first fresh ART cycle between 1 July 2009 until 31 December 2011 with follow up until 31 December 2012. We analysed 12 869 patients and 38 008 cycles (both fresh and attached frozen cycles). PARTICIPANTS, MATERIALS, SETTINGS, METHODS: CLBRs per patient who started a first ART cycle including fresh and consecutive frozen cycles leading to a live birth. Conservative estimates of cumulative live birth assumed that patients who did not return for treatment had no chance of achieving an ART-related live birth, whereas optimal estimates assumed that women discontinuing treatment would have the same chance of achieving a live birth as those continuing treatment. A maximum of six fresh ART cycles with corresponding frozen cycles was investigated and compared with other registries and publications. MAIN RESULTS AND ROLE OF CHANCE: The CLBR was age dependent and declined from 62.9% for women <35 years, to 51.4% for women 35-37 years, to 34.1% for women 38-40 years and 17.7% for women 41-42 years in the conservative analysis after six cycles. In the optimal estimate, the CLBR declined from 85.9% for women <35 years, to 72.0% for women 35-37 years, to 50.4% for women 38-40 years and 36.4% for women 41-42 years. The cumulative multiple live birth rates for the whole population were 5.1 and 8.6% for the conservative and optimal estimate, respectively. LIMITATIONS, REASONS FOR CAUTION: Conservative and optimal estimates use assumptions for the whole ART population and do not take the individual patient into account. WIDER IMPLICATIONS OF THE FINDINGS: These data reinforce the validity of the Belgian model of coupling reimbursement of ART costs to a restriction in the number of embryos transferred. Our data can improve decision-making in medical ART practice both on the patient level and for society at large and could provide health care takers and insurance companies with a valid model. STUDY FUNDING COMPETING INTERESTS: none.

Single embryo transfer and multiple pregnancy rate reduction in IVF/ICSI: a 5-year appraisal.

One of the most problematic issues of assisted reproduction is the high incidence of multiple pregnancies, resulting from the transfer of more than one embryo. Particularly at risk are young women who have good quality embryos. The only strategy to reduce the incidence of multiple pregnancies, including twin pregnancies, after assisted reproduction is single embryo transfer (SET). In 1997, the present authors therefore introduced elective SET (eSET) in this particular target group. The proportion of eSET increased from 1.5 (1997-1998) to 17.5% (1999-2002) of all transfers. In 2002, 20% of all transfers were SET. Comparing these two periods, an overall pregnancy rate of 35 and 34% per transfer, respectively, was obtained, while the overall twinning rate dropped from 30 to 21%. The twinning rate dropped to 14% in 2002, and in the eSET group there was only one monozygotic twin. These results demonstrate that a decline in the twinning rate is feasible without a drop in overall pregnancy rates. Comparing eSET with elective double embryo transfer (eDET), it was found that ongoing pregnancy and implantation rates were the same in both groups, but the proportion of twins was clearly different. It was further observed that the mean birthweight of singleton children born after eSET was significantly higher than that after DET. This could reflect a better developmental or implantation potential of these embryos, but this finding remains to be confirmed.

Transport-in-vitro fertilization/intracellular sperm injection: a prospective randomized study.

