Complication of IVF

IVF is basically a safe procedure. However, as with any surgical procedure, a few patients will experience side effects and complications. As with any medical or surgical procedure, a few patients undergoing IVF treatment will experience side effects and complications. The most common complications associated with IVF treatment are the failure of treatment, problems experienced as a consequence of ovarian stimulation, the risk of multiple pregnancy, the risks associated with egg collection and the possibility of ectopic pregnancy.

Failure of IVF treatment

This is the most common complication of treatment. The likely reasons for this failure are cancelled cycles (approximately 10% of treatment cycles will be abandoned before egg collection), failure to collect eggs (about 1%), failure of fertilization (about 5%), and failure of implantation (this could be due to defective embryo or endometrium, or poor synchronization).

A significant portion of normal embryos are chromosomally abnormal and this proportion increases with advanced maternal age.

The IVF (in-vitro fertilization) procedure is considered by some, to be one of the most stressful infertility treatments. Failure of treatment can result in emotional strain, psychological stress and depression. Some couples may require psychological counseling. In addition, couples may encounter psychological difficulties if a multiple pregnancy occurs.

There is no drug that is absolutely safe and completely free of side effects. The fertility drugs that stimulate ovulation are rarely associated with complications. There are potential problems, which may occur and include: side effects of fertility drugs, ovarian hyperstimulation syndrome (OHSS), multiple pregnancy, adnexal torsion (ovarian twisting) and the risk of ovarian cancer.

Multiple pregnancy

In the majority of patients, fewer than 20% of the embryos are implanted after embryo transfer to the uterus, so two or more embryos are usually replaced which results in high-order multiple pregnancies.

Although the prospect of twin or triplets may seem attractive to some couples, high order of multiple pregnancies is associated with increased risks of maternal and fetal complications. In addition, multiple pregnancies place enormous strains for the parents including financial difficulties, emotional distress and physical exhaustion.

If all twins, triplets, and quads were born as healthy as singletons there would not be any concerns. Unfortunately, multiple pregnancies have much higher risks than singletons for the fetuses and also for the mother. The risk of these complications arising must be balanced against the number of embryos transferred and the corresponding increase in success rate.

Maternal risks associated with multiple pregnancy

• Miscarriage
• Hemorrhage
• Pregnancy induced high blood pressure
• Pre-eclampsia occurs three to five times more frequently
• Diabetes
• Anemia
• Polyhydramnios (excessive amounts of amniotic fluid that surrounds the fetus)
• Caesarean section is often needed in twin pregnancy, and almost always required for triplets or more
• Prolonged hospitalization resulting in higher cost of medical care

Fetal complications associated with multiple pregnancy

• Preterm delivery. The average length of a pregnancy is 39 weeks for a single pregnancy, 35 weeks for twins and 33 for triplets. Preterm delivery occurs over 50% in twin pregnancy and in 90% of triplets. The proportion of twins and triplets delivering before 30 weeks pregnancy is around 7% and 15% respectively. These babies are more likely to suffer serious, lifelong, health problems, such as cerebral palsy and disability. The risk per pregnancy of producing a child with cerebral palsy is 8 times greater in twin pregnancies and 47 times greater in triplet pregnancies than in singleton pregnancies.
• Multiple pregnancies have a four-fold increase in the rate of low birth weight compared to single pregnancy. The risk of lifelong disability is over 25% for babies weighing less than 1 Kg.
• Stillbirth rates and neonatal death rates are higher for multiple pregnancies compared to singletons. For example, for a single birth the incidence is less than 1%, for twins 4.7% and for triplets 8.3%.
• Birth defects are twice as common as in single birth.

Ovarian hyperstimulation syndrome (OHSS)

This is the most serious complication of IVF. Any patient undergoing ovulation induction is at risk of developing OHSS, although some more than others. Ovarian hyperstimulation syndrome may be classified as mild, moderate or severe by symptoms and signs. the worst cases seem tends to be associated with pregnancy. Severe OHSS is a life threatening complication following ovarian stimulation.

The symptoms usually begin 4-5 days after the egg collection. The majority of women have a mild or moderate form of the syndrome and invariably resolve within a few days unless pregnancy occurs, that may delay recovery. Patient may complain of pain, a bloated feeling and mild abdominal swelling. In a small proportion of women, the degree of discomfort can be quite pronounced.

In some cases cysts appear in the ovaries (ovarian cysts) and fluid may collect in the abdominal cavity causing discomfort.

Very rarely the ovarian hyperstimulation is severe and the ovaries are very swollen. The woman will feel ill, with nausea and vomiting, abdominal pain. Fluid accumulates in the abdominal cavity and chest, causing abdominal swelling and shortness of breath. Reduction in the amount of urine produced. These complications require urgent hospital admission to restore the fluid and electrolyte balance, monitor progress, control pain and in some very serious cases, termination of pregnancy. Complications associated with severe OHHS include blood clotting disorders, kidney damage and twisted ovary (ovarian torsion).

