The use of fertility drugs, especially gonadotropins for ovulation induction, intrauterine insemination and in vitro fertilization have greatly increased the prevalence of multiple gestation. The rate of high order multiples (greater than twins) increased more than 100% between 1972 and 1990, approaching 80 per 100,000 live births by 1990. Because of the increased risk of prematurity and its associated problems, this has placed a large burden on both health care facilities and the couples coping, not only with prematurity, but also with caring for the children after multiple birth
The probability of prematurity (birth weight less than 2500 gms, five and one half pounds) increases with the number of fetuses, rising from about 5% in single births to 50% of twins. The average birth weight of twins is about 2300 gms. In higher order multiple births, 15% weigh 1000 gms or less compared with only 0.4% of single births, and 33% weighed less than 1500gm. The infant will usually reach a weight of 1500 grams at about 29 weeks gestation. This increase in the incidence of prematurity is associated with an increased risk of perinatal death and also a small but real risk for handicap of surviving infants. The risk of neonatal death is directly related to the weight at birth. The perinatal mortality of infants weighing between 600 and 699 grams is 800/ 1000, and 145/ 1000 at 1000 to 1299 gms. Infants who weigh over 2500 gm. have a loss rate of 6/ 1000. One large, recent study of 4004 infants born between 20 and 25 weeks showed that only 1185 (30%) had signs of life at birth, and of these, 843 were admitted to the neonatal intensive care nursery, the remainder having died in the delivery room. At 30 months of age, 49% of surviving infants were normal, 23% had severe disability and another 25% had less severe disability. A large study from Australia showed a prevalence of cerebral palsy in triplet births to be 28/1000 births, while the rates for twins and singletons was 7.3 and 1.6 respectively per thousand births. The evidence for mental impairment is less secure, but most studies show a small increase as the order of multiples increases. Another study from Japan showed that 3% of twins had some handicap, as compared with triplets at 8% and quadruplets at 11%. All the handicaps were not neurologic, and may not have been related to multiple pregnancies.
Maternal complications of pregnancy, while rarely life threatening, are much more common in multiple pregnancies. The risk of pregnancy induced hypertension (pre-eclampsia) is increased, and long term bed rest or hospitalization is frequently necessary. The latter is more common in high order multiples. Because of possible complications of labor and delivery, the incidence of cesarean section is also increased.
Causes of Multiple Gestation
A large portion of infertile women are not ovulating, and ovulation induction is required to achieve pregnancy. All the drugs used to induce ovulation are associated with an increased risk for multiples. Clomiphene citrate (clomid, serrophene) causes a risk of about 6%, but the great majority of these multiples are twins. It is quite unusual to have more than twins, but high order multiples may occur even with clomiphene citrate.
A minority of women do not respond to clomiphene, and more effective drugs are required. The next step in these non-responding women is the use of gonadotropins (GonalF, follistim, humagon etc). These drugs act directly on the ovaries and usually produce multiple ovulations. It is not possible to assure a woman that she will not have a multiple pregnancy when she is taking any of these drugs. The risk for multiples in women taking gonadotropins is about 30%, mostly twins, but these are the women most likely to have high order multiples. Controlled ovarian hyperstimulation with gonadotropins combined with intrauterine insemination is often used in women with open tubes, but also is associated with a high incidence of multiples.
In Vitro Fertilization (IVF)
In patients undergoing IVF, the pregnancy rate is related to the number of embryos placed in the uterus. In a woman less than 35 years of age, placing one embryo in the uterus would yield a pregnancy rate of around 25%, while placing three would result in a rate approaching 70%, but at the cost of a higher rate of multiples. The number of embryos replaced also depends on the patient’s age since there is a lower rate of implantation in older women. The apparent quality of the embryos must also be added to the equation, making the decision about the number of embryos to implant much more difficult than one of simple arithmetic. Ultimately, the patient makes the final decision. But our staff will be involved to try to assure that nothing is done to increase the risk greatly.
What to do if a high order multiple pregnancy occurs?
The choice of care is made, as always, by the patient. Some couples elect to carry quadruplets or triplets and accept the known risks. Others decide to do selective reduction and reduce the number to twins. Please read the section below for information on this procedure.
Selective or Fetal Reduction
Reduction usually is done between nine and ten weeks. The patient is sufficiently sedated that she feels no pain. A needle is inserted through the vagina into the fetal sac under ultrasound guidance, and a small amount of potassium chloride is injected. The reduced fetus is simply resorbed into the woman’s body. There is, of course, a small risk that the entire pregnancy will be lost, and the better centers report this risk at about 5-10%.
The staff at NCCRM understand that the decision to reduce is a very difficult and emotional one, and some women decide to carry a high order multiple pregnancy in spite of the risk. We will make every effort to provide as much support and help in decision making as possible.
To learn more or schedule a consultation:
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