What are the Risks of IVF Treatment?

What are the Risks of IVF Treatment?

In vitro Fertilization treatment represent commonly utilized management strategies for infertility with multifactorial causes (including genetically predisposed diseases). IVF treatment may predispose the mother to increased risks and complications during treatment period and pregnancy, and also there may be adverse fetal outcomes. You can read the information below about the maternal and fetal risks and safety of IVF treatment.

Short Term Risks of IVF Treatment

These risks can be observed during that treatment cycle or just after the end of the treatment.

1- Medication side effects

During the ovulation induction part of the IVF treatment, injectable fertility medications are used to stimulate the ovaries to develop multiple eggs. Short term risks of IVF treatment are generally due to medication side effects. A very few numbers of women might have some reaction to the medications used during IVF and mostly, these side effects are mild. They may include:

  • Nausea
  • Soreness or bruising from Injections
  • Breast tenderness
  • Bloating
  • Mood Swings: Feeling down or irritable, Restlessness
  • Fatigue
  • Allergic Reactions
  • Mild pelvic and abdominal pain
  • Hot flushes
  • Headaches

2- Egg-retrieval procedure complications

After the hormone treatment to stimulate the ovaries to produce more eggs, the eggs are retrieved. The egg retrieval procedure takes place about 36 hours after the injection of human chorionic gonadotropin (hCG),which signals the follicles to prepare to ovulate. 

The egg retrieval procedure is a minor surgery done under anesthesia and generally lasts about 10-15 minutes. It is done on an outpatient basis, and the woman usually goes home a few hours later. Both the surgery and the anesthesia can carry potential risks, but the rate of complications is very low.

In a study in Germany that examined the outcome of approximately 380,000 oocyte retrieval surgeries reported  vaginal bleeding in 0.07 percent of the women, intra-abdominal bleeding in 0.05 percent, intestinal injuries in 0.001 percent, and peritonitis, or an inflammation of the peritoneum (the lining of the abdominal cavity) in 0.005 percent. Of all the women who had the procedure, only 0.002 percent—2 in every 100,000—had complications that required surgery to correct.

Some women may feel worse the first few days after retrieval than they feel on the day of it, some reporting menstrual-type cramping, while others have bloating and abdominal discomfort. After about 5-7 days, the ovaries go back to their original size and most people feel better at that point.

3- Ovarian Hyperstimulation Syndrome (OHSS)

Normally, a mild stimulation of the ovaries in a controlled manner is desired during the IVF procedure. However, sometimes a picture known as ovarian hyperstimulation syndrome (OHSS) may occur with the accumulation of fluid in the abdomen and enlargement of the ovaries because of moderate or severe stimulation of the ovaries. OHSS is a frequently encountered problem especially in ovulation induction of women with PCOS. In women with OHSS, swelling and pain in abdomen, nausea, vomiting, increased thirst symptoms are observed. Rarely seen in severe forms, the excess fluid can result in difficulty breathing and decreased urination.

Long term risks of IVF treatment include

1- Ectopic pregnancy

Tubal disease and history of pelvic infection are the main risk factors identified for ectopic pregnancy in IVF population. The risk of ectopic pregnancy is 3–5-fold and heterotopic pregnancy is at least 30 times higher than in natural conception. The risk of tubal pregnancy reduces following embolization or removal of Fallopian tubes in women with hydrosalpinxes. The main risk factors for ectopic pregnancy in general population are pelvic infection, tubal disease, endometriosis, previous tubal surgery, age > 35 years, and smoking. It is estimated that tubal factors account for 14% of the causes of subfertility in women. Undiagnosed tubal damage among subfertile women with ectopic pregnancies who underwent IVF has also been reported.

2- Early pregnancy complications

The risk of early pregnancy bleeding in women who conceive following IVF treatment is four times more. It is possible that the increased risk is related to increased level of anxiety among women who conceived following IVF with the resulting increase in the number of hospital visits.

3- Miscarriage

Currently, there is not enough evidence to suggest that the risk of miscarriage is increased following IVF treatment. There is no difference in the incidence of chromosomal abnormalities between the miscarriages of following either IVF or intracytoplasmic sperm injection (ICSI) treatment or natural conception.

4- Multiple births

IVF increases the risk of multiple births if more than one embryo is transferred to uterus. Multiple pregnancy has a more complicated pregnancy outcome that may increase the risk of gestational hypertension, gestational diabetes, pre-eclampsia, increased rate of cesarean section, anemia, and hemorrhage during delivery, than mothers of single babies.

Multiple pregnancies can seriously harm the health of the babies also. At least half of twins are born premature and underweight, which can lead to serious (in some cases, long-term) health problems and even death. Also, far more likely to have an early or late miscarriage.

Which preventive measures reduce the risk of having a multiple birth?

Elective single embryo transfer (eSET). This means that only one embryo is transferred instead of two or three. Any remaining embryos can be frozen for to use in follow up treatment. Having an eSET has no significant impact on success rates. However, it may not be suitable for everyone, particularly older women.