Incidence of OHSS

Despite careful monitoring, up to 33% of IVF treatment have been reported to be associated with mild forms of OHSS. Severe OHSS has been reported in 3-8% of IVF cycles

Causes of OHSS

Over response to fertility drugs. Cause is unknown. But, women at risk of developing OHHS include.

• Women with polycystic ovaries. There is evidence that adding metformin to ovulation induction in women with PCOS undergoing IVF treatment reduces the risk of developing OHSS (Tang et al. Human Reproduction 2006)
• Young thin women.
• High estrogen hormone levels and a large number of follicles or eggs.
• Administration of GnRh agonist.
• The use of hCG for luteal phase support.

Management and treatment options for OHSS

• Withhold hCG administration when the blood estrogen levels and ultrasound scans show a high risk of severe OHHS.
• Proceed with egg collection, inseminate the eggs but have any viable embryos frozen and not proceed to fresh embryo transfer in that cycle and undergo subsequent frozen embryo transfer treatment cycle. Concentrated human albumin may be given intravenously at the time of egg collection to reduce symptoms of OHSS.
• Coasting to stop the gonadotropin stimulation and continuing the agonist suppression until estrogen levels declines to acceptable levels before proceeding to egg collection.
• Cabergoline 0.5 mg tablet daily starting on the day of HCG injection and continue for 8 days have been shown to reduce the risk of severe OHSS

Risks of egg collection

As with any surgical procedure, there are potential risks associated with egg collection. Such risks depend on whether the egg collection is performed by vaginal ultrasound or laparoscopy.

Vaginal ultrasound egg collection

• Mild to moderate discomfort.
• Bleeding during or after egg collection from the ovary or from the top of the vagina, the bleeding is usually minimal and is very rarely a problem. The need for blood transfusion is rare (about 1 in 500).
• Infection is also a rare complication, the risk is about 1 in 300, and can be treated with antibiotics.
• Injuries to internal organs such as bowels, bladder or blood vessels during the procedure. This is an extremely rare complication (about 1 in 1000).

Laparoscopic egg collection

Laparoscopic egg collection has similar complications to those described above, but the risk of injury to internal organs is higher than after ultrasound scan. In addition, there is risk of complications associated with the use of a general anesthetic, although this is rare in healthy women.

Ectopic Pregnancy

One of the potential risks of fertility treatments such as In-Vitro Fertilisation (IVF) and Intrauterine Insemination (IUI) is the increased chance of ectopic pregnancy. Ectopic pregnancy occurs when a woman's egg is fertilised by her partner's sperm and the resulting embryo implants somewhere outside the woman's womb. When an embryo grows outside the womb, a potentially life-threatening situation is created for both mother and foetus. Health statistics show that approximately 1 % of all pregnancies are ectopic. Although ectopic pregnancies can occur also when a woman conceives naturally, fertility treatments such as IVF or IUI increase a fertility patient's chances of her pregnancy being ectopic.

In a normal pregnancy, a woman's ovary releases an egg which travels down her fallopian tube on the way to her womb. On its way, the egg is fertilised by a man's sperm to create an embryo. The embryo then finishes its journey as described above and implants in the womb, where, hopefully, a healthy baby will grow over the course of the next nine months. According to NHS statistics, in 95 % of ectopic pregnancies, the embryo remains in the fallopian tube - although ectopic pregnancy can occur in the cervix (the neck of the womb), the ovary and the abdominal cavity. The danger is that the affected organ will rupture and cause severe bleeding. Very few ectopic pregnancies actually result in the death of the mother. Generally, an embryo cannot survive an ectopic pregnancy and therefore treatment nearly always requires the removal of the embryo. Even if the ectopic pregnancy is not treated the embryo will probably not survive, although the decision not to treat the ectopic pregnancy is a highly risky one for the mother.

During IVF treatment, a woman's eggs are removed directly from her ovaries and are fertilised with her partner's sperm outside her body (in a laboratory). The resulting embryos are then inserted directly into her womb. Given that most ectopic pregnancies occur when a fertilised egg gets stuck in the fallopian tube, you might ask how IVF could possibly increase the chances of ectopic pregnancy, since IVF "bypasses" the fallopian tubes altogether. Fertility specialists believe that ectopic pregnancy may occur if, when the embryos are transferred to the womb, they are placed too high in the womb cavity. The embryos then have a greater chance of "wandering" and implanting themselves in places where they are not supposed to be, such as the fallopian tubes. Embryos could also make their way into the fallopian tubes if they are injected into the womb with too much force. In the past, doctors would block the fallopian tubes during IVF treatment to try and prevent ectopic pregnancy from occurring. This method is no longer used.