Multiple Gestation

By far the greatest risk of in vitro fertilization today is multiple gestations. Multiple gestations ultimately depend on the number of embryos transferred; thus the risk is primarily iatrogenic. In women under the age of 35 years, twin pregnancy rates can be as high as 40% when two high quality embryos are transferred. In general, assisted reproductive technology increases the risk of multiple pregnancies by 10-fold above baseline (35% vs. 3% in the general population). It is true that the success rates in in vitro fertilization improve with a greater number of embryos transferred, but only to a certain point. Beyond this point, only the risk of multiple pregnancy increases. Another risk factor for multiple pregnancy is maternal age. Younger women tend to be at higher risk of multiple pregnancy when more than one embryo is replaced. The problem with multiple gestations lies in the risks during pregnancy to both the fetuses and the mother. A greater risk of preterm delivery is the most significant consequence of multiple gestation. Multiples also have a higher risk of congenital malformations, and monochorionic twins are at increased risk of twin-twin transfusion syndrome. This can cause significant morbidity or even mortality for one or both fetuses. There also appears to be an increased risk of cerebral palsy in multiple pregnancies compared to singletons. Lastly, there appears to be a slightly higher risk of monozygotic twinning following assisted reproductive technology compared to the general population. The mechanism of this is not well understood but is believed to be due to trauma to the zona pellucida with herniation of the blastocyst.

Parents with multiple gestations, especially high-order multiples (three or more), frequently must face the decision of multifetal pregnancy reduction. This can be emotionally traumatic for couples that have struggled with the inability to become pregnant for long periods and the psychological morbidity is well documented.

There are obstetrical risks for the mother associated with a multiple pregnancy as well. Women carrying multiple gestations, especially higher order gestations, are at increased risk of hypertension, preeclampsia, and preterm labor. They are more frequently treated with prolonged bed rest and operative delivery compared to women carrying singleton pregnancies.

Ovarian Hyperstimulation Syndrome (OHSS)

Ovarian hyperstimulation syndrome can occur when a woman over-responds to high-dose gonadotropin stimulation. Risk increases with larger numbers of developing follicles and greater number of eggs retrieved. Youngerwomen also tend to be at higher risk of ovarian hyperstimulation syndrome compared to older women. Pregnancy will also increase the risk of ovarian hyperstimulation syndrome as well as the severity and duration of it. Although the pathogenesis is not well defined, ovarian hyperstimulation syndrome appears to be dependent on human chorionic gonadotropin as well as angiogenic factors. Most women who present with ovarian hyperstimulation syndrome show signs of increasing abdominal distention, ascites, nausea, vomiting, decreased urine output, hypercoagulability, and electrolyte imbalance. If symptoms are severe, there is also an increased risk of deep venous thrombosis. Ovarian hyperstimulation syndrome can be classified as mild, moderate, or severe; however it is uncommon to see severe ovarian hyperstimulation syndrome requiring hospitalization. Most of the time, women with ovarian hyperstimulation syndrome can be treated symptomatically with expectant management. Occasionally, women will need to undergo a paracentesis to remove excess abdominal fluid (often done transvaginally under ultrasound guidance). This procedure frequently results in immediate improvement in patient discomfort and symptoms.

Ectopic Pregnancy

Pregnancies implanted outside the uterus are much more common in ART-conceived cycles than the general population (5% vs. 1-2%). The risk is higher in women with tubal disease or a prior history of ectopic pregnancy. The mechanism is not well understood but is likely due to natural migration of the embryo into the tube after transfer or inadvertent direct tubal embryo transfer. The risk of heterotopic pregnancy in the general population is very rare (1 in 10,000), but the risk is increased substantially in women who conceive after in vitro fertilization or ovulation induction.

Other Risks

There is a small risk of internal bleeding, vascular injury, and infection from oocyte retrievals. Bleeding from the vaginal wall is fairly common after oocyte retrieval and usually stops spontaneously after the procedure or with the application of pressure. Severe pelvic infection is rare (<1%), and prophylactic antibiotics are usually not needed unless the patient is at high risk for pelvic inflammatory disease.

Fetal Risks

There are currently a number of studies suggesting an increased risk of birth defects in babies conceived after vitro fertilization. In cases where in vitro fertilization and intracytoplasmic sperm injection has been performed for a severe male factor, a several-fold increase was found in spontaneous anomalies of the sex and autosomal chromosomes and an increased risk of inherited chromosomal defects. Another study has suggested an increased incidence, albeit small, of Beckwith-Wiedemann and Angelman syndromes, which are complex disorders of growth and development associated with aberrant imprinting at chromosome 11q15-5 and the UBEA3 gene locus on chromosome 15q11-13, respectively. These disorders are the result of genetic alterations affecting the regulatory mechanism of genes, rather than DNA sequence (imprinting). Finally, there is some evidence to indicate that the risk of birth defects (heart, muscle or skeletal) is slightly higher in babies conceived through in vitro fertilization as compared to babies conceived naturally. What remains to be determined is whether it is the in vitro fertilization procedure itself or whether the increased risk is due to the infertility population undergoing treatment. Certainly ongoing research is required to better investigate the true fetal risks associated with assisted reproductive technology outcome. Appropriate counseling of couples regarding the potential for risk associated with assisted reproductive technology is recommenced.

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