There has been a lot of concern regarding the association of increased rate of fetal and maternal complications associated with IVF. The probable maternal complications with IVF include: complications occurring during pregnancy (multiple pregnancy, preterm delivery, increased rate of caesarian section etc) and complications related to the procedure (ectopic pregnancy and ovarian hyperstimulation syndrome). The probable fetal complications associated with IVF include: congenital malformations, multiple pregnancy, prematurity and low birth weight babies.
It has been hypothesized by Anthony, et al.(2002) that IVF could be associated with an increased incidence of congenital abnormalities in the baby. This is so since in this procedure ovulation, fertilization and early embryonic development may occur under influence of medicines and in an artificial environment. The increased rate of chromosomal aberrations in the resulting zygote could also be due to relatively advanced age of the infertile couple and fertilization of an aged ovum by abnormal sperms due to the fact that a large number of IVF patients show some abnormality of male factor (Anthony, et al.2002).
Besides these possible complications, IVF is a very costly procedure and is associated with high health care costs (Van Voorhis, et al. 1997). Fetal complications Recent reports of congenital abnormalities (neural tube defects, gastro-intestinal and urogenital problems) in children who were conceived with assisted reproductive technologies has led to the initiation of prospective and retrospective follow-up studies in these children in order to evaluate the safety of these techniques.
In 2002, Anthony et al.observed an increase in rate of cardiovascular and some other specific minor congenital malformations (single umbilical artery, inguinal hernia, club foot etc) in children conceived after in vitro fertilization, in their study. However this increase was attributed to difference in maternal characteristics (the mothers who underwent IVF procedure were of advanced age and lower parity as compared to mothers who conceived naturally) and not due to any aspect of in vitro fertilization procedure.
Pregnancies associated with assisted reproductive technologies (ART) are more likely to result in multiple births as compared to spontaneously conceived pregnancies (Wright, Schieve, Reynolds, & Jeng. 2003). Wright, et al also reported that the percentage of multiple births in infants born through ART in the year 2000 in the US was overall 53% (44% twin pregnancies and 9% triplet pregnancies and other higher order multiples).
[This report was based on ART surveillance data provided to CDC’s National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Reproductive Health, regarding procedures performed in 2000].
This rate was substantially higher than that of general U. S population during the same period. With the increasing use of ART, ART-related multiple births are becoming increasingly important public health problem nationally and in many states of US. This is so as multiple births are associated with increased risk for both mothers and infants. Triplet and higher-order multiple births are at greater risk than singleton births to be preterm (less than or equal to 37 completed weeks’ gestation), low birth weight (LBW) (less than or equal to2.5 kg), or very low birth weight (i. e. , <1. 5 kg), resulting in higher infant morbidity and mortality (Wright, et al. 2003).
In addition, Low birth weight babies are at an increased risk of long term disabilities and death. Preterm and LBW infants often require costly neonatal care and long-term developmental follow-up, resulting in total increased cost of care. Many maternal complications have also been found to be associated with multiple pregnancies.
Daniel, et al.(2000) reported a significantly higher incidence of pregnancy-induced hypertension, uterine bleeding, premature contractions, intrauterine growth retardation, fetal death, discordance, and cesarean section in women with twin pregnancies who had conceived after ART in comparison with women who had normally conceived. Thus it can be concluded that ART-conceived twin pregnancies are at greater risk than non-ART-conceived ones for pregnancy complications and adverse perinatal outcome.
Daniel, et al.(2000) also revealed that number of embryos transferred per IVF cycle was a risk factor for multiple-birth delivery, but the magnitude of the risk for multiple gestation varied according to patient age. The increased risk of low birth weight associated with the use of assisted reproductive technology has been largely attributed to the higher rate of multiple gestations associated with such technology. It is not clear however, whether singleton infants conceived with the use of assisted reproductive technology may also have a higher risk of low birth weight as compared to those who are conceived spontaneously.
Schieve, et al (2002) in their study estimated that the use of assisted reproductive technology accounted for 3. 5 % of the infants with low birth weight and 4. 3 % of the infants with very low birth weight. They largely contributed this increase to the increased number of infants from multiple births who were conceived with assisted reproductive technology. However, the increased rates of low birth weight among singletons conceived with assisted reproductive technology also played a small part . 0. 6 % of low-birth-weight singletons were conceived with assisted reproductive technology, as compared with the 0.