5- Adverse Obstetrical, Fetal and Neonatal Outcomes

While most IVF-conceived children are healthy, research have focused mainly on the risk of obstetric complications and fetal outcomes in IVF-conceived pregnancies. Some studies suggested an association between IVF treatment and an increased risk of adverse obstetric and perinatal outcomes including hypertensive disorders of pregnancy, preterm labor and preterm delivery, and low birth weight. IVF pregnancies have also been associated with congenital anomalies, imprinting disorders, and neurodevelopmental disorders. Many of these outcomes can be attributed to an increased risk of multiple gestations with IVF or infertility is a risk factor for congenital anomalies given the equal rate of anomalies recorded in infertile patients conceiving spontaneously.

Hypertensive Disorders of Pregnancy

Hypertensive disorders of pregnancy include gestational hypertension, preeclampsia, and eclampsia. Studies show that having a hypertensive disorder of pregnancy in IVF/ICSI is higher than unassisted conceptions.

The association between hypertensive disorders of pregnancy in IVF is difficult to ascertain given that women pursuing IVF may be older and may have other comorbidities such as obesity, polycystic ovary syndrome (PCOS).

Gestational diabetes (GDM)

An increased incidence of GDM in pregnancies conceived via IVF has been demonstrated. A meta-analysis analyzing 13,399 IVF/ICSI patients showed a relative risk of GDM of 1.48. This data suggests an increased incidence of GDM in the IVF population in singleton pregnancies.

The increased risk may be because women tend to be older when seeking infertility treatment and therefore at higher risk for GDM due to advancing age or they may have polycystic ovary syndrome (PCOS) which increases the risk of GDM. Some studies suggest that the infertility diagnosis itself may confer risk.

Preterm Delivery (<37 weeks)

There appears to be an increased risk of preterm delivery in children conceived after IVF. The studies indicate that IVF procedures may be contributing to the risk of preterm delivery in singleton gestations, but that the risk may be lessened in the setting of frozen/thawed embryo transfers. Some of the risk factors for preterm delivery such as older maternal age and behavioral factors such as smoking may account for some of the risks seen in patients with infertility.

Low Birth Weight (<2500g)

An increased risk of low birth weight has been associated among children conceived with the assistance of IVF/ICSI compared to those conceived without medical assistance. The association between IVF/ICSI conception and low birth weight may be due to the supraphysiological hormonal environment of the IVF cycle. Maternal subfertility itself may contribute to the risk of having a child that is of low birthweight.

A retrospective cohort study evaluating births after 95,991 fresh and 16,521 frozen/thawed embryo transfer cycles showed a lower incidence of low birth weight after frozen/thawed embryo transfer cycles compared to fresh IVF cycles, but also a higher incidence of high birth weight after frozen/thawed embryo transfer cycles.

Birth defects

The effect of assisted reproduction procedures on the health of children born using IVF is not fully understood and infertility is a risk factor for congenital anomalies given the equal rate of anomalies recorded in infertile patients conceiving spontaneously. Some studies focusing on birth defects among children after IVF report that infants conceived with the use of IVF was associated with an increased risk for birth defects compared to those conceived naturally while on the other hand most of the studies published until now show no statistically significant differences in the rates of anomalies between babies born after IVF/ICSI transfer and infertile patients conceiving spontaneously without any treatment.

Are IVF Babies At Higher Risk Of Birth Defects? ►

6- Psychological disturbance

IVF is physically and emotionally stressful. The anxiety levels and depression increase in mothers who had experienced two or more treatment cycles and in women with unsuccessful IVF treatments. On the other hand, successful treatment was also found to be associated with increased levels of anxiety in comparison with women who conceived spontaneously. Women who became pregnant after IVF treatment were more anxious about the survival and normality of their unborn babies, damage to their babies during childbirth or separating from their babies after birth. It is, therefore, sensible to conclude that IVF couples may need additional emotional support during their treatment and in pregnancy.

7- Do the drugs used in IVF treatment have cancer-causing effects?

Concerns exist regarding long-term risks of fertility medications causing cancer, since despite their multiple modes of action, all can induce multiple ovulations and alter hormone production. Some cancers, including female reproductive and breast cancers, are hormone dependent. On the other hand, infertility per se is a risk factor for certain cancers including those of the breast, ovary, and uterus.

Studying cancer risk in infertile couples has several challenges. Some conditions, including anovulation, endometriosis and nulliparity accompany infertility and themselves increase the risk of cancer. Additionally, most of these cancers are rare and tend to occur several years after the time of fertility treatment, making proof of causal relationship difficult.

Overall, most studies show that fertility treatments do not increase the risks of invasive ovarian cancer, malignant melanoma or cancers of the endometrium, cervix, breast, thyroid or colon.

Regarding cancer, there is no evidence to suggest a direct cause relationship between IVF treatment and cancer regardless of the number of treatment cycles or the type of fertility drugs used. The risk of cancer may be elevated in IVF women because of the women's characteristics including their subfertility status.

In summary, there are a few potential risks to mothers who conceive through IVF. Most of these risks, however, are related to the woman's subfertility status and/or increased incidence of multiple pregnancy. Women undergoing IVF treatment are at increased risk of anxiety and depression about their treatment outcome.

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