Iatrogenic multiple pregnancy: Lessons from the developed countries

Assisted reproduction technologies (ART) expose multiple ova to sperm, either in-vivo (by ovulation induction - Ol) or in-vitro (IVF). latrogenic - physician-made - multiple pregnancies (IMPs) are a consequence of an attempt to inerease pregnaney rates of costly therapies. A distinetion is made between unavoidable (most of Ol cases) and avoiclable (IVF) IMPs. Över the last decade, epidemic dimensions of IMPs have been observed: twins inereased 60-80% ancl higher-order multiples inereased 400-600% in most developed countries. The common etiology for this inerease in developecl countries is aclvanced maternal age at conception, characterized by reduced fecundity and inereased neecl for ART. ART is a particularly efficient treatmenl of mechanical infertility - the most common cause of infertility in developing countries.
Irrespective of debates such as therapy vs. prevention and governmental vs. private subsidizing, data show that most developing countries have ART centers. it is theretore important to leaın a lesson from llıe developed countries about the consecjuences ot this mode of conception.
The most serious complication of IMP.s is preterm birth of very and extremely low birth weight infants. The expecting mothers of twins and triplets have a 10% chance of delivering at least one infant who we-ighs <1500 and <1000 g, respectively. Preterm delivery and very and extremely low birth weight corre­late with neonatal mortality and with short- and long-term morbidity. For example, it is currently estima­ted that IMPs alone increase the cerebral palsy rate by 8%. In addition, although most IMPs are polyzy­gotic, it has been established that ART is associated with a 3 to 10 fold increased incidence of zygotic splitting. The consequences of monozygosity are higher frequencies of malformations, twin-twin trans­fusion, and complications of monoamnionicity. The expecting mother is at 4 to 6 times increased risk to develop serious hypertensive disorders, to experience preterm contractions, to be anemic, to sustain he­morrhage, and to undergo operative interventions. 
Because there are no practical methods to significantly reduce these complications, the only potential so­lution is to control the frequency of IMPs hy either avoicling Ol or hy transferring only a single high-qu­ality ernbıyo in each IVF cycle.