European Journal of Obstetrics & Gynecology and Reproductive Biology
Impact of a restriction in the number of embryos transferred on the multiple pregnancy rate
Introduction
The cost of an in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment has always been an important consideration for patients and doctors. This expensive treatment was and still is in many countries at the expense of the patients. Apart from the cost of the treatment itself, it was also realised that multiple pregnancies and high order multiple pregnancies particularly were a source of enormous expenses for insurance and social security systems.
In the 1990s, there had been a spectacular increase in admissions in neonatal intensive care units of children from multiple pregnancies which originated from assisted reproduction technologies (ART). Therefore, if one wanted to decrease the complications for children born after ART, the reduction of multiple pregnancies through the introduction of single embryo transfer (SET) was the only and obvious solution. When considering single embryo transfer, two important aspects had to be taken into account. On one hand will a decrease in complications related to preterm delivery in multiple pregnancies lead to an important decrease in the cost originating from the admission and treatment of children of multiple pregnancies. On the other hand would a significant drop in the pregnancy rate after single embryo transfer render this policy unacceptable for both patients and doctors because a low pregnancy rate would lead to an important increase in the number of treatment cycles for the patient and would in itself substantially increase the cost of IVF/ICSI treatment. We have previously shown that the introduction of single embryo transfer is acceptable to the patients [1] and halves the twinning rate of the whole program [2].
The importance of the financial impact was demonstrated in a study on insurance coverage and outcome of in vitro fertilization [3]. These authors showed that state-mandated insurance coverage for IVF services was associated with increased utilization of these services but with decreases in the number of embryos transferred per cycle, the percentage of cycles resulting in pregnancy and the percentage of pregnancies with three or more fetuses. The Swedish public health care system in 2002 had imposed SET for all IVF treatments offered by public health care, except for special circumstances were double embryo transfer (DET) was allowed. On January 1, 2003 a general decree was released that all IVF treatments should be SET with the exception of DET when the risk for twinning was considered low (>39 years, poor embryo quality, ≥3 previously failed cycles). Saldeen and Sundström [4] showed that the legislation had no negative consequences for the couples: there was no difference in clinical pregnancy rates before and after the introduction of SET by legislation but the twinning rate was significantly lower. We performed a real-life prospective health economic study that compared elective single embryo transfer versus two-embryo transfer in the first IVF/ICSI cycle for maternal, neonatal and total costs. The conclusion of this study was that transfer of a single top quality embryo is equally effective as but substantially cheaper than double embryo transfer in women <38 years of age in their first IVF/ICSI cycle [5].
Many of these aspects have been taken into consideration by the Belgian government when considering reimbursement of the laboratory costs for IVF/ICSI. It was calculated that with a substantial decrease (50%) in the number of multiple pregnancies after IVF an important amount of money could be saved from the treatment of preterm birth and its sequelae. With the saving of these costs, the reimbursement of 7000 IVF/ICSI cycles could be paid [6]. Therefore, reimbursement of the laboratory costs for IVF/ICSI is linked to a decree which states the maximal number of embryos for transfer depending on the age of the woman and the rank of the cycle (Table 1) [7]. It will be interesting to follow the effect of the implementation of the law since the introduction on July 1, 2003 for the whole IVF/ICSI population in Belgium both on the outcome of IVF/ICSI in terms of pregnancy rate as well as the impact on the twinning rate. Data from the Belgian Registry for 2002 (Belrap) [8] which is the year prior to implementation of the law show that only 14.5% of transfers were single embryo transfers resulting in a multiple pregnancy rate of 24.4%. Both patients and doctors are obliged to adhere to the embryo transfer strategy as stated in the law as reimbursement of the laboratory costs is coupled to a correct implementation of the transfer strategy for the whole IVF/ICSI program and not for individual cycles. Therefore, a very high rate of adherence is expected.
In the meantime, we calculated the effect on our program in the first year since the introduction of the law (July 1, 2003–June 30, 2004).