We performed a prospective randomized clinical trial to investigate whether long distance oocyte transport prior to an intracytoplasmic sperm injection (ICSI) procedure influences fertilization rates, embryo quality and/or embryo implantation rates. After informed consent, 100 infertile couples booked for ICSI treatment were randomized into two groups. In group 1 (n = 50), patients were stimulated and monitored in Rotterdam (The Netherlands), and oocyte retrieval, ICSI procedure and embryo transfer took place in Gent (Belgium). In group 2 (n = 50), patients were stimulated, monitored and punctured in Rotterdam and the oocytes were transported in their follicular fluid in an isothermic transport box to Gent, where the ICSI procedure and the embryo transfer took place. In both groups the stimulation and monitoring regimen, puncture technique, laboratory conditions and transfer policy were identical. In both groups, the number of fertilized oocytes (7.13 +/- 0.65 versus 5.53 +/- 0.60, P = 0.08), the number of transferred embryos (2.36 +/- 0.09 versus 2.40 +/- 0.11, P = 0.87) and the embryo implantation rate [20/113 (17.7%) versus 19/103 (18.4%), P = 0.89] was similar. In group 1, the number of retrieved oocytes was higher (10.83 +/- 0.95 versus 8.44 +/- 0.93, P = 0.05). The total score of the embryos obtained (18.90 +/- 1.73 versus 12.64 +/- 1.26, P = 0.01), the number of good quality embryos (4.63 +/- 0.49 versus 2.98 +/- 0.38, P = 0.02), the mean score of the transferred embryos (3.32 +/- 0.11 versus 2.94 +/- 0.13, P = 0.05) and the number of embryos available for cryopreservation (2.70 +/- 0.45 versus 1.48 +/- 0.38, P = 0.03) were significantly higher in group 1. Therefore, long distance transport of oocytes prior to ICSI does not affect oocyte fertilization and embryo implantation rates, although a negative effect on embryo quality cannot be excluded.

Transport intracytoplasmic sperm injection (ICSI): a cost-effective alternative.

PURPOSE: Transport in vitro fertilization (IVF) programs are operational in a lot of countries and especially popular in The Netherlands, where IVF activities are strictly regulated. Since the introduction of intracytoplasmic sperm injection (ICSI) in the IVF laboratory, many laboratories are now setting up this new technique, which necessitates major investments in terms of infrastructure and specialized personnel. METHODS: We present a cost effective alternative, consisting of patient selection, preparation, and oocyte retrieval at one center and transport of oocytes to a second center, where the ICSI procedure and embryo transfer are performed. Since early 1994 several Dutch centers have a transport ICSI program running with the Gent University Infertility Center, and we wish to present the results of our cooperation with two major centers, comparing them to our local results, for the first 10 months of 1994. Patient selection was similar at all three centers: only couples with previously failed in vitro fertilization or having been refused for routine IVF were enrolled in the program. Stimulation schemes and follow-up of the stimulation were different at all three centers. Transport of oocytes was carried out in a transport box or by attaching the closed tubes containing the follicular aspirates to the chest of the husband. Transport times varied between 1.5 and 3 hr, depending on traffic conditions. RESULTS: Up to November 1, 1994, a total of 77 transport ICSI cycles and 294 own ICSI cycles were carried out. Although locally significantly more oocytes were retrieved and thus available for ICSI than in transport cycles, fertilization and pregnancy rates were not different between the two groups. CONCLUSIONS: These results suggest that long-distance transport of human oocytes seems not to be harmful to their capacity to be successfully injected and to further embryonic development and their implantation potential. Transport ICSI seems to be a valuable and cost-effective approach to treat high numbers of patients at a restricted number of highly specialized IVF laboratories, especially in countries where ICSI is not commonly available.

Complete and partial luteinized unruptured follicle syndrome after ovarian stimulation with clomiphene citrate/human menopausal gonadotrophin/human chorionic gonadotrophin.