2 % low birth weight singletons in normal pregnancy. The study conducted by Schieve, et al (2002) suggests that the increased risk of low birth weight in singleton infants born at term who were conceived with assisted reproductive technology may be directly related to such treatments for infertility. Schieve, et al (2002) also observed an interesting thing in their study: twins conceived with assisted reproductive technology and born at term were not found to be at a higher risk of low birth weight as compared to twins born in the general population.
They explained it by saying that it is possible that the additional risk associated with the use of assisted reproductive technology is negligible in twin pregnancies, which are already at high risk for low birth weight. However the mechanisms underlying the association between the use of assisted reproductive technology and low birth weight among infants born at term remain unclear and warrant further research.
Maternal complications The use of assisted reproductive technology has been linked to an increased rate of maternal complications like gestational diabetes mellitus, pregnancy-induced hypertension, complications related to twin pregnancies and greater risk for delivery by cesarean section (Maman, Lunenfeld, Levy, Vardi and Potashnik 1998). Assisted reproductive technologies also pose a risk for potentially fatal complications like ectopic pregnancy and ovulation hyperstimulation syndrome (OHSS).
Ovarian hyperstimulation syndrome (OHSS) is a rare, iatrogenic and potentially life Threatening complication that can be encountered in the women who are given ovulation inducing agents (like clomipine citrate, gonadotropins etc) as a step of in vitro fertilization procedure (Delvigne, & Rozenberg 2003). The incidence of OHSS varies from 0. 1% to 4% in patients receiving ovulation induction treatments but this low incidence has been increasing worldwide due to the expansion of infertility treatments (Delvigne, & Rozenberg 2003).
Development of IVF and of techniques such as cryopreservation of excessive embryos has led to an increasing use of ovulation inducing agents in order to obtain sufficient numbers of oocytes and embryos. The syndrome is characterized by massive accumulation of extracellular protein-rich fluid (leading to massive ascites, pleural effusion and pericardial effusion), profound intravascular volume depletion and hemoconcentration (Delvigne, & Rozenberg. 2003).
Other abnormalities that may accompany the syndrome include: electrolytic imbalance, neurohormonal and haemodynamic changes, pulmonary manifestations, liver dysfunction, hypoglobulinaemia, febrile morbidity, thromboembolic phenomena, neurological manifestations, adnexal torsion, a state of hypercoagulability, thromboembolic phenomena, adult respiratory distress syndrome, and death. However, the syndrome’s pathophysiology is not completely understood, and no specific therapy or prevention strategy is available at present.
According to Delvigne, & Rozenberg (2003) the cascade of events that lead to OHSS are initiated by certain systemic and ovarian biosynthetic cytokines and vasoactive and angiogenic factors that are produced in excess during induction of ovulation. Ectopic pregnancy or extrauterine pregnancy is an important complication of IVF which can have devastating consequences for the woman and can even prove fatal. Clayton, et al (2006) reported an ectopic pregnancy rate of 2. 1% in patients undergoing ART.
Clayton, et al (2006) also observed that risk of ectopic pregnancy among ART pregnancies varied depending on the type of ART procedure performed. In comparison with the ectopic rate of 2. 2% among pregnancies conceived with in vitro fertilization, the ectopic rate was significantly increased when zygote intrafallopian transfer (ZIFT) was used (3. 6%). The risk for ectopic pregnancy was also increased among women with tubal factor infertility. Increased health care costs Assisted reproductive techniques are associated with increased health care costs as
compared to other methods used for treatment of infertility. In a cohort study conducted by Van Voorhis, et al (1997) cost-effectiveness of various infertility treatments was determined. . They found that intrauterine insemination (IUI), combination of clomiphine citrate and intrauterine insemination (CC-IUI) and a combination of human menopausal gonadotropin (hMG) and intrauterine insemination (hMG-IUI) had a similar cost per delivery varying between $7,800 and $10,300. All of these methods were more cost-effective than ART, which had a cost per delivery of $37,000.
Assisted reproductive technique in women with blocked fallopian tubes was more cost-effective than tubal surgery performed by laparotomy, which had a cost per delivery of $76,000. Thus Van Voorhis, et al. (1997) reached a conclusion that less costly procedures like IUI, CC-IUI, hMG-IUI should be used be tried first in a woman with open fallopian tubes before trying out ART. For women with blocked fallopian tubes, IVF appears to be the best treatment from a cost-effectiveness standpoint.