ReviewMultiple pregnancies following assisted reproductive technologies – A happy consequence or double trouble?
Introduction
The incidence of multiple births has risen steadily over the last 30 years, mainly due to the increasing use of assisted reproduction technologies (ART) and the increase in average maternal age at conception. ART is defined as any procedure that entails the handling of both eggs and sperm, or of embryos, for the purpose of establishing a pregnancy [gamete intrafallopian transfer (GIFT); in-vitro fertilisation (IVF); intracytoplasmatic sperm injection (ICSI)] [1]. In 2009, 16 women per 1000 had multiple births accounting for 3% of all live births [2]. The current rate of multiple births in ART is 24% [2]. Although multiple pregnancy is associated with adverse pregnancy outcomes, a significant proportion of infertility patients considers multiple pregnancy to be an ideal treatment outcome [3].
Multiple pregnancy is associated with significantly higher risk than singleton pregnancies for both the mother and the babies. Maternal antepartum, intrapartum and postpartum complications are more frequent, as are perinatal sequelae. Multiple pregnancies therefore require more monitoring and increased contact with healthcare professionals, resulting in an increased financial burden to the National Health Service (NHS). Indeed the maternal care for twin pregnancies appears to be twice as costly as the care for mothers with singleton pregnancy, because of the increased caesarean section rate and the need for specialist obstetric care [4]. Increased rates of prematurity will increase costs of caring for the neonate, as well as the costs of prematurity-induced lifelong disability. This paper aims to review the maternal and perinatal consequences of multiple pregnancy. The outcome of ART twins versus naturally conceived twins is also discussed. Current best practice advice on minimising the risk of multiple pregnancy in ART will also be outlined.
Section snippets
Maternal consequences of multiple pregnancy
Multiple pregnancy is associated with increased maternal morbidity compared with singleton pregnancy [2]. There is good evidence that the incidence of pregnancy-induced hypertension is increased with multiple pregnancy. A cohort study reporting on 34,374 pregnancies with one to four fetuses published in 2005 found the incidence of pregnancy-related hypertensive disease to be 6.5% for singletons versus 12.7–19.7% for multifetal pregnancies (P < 0.001) [5]. Sibai et al. undertook a prospective
Perinatal consequences of multiple pregnancies
The most frequently reported perinatal consequence of multiple pregnancy is the risk of preterm labour. Approximately 94% of multiple gestations are twins [16]. Recent US national statistics published in 2011 found that in 137,217 twin pregnancies 58.8% delivered preterm (<37 weeks) and 11.4% were delivered very preterm (<32 weeks of gestation) [17]. In the same report of 5095 triplet pregnancies, 94.4% delivered preterm (<37 weeks of gestation) and 36.8% delivered very preterm (<32 weeks of
Outcomes of ART versus naturally conceived twins
The number of women having ART (IVF/ICSI) pregnancies is increasing worldwide, and the rate of multiple pregnancy is higher with ART. It has been suggested that obstetric outcomes in pregnancies after IVF/ICSI are poorer when compared with those after natural conception, and this affects the counselling of patients and the guidance of clinical practice [28]. Apart from the overall complications of a twin pregnancy per se, ART twin pregnancies usually have additional obstetric risk factors
Strategies for minimising risk
Due to the increased perinatal and maternal risks of multiple pregnancy it is paramount to identify ways of preventing iatrogenic multiple pregnancies. Multiple pregnancy remains the single biggest risk to the health and welfare of children born after IVF [42]. The National Institute for Health and Care Excellence (NICE) fertility guideline published in February 2013, aimed at maximising outcome and minimising risk, provides an authoritative and carefully researched body of evidence [43]. A
Conclusion
Multiple pregnancy rates in the context of ART remain high. Twins and higher-order multiples carry increased maternal and perinatal risks as well as an increased cost to the NHS. Although most of the current research states that obstetric outcomes of ART twins are similar to naturally conceived twins, twin pregnancy per se significantly increases the risk of obstetric complications and perinatal mortality and morbidity. For the above reasons centres performing ART should strive to prevent
Conflict of interest statement
None declared.
Funding sources
None.
References (62)
- et al.
Hypertensive disorders in twin versus singleton gestations
Am J Obstet Gynecol
(2000) - et al.
Maternal physiology and complications of multiple pregnancy
Semin Perinatal
(2005) - et al.
Gestational diabetes mellitus: metabolic and blood glucose parameters in singleton versus twin pregnancies
Am J Obstet Gynaecol
(1999) - et al.
Venous thromboembolism in pregnancy and the puerperium: incidence and additional risk factors from a London perinatal database
Br J Obstet Gynaecol
(2001) - et al.
