Introduction to IVF

The goal of IVF should be the recapitulation of normal human conception, with replacement of a single embryo, ideally with conception rates better than spontaneous human conception.

The latter goal has been reached in many of the best IVF programs, but at the cost of an epidemic of multiple gestations; 33% of pregnancies in women under age 40 were at least twin pregnancies.* These constitute the largest burden of IVF associated maternal morbidity and fetal/neonatal mortality and morbidity, and are an increasing public health burden. Appropriate histologic evaluations can help reduce morbidity and mortality by assessing for treatable conditions and predict previously undetected risk so modifications can be made in the second round of IVF protocol.

Histologic study of the tissues delivered from lost or complicated pregnancies conceived through IVF can identify subclinical infection, maternal vascular and "immune" pathologies which can be subsequently evaluated and treated to improve the outcome of the next pregnancy.

Improved understanding of the pathophysiology of euploid IVF loss/complications will:

• Allow for improved IVF preconceptional evaluation, and conceptional surveillance/intervention to reduce IVF singleton complication rate.
• Provide important psychological closure for patients. Late gestational complications are increasingly understood to have their genesis in pre- and peri-conception.

The insights gained may allow modifications of IVF methods and practice that may reduce multiple gestation rate while preserving high, healthy livebirth rates/cycle.

Background

An increasing proportion of births involve ART or IVF. Recently, it has been estimated that the health care costs for one IVF newborn from induction of pregnancy until the age of 7 days was 5.4-fold compared to other newborns. For example, 1998 Vital Statistics Records for the City of New York document a higher incidence of low birth weight infants born to older mothers than the youngest teenaged mothers. The public health costs of ART/IVF are mounting. Multiple gestation is by no means the only complication that can compromise pregnancies conceived with ART or IVF. The following are the significant pregnancy complications that can benefit from histologic evaluation.

Early loss: While as many 80% of early IVF losses (by 7-8 weeks) are random wrong chromosome number accidents, 20% are not. Given the emotional and real costs of IVF, such pregnancies deserve the best answer as to cause as can be provided. In general, non-chromosomal losses (losses with an apparently normal "developmental pattern book") are caused by the intrauterine environment. Pathologies include blood vessel/clotting and infectious/ "immune" problems (see below), which are potentially treatable in the next pregnancy.

Later complications: Currently, if you make it out of the IVF program and return to your OB, you may be considered a "success". Even if you have a late and lethal complication, there is no means for causal understanding to be either returned to the IVF program or incorporated into a proactive program of preconceptional evaluation and /or intervention.

The outcomes for singleton IVF pregnancies remains poorer than for spontaneous singleton conceptions, with increased risks of 2.6 (1.4-4.8) for perinatal mortality, 3.5 (2.2-5.7) for birth before 33 weeks of gestation, and 1.7 (1.5-1.9) for cesarean delivery in singleton pregnancies that resulted after in vitro fertilization. Others have reported the incidence of pregnancy-induced hypertension to be as high as 10%, preterm labor 21.5%, low birth weight in 30.5%, and intrauterine death in 2%. In Finland, every fourth child born to an IVF conception was still, preterm or weighed < 2500 g. The health care costs for one IVF newborn from induction of pregnancy until the age of 7 days was 5.4-fold compared to other newborns. The increased morbidity does not appear to be due to infection, possibly introduced by the procedure. Other explanations include abnormal maternal vascular and immune adaptations to pregnancy; costly IVIgG therapy, and off-label use of Viagra have been recently proposed to improve IVF success rates.

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