Section snippets
Materials and methods
Patients were treated with the long gonadotropin releasing hormone (GnRH) agonist desensitization protocol, starting in the midluteal phase with 6 × 100 μg of buserelin (Suprefact®, Aventis Pharma, Germany) intranasal for a period of three weeks. Thereafter gonadotropin stimulation (Menopur®, Ferring, Copenhagen, Denmark; Gonal-F®, Serono, Geneva, Switzerland and Puregon®, Organon, Oss, The Netherlands) was initiated. When at least three mature follicles with a diameter of 18 mm were present 10.000
Results
During the first year since reimbursement (July 1, 2003–June 30, 2004) there were 448 cycles leading to ovum pick-up and 409 cycles (91.3%) were reimbursed. There were 207 (46.2%) IVF cycles and 241 (53.8%) ICSI cycles. The indication for IVF/ICSI was male subfertility 242/448 (54%), female pathology 104/448 (23.2%), mixed male and female pathology 38/448 (8.5%) and idiopathic infertility in 64/448 (14.3%) of cases. A mean of 10.6 ova were retrieved per ovum pick-up. The fertilization rate was
Comment
These data show that the patient in the Belgian social security system with full reimbursement of all laboratory costs related to IVF/ICSI and partial reimbursement of consultation, ultrasonography, endocrine assays, ovum pick up and embryo transfer as well as admission in the hospital and necessary drugs can be offered a pregnancy rate of 42.2% and ongoing pregnancy rate of 29.7%. One need to take into account that since the introduction of the reimbursement of the IVF/ICSI laboratory costs
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Cited by (19)
Multiple pregnancies following assisted reproductive technologies - A happy consequence or double trouble?
2014, Seminars in Fetal and Neonatal MedicineCitation Excerpt :It was concluded in this review that elective single embryo transfer should be the default for reducing the risk of preterm birth and multiple pregnancy. These results were in corroboration with previous reviews of the literature [42,47,51]. A cost-effectiveness analysis of 661 women undergoing IVF found single embryo transfer to be superior to double embryo transfer, when number of deliveries with at least one live-born child, incremental cost-effectiveness ratio, and maternal and paediatric complications were taken into consideration [52].
Anti-Müllerian hormone as an independent predictor of twin versus singleton pregnancy in fresh cycles
2013, Reproductive BioMedicine OnlineCitation Excerpt :Maternal complications include haemorrhage, pregnancy-induced hypertension and anaemia, as well as maternal mortality (Martin et al., 2007). In an effort to minimize the twin pregnancy rate, a policy of elective single-embryo transfer (eSET) has been adapted in many countries for specified patient groups (Cutting et al., 2008; De Neubourg et al., 2006; Nyboe Andersen et al., 2009). The introduction of the eSET policy has been shown to lead to a dramatic reduction in multiple pregnancies and improvement in both maternal and neonatal outcomes, although at the cost of slightly reduced pregnancy rates (Kallen et al., 2010; Luke et al., 2010).
Cumulative live-birth delivery after IVF/ICSI since the progressive introduction of single-embryo transfer
2010, Reproductive BioMedicine OnlineCitation Excerpt :In the study centre, SET was also advised in consecutive cycles and extended to patients up to 38 years of age (De Neubourg et al., 2006). From 1 July 2003, the Belgian government linked reimbursement of the laboratory costs of six IVF/ICSI cycles to a restriction of the number of embryos transferred, related to age of the patient and rank of the cycle (De Neubourg et al., 2006; Ombelet et al., 2005). From the moment the number of embryos for transfer was legally restricted, the multiple pregnancy rate decreased from 24.4% to 13.4% for all IVF/ICSI patients in Belgium (Belrap, 2002, 2006).
Aromatase inhibitors in ovarian stimulatio for IVF/ICSI: A pilot study
2006, Reproductive BioMedicine Online