A total of 31 clomiphene citrate/human menopausal gonadotrophin (HMG)/human chorionic gonadotrophin (HCG)-stimulated cycles in 28 patients were investigated to determine the fate of each of the matured follicles. A standard stimulation regimen was adhered to, and ultrasound as well as hormonal monitoring was performed. All follicles were measured by vaginal ultrasound at -12, +35 and +45 h relative to HCG administration and at 7 days after HCG administration. Of the 220 follicles, 107 (48.6%) ruptured. The number of ruptured follicles per cycle was correlated with the mid-luteal progesterone concentration (r = 0.63, P = 0.0005). The probability of follicular rupture was related to follicular diameter at 12 h before HCG administration; 6% of follicles < 12 mm in diameter ruptured compared with 87% of follicles 18-19 mm. A complete luteinized unruptured follicle (LUF) syndrome was observed in six cycles (20%). In these cycles, follicular growth and oestradiol, progesterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations at 12 h before HCG administration were similar to those in cycles with follicular rupture. However, mid-luteal progesterone concentrations were lower in complete LUF cycles (46.97 +/- 8.95 nmol/l versus 108.74 +/- 12.27 nmol/l; P = 0.02). These data demonstrate that in stimulated cycles many follicles, usually the smaller ones, fail to rupture, even after HCG administration. Complete LUF syndrome, despite a strong exogenous ovulatory signal, and the absence of any difference in peri-ovulatory hormonal parameters, indicates that the defect causing LUF resides in the follicle itself and/or hormonal changes during the follicular phase.

Prospective randomized study of clomiphene citrate and gonadotrophins versus goserelin and gonadotrophins for follicular stimulation in assisted reproduction.

We performed a prospective randomized study of goserelin, a long-acting gonadotrophin-releasing hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG) versus clomiphene citrate and HMG for follicular stimulation in assisted reproduction to investigate whether the use of this GnRHa provides a clear advantage in terms of pregnancy per treatment cycle in unselected patients, who entered a first trial of assisted reproduction. From a retrospective analysis comparing the two stimulation protocols, a relative increase of the pregnancy rate per cycle of 50% was anticipated. To detect this difference with a power of 90%, 300 patients had to be included. The main prognostic factors affecting the outcome of assisted reproduction were equally divided among the two groups by a minimization procedure. The pregnancy rates per cycle were significantly better in the goserelin/HMG group than in the clomiphene citrate/HMG group, both for all procedures of assisted reproduction combined (36.8 versus 24.5%; P < 0.02) and for the main procedure of in-vitro fertilization (IVF) (37.0 versus 23.5%; P < 0.02). Differences in pregnancy rates per oocyte retrieval and per embryo transfer were less pronounced (37.8 versus 30.8%; P = 0.40 and 44.4 versus 36.8%; not significant). On the other hand, stimulation with goserelin/HMG was associated with a higher number of ampoules of HMG (44.9 versus 9.9; P < 0.0001), a longer duration of stimulation (11.2 versus 8.7 days; P < 0.0001) and an incidence of ovarian stimulation of 4.5% (7/154) versus 0% in the clomiphene citrate/HMG group. Goserelin was well tolerated and proved to be very reliable as an adjunct of follicular stimulation in assisted reproduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Propofol anaesthesia for ultrasound guided oocyte retrieval: accumulation of the anaesthetic agent in follicular fluid.

Propofol (2,6-diisopropylphenol, Diprivan, ICI-Pharmaceuticals, Manchester, UK) is widely used either as an adjunct in general anaesthesia or as sole anaesthetic agent by the continuous intravenous route and intermittent bolus injections for minor surgical interventions. For several years, we have been using this kind of anaesthesia in transvaginal oocyte retrieval for in-vitro fertilization (IVF), allowing a completely painless puncture on an out-patient basis. From in-vitro studies on mouse oocytes, it appeared that propofol could be deleterious for fertilization in a dose- and time-dependent manner. We therefore investigated the concentrations of propofol in follicular fluid during oocyte retrieval in women. We measured propofol levels in serum and follicular fluid of nine patients at fixed intervals during ultrasound guided oocyte retrieval. Serum levels fluctuated randomly, due to interference from top-off doses of propofol. In follicular fluid, however, we found a steady increase of propofol levels, which was proportional to the total dose of propofol administered. These data indicate that propofol accumulates in follicular fluid. Although it seems unlikely that propofol as used in the present protocol exerts a clinically significant unfavourable effect on IVF, we suggest that the oocyte retrieval procedure should be kept as short as possible, in order to limit the accumulation of the anaesthetic in follicular fluid.