Seventy-one quadruplet pregnancies: management and outcome
Am J Obstet Gynecol
(1990) High-order multiple gestations
Semin Perinatol
(2005)- et al.
Follow-up of twins: health, behaviour, speech, language outcomes and implications for parents
Early Hum Dev
(2006) - et al.
Perinatal outcomes of in vitro fertilization twins: a systematic review and meta-analyses
Am J Obstet Gynecol
(2005) - et al.
Increased risk of preterm birth in singleton pregnancies resulting from in vitro fertilization–embryo transfer or gamete intrafallopian transfer: a meta-analysis
Fertil Steril
(2004) - et al.
Perinatal and neonatal outcomes in multiple gestations: assisted reproduction versus spontaneous conception
Am J Obstet Gynecol
(1998)
Perinatal outcome of twin pregnancies obtained after in vitro fertilization: comparison with twin pregnancies obtained spontaneously or after ovarian stimulation
Fertil Steril
The likelihood of live birth and multiple birth after single versus double embryo transfer at the cleavage stage: a systematic review and meta-analysis
Fertil Steril
Outcome and feasibility of elective single embryo transfer (eSET) policy for the first and second IVF/ICSI attempts
Eur J Obstet Gynecol Reprod Biol
Impact of a restriction in the number of embryo transferred on the multiple pregnancy rate
Eur J Obstet Gynaecol Reprod Biol
Fetal reduction
Semin Perinatol
Selective reduction and termination of multiple pregnancies
Semin Fetal Neonat Med
Improvement in outcomes of multifetal pregnancy reduction with increased experience
Am J Obstet Gynaecol
Neonatal outcomes in triplet pregnancies: assisted reproduction versus spontaneous conception
J Perinat Med
Clinical guideline 129. Multiple pregnancy – the management of twin and triplet pregnancies in the antenatal period
The desire for multiple pregnancy in male and female infertility patients
Hum Reprod
Costs of NHS maternity care for women with multiple pregnancy compared with high-risk and low-risk singleton pregnancy
Br J Obstet Gynaecol
The effect of fetal number on the development of hypertensive conditions of pregnancy
Obstet Gynecol
Risk factors for pre-eclampsia at antenatal booking: a systematic review of controlled studies
BMJ
One consequence of infertility treatment: multifetal pregnancy
Am J Maternal/Child Nurs
Multiple pregnancy
BMJ
Risk for developing gestational diabetes in women with twin pregnancies
J Maternal–Fetal Neonat Med
Clinical guideline 132. Caesarean section
Maternal morbidity and perinatal outcome with twin pregnancy
J Ayub Coll Abbottabad
Births: final data for 2009
Natl Vital Stat Rep
Perinatal Mortality 2007: United Kingdom
Multiple pregnancies and birth: considering the risks
Cited by (46)
Utility of cervical pessary in the prevention of preterm birth in triplet pregnancies: A single-center observational retrospective study of 165 triplet pregnancies
2024, European Journal of Obstetrics and Gynecology and Reproductive BiologyComparison of maternal, fetal, obstetric and neonatal outcomes for 234 triplet pregnancies conceived in vivo versus IVF and ICSI conceptions
2024, Reproductive BioMedicine OnlineCardiovascular mortality risk a decade after twin and singleton pregnancies complicated by hypertensive disorders of pregnancy
2022, Pregnancy HypertensionCitation Excerpt :In other words, the pregnancy acts as a “stress test” for the already susceptible maternal cardiovascular system [17]. Compared to singleton pregnancies, the incidence of PE in twin pregnancies is two to three times higher [21–23]. This might be explained by a greater placental mass in twin pregnancies, posing greater stress to the maternal cardiovascular system [24–28].
Obstetric and perinatal complications in infertile women who become pregnant
2021, Revista Medica Clinica Las CondesSecond-generation preimplantation genetic testing for aneuploidy in assisted reproduction: a SWOT analysis
2019, Reproductive BioMedicine OnlineClinical outcomes of multifetal pregnancy reduction in trichorionic and dichorionic triplet pregnancies: A retrospective observational study
2019, Taiwanese Journal of Obstetrics and GynecologyCitation Excerpt :Besides, multiple embryos transferring in ART treatment cycles are applied to maximize pregnancy rate [3–5]. Meanwhile, the complications and risks for both women and infants in multifetal pregnancies are well recognized, including the increased rates of abortion, preterm birth, cesarean section, and postpartum hemorrhage [6]. In addition, neonatal morbidity and mortality rates may also increase due to malformation and intrauterine growth retardation in multifetal pregnancy [7].