Department of Obstetrics and Gynecology, Institute for the Health of Women and Children, Sahlgrenska University Hospital, East, 416 85 Göteborg, Sweden
1 To whom correspondence should be addressed. Email: wennerholm{at}swipnet.se
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Abstract |
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Key words: assisted reproduction/outcome/success rate
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Introduction |
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The lead debate article by Min et al. (2004) suggests BESST (Birth Emphasizing a Successful Singleton at Term) to be such a variable. Our comments on this suggestion are the following:
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(Live) Birth is appropriate |
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Successful is inappropiate |
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Singleton is appropriate |
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The main strategy for reducing the multiple birth rates would be to transfer fewer embryos per transfer and particularly increase the number of SET. Reported data after SET show satisfactory pregnancy or delivery rates (Gerris et al., 1999; Vilska et al., 1999
; Martikainen et al., 2001
; Tiitinen et al., 2001
, 2003
) at least for women with good prognosis after IVF.
Min et al. (2004) suggest including only stimulated IVF cycles, i.e. the results after frozenthawed cycles would be excluded. However, SET yields more impact on frozenthawed cycles, since more embryos are frozen. We suggest that results from frozen cycles should be reported in the same way as for stimulated cycles, i.e. singleton live births, but separately. In fact there are more arguments for transferring single embryos in thawed than in fresh cycles since embryos can be frozen and thawed one by one without further losses.
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(Only) Term singleton is inappropriate |
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Preterm birth is related to gestational age and is defined by the World Health Organization as birth before 37 completed weeks or 259 days of gestation.
Today there is a great deal of evidence of an increased preterm rate for IVF singletons compared with naturally conceived singletons (Helmerhorst et al., 2004; Jackson et al., 2004
). In a systematic review, Helmerhorst et al. found, for singletons compared with matched controls, a relative risk (RR) of 3.27 (95% CI 2.035.28) for very preterm birth (<32 weeks) and 2.04 (95% CI 1.802.32) for preterm birth (<37 weeks) in pregnancies after assisted conception. Results of the non-matched studies were similar. In a recent meta-analysis including 15 studies comprising 12 283 IVF and 1.9 x 106 spontaneously conceived singletons, an odds ratio of 2.0 (95% CI 1.72.2) for preterm birth was found (Jackson et al., 2004
). To our knowledge, no study has so far compared the outcome for SET singletons resulting from mild stimulation protocols with IVF singletons in general.
Women with assisted pregnancies differ from other women in many characteristics that influence outcome, including age, parity and socioeconomic status and the underlying subfertility. In the population-based Swedish registry study we found a risk ratio of 2.04 (1.852.26) for preterm birth. After stratification for maternal age, parity and duration of infertility the RR decreased to 1.48 (95% CI 1.301.68) (Bergh et al., 1999).
The reported incidence of preterm birth in the international literature varies from 6 to 15% of all deliveries depending on the geographical and demographic features of the population studied (Slattery and Morrison, 2002). There has been a tendency towards higher reported rates in recent years which has been attributed to several factors including increased obstetric interventions, use of assisted reproduction techniques and increased rate of multiple pregnancies.
Preterm birth may be categorized according to three different modes of clinical presentation: medically indicated (iatrogenic) preterm birth, preterm pre-labour rupture of the membranes (PPROM) and preterm labour (PTL) (Savitz et al., 1991). PTL and PPROM are often combined and called spontaneous (idiopathic) preterm birth. The aetiology of preterm birth is multifactorial. Those risk factors found in association with preterm birth can be divided into three groups: those associated with factors related to sociobiological variables (maternal age and parity, marital status, race and ethnicity, cigarette smoking, environmental stress, work, nutrition, maternal size, interpregnancy interval, alcohol, coffee and substance abuse), past obstetric history (previous preterm birth, previous abortion) and complications of the current pregnancy (elective preterm birth, multiple gestation, insufficient antenatal care, male sex, uncertain gestation, congenital malformation).
In spite of increasing knowledge about epidemiological risk factors, research efforts to date have failed to result in any improvement in prediction and prevention of preterm delivery.
Owing to all the above reasons, the differences between populations in terms of ethnicity and sociodemographic factors make comparisons in preterm birth rate complicated (Savitz et al., 1991). The preterm birth rate for black women is almost twice that for white women of comparable age in the USA (McGrady et al., 1992
; Schieve and Handler, 1996
; Ananth et al., 2001
).
Thus preterm birth is a heterogeneous perinatal problem both in terms of aetiology and numerous associated risk factors, and more important, the rate of preterm birth in singletons cannot be influenced to any huge extent by the individual IVF clinics but is mainly a result of the specific IVF population being treated.
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Exclusion of singletons with a congenital malformation is inappropriate |
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Preferably, registration of congenital malformations in an assisted reproduction population should include: a prospective surveillance for major anomalies, defined as those causing death, severe disability or requiring surgery. Prospective surveillance should ideally include collection of information at the time pregnancy is diagnosed, surveillance during pregnancy to exclude teratogenic influences, and a systematic neonatal anomaly examination. Today, this goal is impossible to achieve worldwide.
In summary, we propose that singleton live birth per cycle initiated is the most appropriate main outcome and that the preterm birth rate be reported separately as a secondary outcome.
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References |
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Ananth CV, Misra DP, Demissie K and Smulian JC (2001) Rates of preterm delivery among black women and white women in the United States over two decades: an age-period-cohort analysis. Am J Epidemiol 154, 657665.
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Gerris J, De Neubourg D, Mangelschots K, Van Royen E, Van de Meerssche M and Valkenburg M (1999) Prevention of twin pregnancy after in-vitro fertilization or intracytoplasmic sperm injection based on strict embryo criteria: a prospective randomized clinical trial. Hum Reprod 14, 25812587.
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Helmerhorst FM, Perquin DA, Donker D and Keirse MJ (2004) Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies. Br Med J 328, 261.
Jackson RA, Gibson KA, Wu YW and Croughan MS (2004) Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis. Obstet Gynecol 103, 551563.[Medline]
Martikainen H, Tiitinen A, Tomas C, Tapanainen J, Orava M, Tuomivaara L, Vilska S, Hyden-Granskog C and Hovatta O (2001) One versus two embryo transfer after IVF and ICSI: a randomized study. Hum Reprod 16, 19001903.
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Slattery MM and Morrison JJ (2002) Preterm delivery. Lancet 360, 14891497.[CrossRef][Medline]
Tiitinen A, Halttunen M, Harkki P, Vuoristo P and Hyden-Granskog C (2001) Elective single embryo transfer: the value of cryopreservation. Hum Reprod 16, 11401144.
Tiitinen A, Unkila-Kallio L, Halttunen M and Hyden-Granskog C (2003) Impact of elective single embryo transfer on the twin pregnancy rate. Hum Reprod 18, 14491453.
Vilska S, Tiitinen A, Hyden-Granskog C and Hovatta O (1999) Elective transfer of one embryo results in an acceptable pregnancy rate and eliminates the risk of multiple birth. Hum Reprod 14, 23922395.
World Health Organization (1977) Manual of the International Statistical Classification of Diseases, Injuries and Causes of Death, Vol 1. WHO, Geneva.
Submitted on May 4, 2004; accepted on June 3, 2004.